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THE DRUGS AND COSMETICS RULES, 1945
as corrected up to the 30th November, 2004
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DEPARTMENT OF HEALTH NOTIFICATION
New Delhi, the 21st December 1945
No. F. 28-10/45-H (1). __In exercise of the powers conferred by Sections 6(2), 1[12, 33 and 33N] of the Drugs and Cosmetics Act, 1940 (XXIII of 1940), the Central Government is pleased to make the following Rules: __
RULES
PART I__PRELIMINARY
1. Short title, extent and commencement. ___(1) These Rules may be called the Drugs and
Cosmetics Rules, 1945. 2(2) They extend to the whole of India.
2. Definitions.___ In these Rules, unless there is anything repugnant in the subject or context___ (a)“the Act” means the Drugs and Cosmetics Act, 1940 (XXIII of 1940) as amended
from time to time; 3(b)“Central Licence Approving Authority” means the Drugs Controller, India,
appointed by the Central Government.
(c)“Director” means the Director of the Central Drugs Laboratory;
(d) “From” means a form set forth in Schedule A; 4(dd)Homoeopathic medicines include any drug which is recorded in
Homoeopathicproving or therapeutic efficacy of which has been established through long clinical experience as recorded in authoritative Homoeopathic literature of India and abroad and which is prepared according to the techniques of Homoeopathic pharmacy and covers combination of ingredients of such Homoeopathic medicines but does not include a medicine which is administered by parenteral route.
(e) “Laboratory” means the Central Drugs Laboratory;
1Amended by G.O.I. Notification No.G.S.R. 370(E) dated 07-04-1994 2Amended by G.O.I Notification No.G.S.R. 358 dated 15-3-1975 (Govt. of India Notification No. X 11011/3/72-D & MS dated 5-3-1975). 3Amended by G.O.I. Notification No. G.S.R. 923(E) dated 14-12-1992 4Added under Government of India Notification No. F. 1-59 / 68-D, dated 19th Nov. 1969.
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1[(ea) “registered Homeopathic medical practitioner” means a person who is registered in the Central Register or State Register of Homeopathy;]
2[(ee) “Registered medical practitioner” means a person__
(i)holding a qualification granted by an authority specified or notified under Section 3 of the Indian Medical Degrees Act, 1916 (7 of 1916), or specified In the Schedules to the Indian Medical Council Act, 1956 (102 of 1956); or
(ii) registered or eligible for registration in a medical register of a State meant for the registration of persons practicing the modern scientific system of medicine 3excluding the Homoeopathic system of medicine; or
(iii) registered in a medical register, 3other than a register for the registration of Homoeopathic practitioner, of a State, who although not falling within sub- clause (i) or sub-clause (ii) declared by a general or special order made by the State Government in this behalf as a person practicing the modern scientific system of medicine for the purposes of this Act; or
(iv) registered or eligible for registration in the register of dentists for a State under the Dentists Act, 1948 (16 of 1948); or
(v) who is engaged in the practice of veterinary medicine and who possesses qualification approved by the State Government.
4(f)‘retail sale’ means a sale 5[whether to a hospital, or dispensary, or a medical, educational or research institute or to any other person] other than a sale by way of wholesale dealing;
5(g) ‘sale by way of wholesale dealing’ means sale to a person for the purpose of selling again and includes sale to a hospital, dispensary, medical, educational or research institution.
________________________________________________________ 1Ins by G.O.I Notification No. G.S.R 680 (E) dated 5-12-1980 2Added by Government of India, Notification No. F. 1-22 / 59-D, dated 9 th April, 1960. 3Amended by S. O. No. 2139 dated 12-8-1972 (Govt. of India Notification No. X. 11014/12/72-D, dated the 5 th June, 1972). 4Amended or added under Government of India Notification No. F. 1-3/51-DS., Dated 15 th October, 1954. 5Amended by G.O.I. Notification No. G.S.R 681 (E) dated 6-6-1988
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1(h) “Schedule” means a Schedule to these Rules.
2(i)State Government in relation to a Union Territory means the Administrator thereof.
(j)‘Poisonous substance’ means a substance specified in Schedule E.
PART II___THE CENTRAL DRUGS LABORATORY
3. Functions. ____It shall be the function of the Laboratory___
(i)to analyse or test such samples of drugs as may be sent to it under sub-section (2) of Section 11, or under sub-section (4) of Section 25 of the Act;
(ii) 2* * *
(iii) to carry out such other duties as may be entrusted to it by the Central Government or, with the permission of the Central Government, by a State Government after consultation with the Drugs Technical Advisory Board.
33A(1)The functions of the Laboratory in respect of the following drugs or classes of drugs shall be carried out at the Central Research Institute, Kasauli, and the functions of the Director in respect of the said drugs or classes of drugs shall be exercised by the Director of the said Institute :___
(1) Sera
(2) Solution of serum proteins intended for injection
(3) Vaccines
(4) Toxins
(5) Antigens
(6) Anti-toxins
(7) Sterilized surgical ligature and sterilized surgical suture.
(8) Bacteriophages.
1Amended by Government of India Notification No. F.28-10/45-H (1), dated 31st March 1957. 2Amended or omitted by Government of India Notification No. F-1-16/57-D, dated 15th June, 1957. 3Amended by Government of India Notification No. F. 4-1 / 60-D, dated 15th May, 1961
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1[Provided that the functions of the Director in respect of Oral Polio Vaccine shall be exercised by the Deputy Director and Head of the Polio Vaccine Testing Laboratory in case of Central Research Institute, Kasauli only.]
2[(1A) The functions of the Laboratory in respect of Oral Polio Vaccine shall be carried out by the following Institutes and the functions of the Director in respect of the said drugs shall be exercised by Director of the respective Institutes :--
(a)Pasteur Institute of India, Coonoor. (b) Enterovirus Research Centre (Indian Council of Medical Research), Haffkin Institute
Compound, Parel, Bombay-400012.] 3[(c) The National Institute of Biologicals, NOIDA.]
4(2) The functions of the Laboratory in respect of the following drugs or classes of drugs shall be carried out at the Indian Veterinary Research Institute, Izatnagar or Mukteshwar and the functions of the Director in respect of the said drugs or classes of drugs shall be exercised by the Director of either of the said institutes.
(1) Anti-sera for veterinary use.
(2) Vaccines for veterinary use.
(3) Toxoids for veterinary use.
(4) Diagnostic Antigens for veterinary use. 5(3) The functions of the laboratory in respect of condoms shall be carried out at the Central
Indian Pharmacopoeia Laboratory, Ghaziabad, and the functions of the Director in respect of the said condoms shall be exercised by the Director of the said Laboratory.
6[(4) The functions of the Laboratory in respect of the following drug shall be carried out at the Laboratory of the Serologist and Chemical Examiner to the Government of India, Calcutta and the functions of the Director in respect of the said drug shall be performed by the Serologist and Chemical Examiner of the said Laboratory :__
VDRL Antigen.
________________________________________________________________ 1 Ins. by G.O.I.Notification No. G.S.R.62(E) dt 15.02.1982 and amended by notification no.G.S.R.445(E) dated 30-04-1992 2Added by Notification No.G.S.R. 445(E) dated 30-04-1992 3Amended by Notification No. G.S.R.249(E) dated 04-04-2002 4Amended by Govt. of India, Ministry of Health, F P&W.H. & U.D. Notification No. F.-1-6/62-D, dated the 2 nd July, 1969. 5Amended by S. O. No. 2139 dated 12-8-1972 (Govt. of India Notification NO. X. 11014/12/72-D, dated the 5 th June, 1972). 6 Sub rule (4) omitted and subrule (5) renumbered as (4) by G.O.I. by Notification No. G.S.R. 62(E) dated 15-02-1982
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1[(5) The function of the Laboratory in respect of Intra-Utrine Devices and falope Rings shall be carried out at the Central Drug Testing Laboratory, Thane, Maharashtra and the functions of the Director in respect of the said devices shall be exercised by the Director of the said Laboratory.]
2[(6) The functions of the Laboratory in respect of human blood and human blood products including components, to test for freedom of HIV antibodies, shall be carried out by the following Institutes, Hospitals and the functions of the Director in respect of the above mentioned products shall be exercised by the head of the respective Institutes, namely:--
(a) National Institutes of Communicable Disease, Department of Microbiology, Delhi. (b) National Institute of Virology, Pune (c) Centre of Advanced Research in Virology, Christian Medical College, Vellore.]
3[(7) The functions of the Laboratory in respect of Homoeopathy shall be carried out at the Homoeopathy Pharmacopoeia Laboratory, Ghaziabad and the function of the director in respect of the Homeopathic medicine shall be exercised by the Director of the laboratory.]
4[(8) The functions of the Laboratory in respect of Blood Grouping reagent and diagnostic kits for Human Immunodeficiency Virus, Hepatitis B Surface Antigen and Hepatitis C Virus shall be carried out at the National Institute of Biologicals, NOIDA and the functions of the Director in respect of the said drugs shall be exercised by the Director of the said laboratory.]
4. Despatch of samples for test or analysis. __ (1) Samples for test or analysis under sub- section (4) of Section 25 of the Act shall be sent by registered post in a sealed packet, enclosed, together with a memorandum in Form 1, in an outer cover addressed to the Director.
(2)The packet as well as the outer cover, shall be marked with a distinguishing number.
(3)A copy of the memorandum in Form 1 and a specimen impression of the seal used to seal the packet shall be sent separately by registered post to the Director.
5. Recording of condition of seals. __ On receipt of the packet, it shall be opened by an officer authorized in writing in that behalf by the Director who shall record the condition of the seal on the packet.
_________________________________________________________________ 1Ins by G.O.I. Notification GSR No. 865 (E) dt 25.10.1990 and subs. by G.O.I. Notification No. G.S.R 242(E) dated 18-03-1998 2Ins. By G.O.I. Notification No. G.S.R 16(E) dated 10-01-1990
3Ins. by G.O.I. Notification No. G.S.R 246(E) dated 1-5-1991 4 Ins. by G.O.I. Notification G.S.R. No.249(E) dated 04.04.2001
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6. Report of result of test or analysis. __ After test or analysis the result of the test or analysis, together with full protocols of the tests applied, shall be supplied forthwith to the sender in Form 2.
7. Fees. __ The fees for test and analysis shall be those specified in Schedule B.
8. Signature of certificates. __ Certificates issued under these Rules by the Laboratory shall be signed by the Director or by an officer authorized by the Central Government by notification in the official Gazette to sign such certificates.
1PART III (Rules 9 to 20)
PART IV ___IMPORT 2[AND REGISTERATION]
21. In this Part____ 4[(a)“import licence” means a licence in Form 10 to import drugs 3* * *; excluding
those specified in Schedule X, or a licence in Form 10-A to import drugs specified in Schedule X.]
(b)“licensing authority” means the authority appointed by the Central Government to perform the duties of the licensing authority under these Rules and includes any person to whom the powers of a licensing authority may be delegated under Rule 22;
(c)“licence for examination, test or analysis” means a licence in Form 11 to import small quantities of drugs the import of which is otherwise prohibited, for the purpose of examination, test or analysis.
2[(d) “manufacturer” includes a manufacturer of drugs, who may be a Company or a unit or a body corporate or any other establishment in a country other than India, having its drug manufacturing facilities duly approved by the National Regulatory Authority of that country, and who also has a free sale approval of the drugs approved by the said authority in the concerned country, and /or in other major countries:
(e)”Registration Certificate” means a certificate issued under rule 27A by the licensing authority in Form 41 for registration of the premises and the drugs manufactured by the manufacturer meant for import into and use in India.]
22.The licensing authority may with the approval of the Central Government by an order in writing delegate the power to sign licences and 2[Registration Certificate and] such other powers as may be specified in the order to any other person under his control. ___________________________________________________________
1Omitted by Government of India Notification No. F. 1-16/57-D, dated 15 th June, 1957. 2 Ins. by G.O.I. Notification No. G.S.R 604(E) dated 24-08-2001 3Omitted by G.O.I. Notification No. G.S.R 604(E) dated 24-08-2001 4 Subs. By Govt of India Notification no.462 (E) dt.22.06.1982
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1[23.Import licences .__ An import licence in Form 10 shall be required for the import of 2drugs, excluding those specified in Schedule X, and an import licence in Form 10 A shall be required for the import of drugs specified in Schedule X.]
2[24 Form and manner of application for import licence. __ (1) An application for an import licence shall be made to the licensing authority in Form 8 for drugs excluding those specified in Schedule X, and in Form 8-A for drugs specified in Schedule X, either by manufacturer himself having a valid wholesale licence for sale or distribution of drugs under these rules, or by the manufacturer’s agent in India either having a valid licence under the rules to the manufacture for sale of a drug or having a valid wholesale licence for sale or distribution of drugs under these rules, and shall be accompanied by a licence fee of one hundred rupees for a single drug and an additional fee at the rate of one thousand rupees for each additional drug and by an undertaking in Form 9 duly signed by or on behalf of the manufacturer:
Provided that in the case of any subsequent application made by the same importer for import licence for drugs manufactured by the same manufacturer, the fee to accompany each such application shall be one hundred rupees for each drug.
(2) Any application for import licence in Form 8 or Form 8-A, as the case may be, shall be accompanied by a copy of Registration Certificate issued in Form 41 under rule 27-A:
Provided that in case of emergencies the licensing authority may, with the approval of the Central Government, issue an import licence in Form 10 or 10-A, as the case may be, without the issuance of Registration Certificate under rule 27-A, for reasons to be recorded in writing.”
(3) A fee of two hundred and fifty rupees shall be paid for a duplicate copy of the licence issued under this rule, if the original is defaced, damaged or lost.
24-A. Form and manner of application for Registration Certificate. — (1) An application for issue of a Registration Certificate shall be made to the licensing authority in Form 40, either by the manufacturer himself, having a valid whole sale licence for sale or distribution of drugs under these rules, or by his authorized agent in India, either having a valid licence under the rules to manufacture for sale of a drug or having a valid whole sale licence for sale or distribution of drugs under these rules, and shall be accompanied by the fee specified in sub-rule (3) and the informations and undertakings specified in Schedules D-I and D-II duly signed by or on behalf of the manufacturer.
1Subs. By G.O.I. Notification No. G.S.R 462(E) dated 22-06-1982 2Amended by Notification No. G.S.R 604(E) dated 24-08-2001
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(2) The authorization by the manufacturer of his agent in India shall be documented by a power of attorney executed and authenticated either in India before a First Class Magistrate, or in the country of origin before such an equivalent authority, the certificate of which is attested by the Indian Embassy of the said country, and the original of the same shall be furnished along with the application for Registration Certificate.
(3) (i) A fee of one thousand and five hundred US dollars shall be paid alongwith the application in Form 40 as registration fee for his premises meant for manufacturing of drugs intended for import into and use in India
(ii) A fee of one thousand US dollars shall be paid along with the application in Form 40 for the registration of a single drug meant for import into and use in India and an additional fee at the rate of one thousand US dollars for each additional drug.
Provided that in the case of any subsequent application for registration of additional drugs by the same manufacturer, the fee to accompany shall be one thousand US dollars for each drug.
(4)The fees shall be paid through a Challan in the Bank of Baroda, Kasturba Gandhi Marg, New Delhi-110001 or any other branch or branches of Bank of Baroda, or any other bank, as notified, from time to time, by the Central Government, to be credited under the Head of Account “0210-Medical and Public Health, 04-Public Health, 104-Fees and Fines”:
Provided that in the case of any direct payment of fees by a manufacturer in the country of origin, the fees shall be paid through Electronic Clearance System (ECS) from any bank in the country of origin to the Bank of Baroda, Kasturba Gandhi Marg, New Delhi, through the Electronic Code of the bank in the Head of Account “0210-Medical and Public Health, 04- Public Health, 104- Fee and Fines”, and the original receipt of the said transfer shall be treated as an equivalent to the bank challan, subject to the approval by the Bank of Baroda that they have received the payment.”
(5) The applicant shall be liable for the payment of a fee of five thousand US dollars for expenditure as may be required for inspection or visit of the manufacturing premises or drugs, by the licensing authority or by any other persons to whom powers have been delegated in this behalf by the licensing authority under rule 22:
(6) The applicant shall be liable for the payment of testing fees directly to a testing laboratory approved by the Central Government in India or abroad, as may be required for examination, tests and analysis of drug.
(7) A fee of three hundred US dollars shall be paid for a duplicate copy of the Registration Certificate, if the original is defaced, damaged or lost.
(8) No Registration Certificate shall be required under these rules in respect of an inactive bulk substance to be used for a drug formulation with or without pharmacopoeal conformity.]
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25.Licences for import of drugs manufactured by one manufacturer___ (1) A single application may be made, and a single licence may be issued, in respect of the
import of more than one drug or class of drugs manufactured by the same manufacturer:
1Provided that the drugs or classes of drugs are manufactured at one factory or more than one factory functioning conjointly as a single manufacturing unit;
Provided further that if a single manufacturer has two or more factories situated in different places manufacturing the same or different drugs a separate licence shall be required in respect of the drugs manufactured by each such factory.
(2) 2 * * *
325A.Condition to be satisfied before a licence in Form 10 or Form 10-A is granted.___ (1) A licence in Form 10 or in Form 10-A shall be granted by the licensing authority having
regard to--
(i) the premises, where the imported substances will be stocked are equipped with proper storage accommodation for preserving the properties of the drugs to which the licence applies; and
(ii) the occupation, trade or business ordinarily carried out by the applicant;
Provided that the licensing authority may refuse to grant a licence in Form 10-A in respect of any applicant where he is satisfied,--
(a) that the applicant has not complied with the provisions of the Act or these rules or (b) that by reasons of—
4[(i) his conviction under the Act or these rules or the Narcotic Drugs and Psychotropic Substances Act, 1985 (61 of 1985) or the rules made thereunder.]
(ii) previous suspension or cancellation of the licence granted to him; he is not a fit person to whom licence shall be granted.
(2)Any person who is aggrieved by the order passed by the licensing authority under this rule may, within thirty days of the receipt of the order, appeal to the Central Government and the Central Government may after such enquiry in to the matter as it considers necessary and after giving the appellant an opportunity for making a representation in the matter, make such orders in relation thereto as it thinks fit.
1Added under Government of India Notification No. F. 1-19/48-D, dated 27 th October, 1949. 2Added or omitted under Government of India Notification No.F. 1-16/57-D, dated 15th June, 1957. 3Subs. by G.O.I. Notification No. G.S.R 462(E) dated 22-06-1982 4Subs. by G.O.I. Notification No. G.S.R 604(E) dated 24-08-2001
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1[25B. Registration Certificate for import of drugs manufactured by one manufacturer:--(1) A single application may be made, and a single Registration Certificate in Form 41 may be issued in respect of the import of more than one drug or class of drugs, manufactured by the same manufacturer:
Provided that the drug or classes of drugs, are manufactured at one factory or more than one factory functioning conjointly as a single manufacturing unit:
Provided further that if a single manufacturer has two or more factories situated in different places manufacturing the same or different drugs, separate Registration Certificates shall be required in respect of the drugs manufactured by each such factory.]
26. Conditions of import licence. ____An import licence shall be subject to the following conditions:
(i) the manufacturer shall at all times observe the undertaking given by him or on his behalf in Form 9;
(ii) the licensee shall allow any Inspector authorized by the licensing authority in that behalf to enter with or without notice any premises where the imported substance is stocked, to inspect the means, if any, employed for testing the substance and to take samples;
(iii) the licensee shall on request furnish to the licensing authority from every batch of each substance or from such batch or batches as the licensing authority may from time to time specify a sample of such amount as the licensing authority may consider adequate for any examination required to be made, and the licensee shall, if so required, furnish full protocols of the tests, if any, which have been applied.
(iv) if the licensing authority so directs the licensee shall not sell or offer for sale any batch in respect of which a sample is or protocols are furnished under the last preceding subrule until a certificate authorizing the sale of the batch has been issued to him by or on behalf of the licensing authority;
(v) the licensee shall, on being informed by the licensing authority that any part of any batch of the substance has been found by the licensing authority not to conform with the standards of strength, quality and purity prescribed by Chapter III of the Act, or the Rules thereunder and on being directed so to do withdraw the remainder of that batch from sale and, so far as may in the particular circumstances of the case be practicable, recall the issues already made from that batch;
1 Ins. by G.O.I. Notification G.S.R.No.604(E) dated 24.08.2001
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(vi) the licensee shall maintain a record of all sales by him of substances for the import of which a licence is required, showing particulars of the substance and of the person to whom sold and such further particulars, if any, as the licensing authority may specify and such record shall be open to the inspection of any Inspector authorised in that behalf by the licensing authority;
1[ Provided that in respect of the sale or distribution of drugs specified in Schedule X, the licensee shall maintain separate record or register showing the following particulars, namely;
1. Name of the Drug, 2. Batch number, 3. Name and address of the manufacturer, 4. Date of transaction, 5. Opening stock on the business day, 6. Quantity of drug received, if any, and the source from which received, 7. Name of the purchaser, his address and licence number, 8. Balance quantity of drug at the end of the business day, 9. Signature of the person under whose supervision the drugs have been supplied]
(vii)the licensee shall comply with such further requirements, if any, applicable to the holders of import licenses, as may be specified in any Rules, subsequently made under Chapter III of the Act and of which the licensing authority has given to him not less than four months’ notice.
27.Grant of import licence. ____On receipt of an application for an import licence in the form and manner prescribed in Rule 24, the licensing authority shall, on being satisfied that, if granted, the conditions of the licence will be observed, issue an import licence in Form 10 1[or From 10-A, as the case may be.]
2[27-A Grant of Registration Certificate:-- (1) On receipt of an application for Registration Certificate in the Form and manner specified in rule 24-A, the licensing authority shall, on being satisfied, that, if granted, the conditions of the Registration Certificate will be observed, issue a Registration Certificate in Form 41:
Provided further that if the application is complete in all respects and informations specified in Schedules D-1 and D-11 are in order, the licensing authority shall, within nine months from the date of receipt of an application, issue such Registration Certificate, and in exceptional circumstances and for reasons to be recorded in writing, the Registration Certificate may be issued within such extended period, not exceeding three months as the licensing authority, may deem fit. ______________________________________________________________
1Amended by Notification No. G.S.R 462(E) dated 22-06-1982 2Inserted by Notification No. G.S.R 604(E) dated 24-08-2001
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(2) If the applicant does not receive the Registration Certificate within the period as specified in the proviso to sub rule (1), he may appeal to the Central Government and the Central Government may after such enquiry into the matter, as it considers necessary, may pass such orders in relation thereto as it thinks fit.]
128. Duration of import licence. __A licence unless, it is sooner suspended or cancelled, shall be valid 2[for a period of three years from the date of its issue]
Provided that if application for a fresh licence is made three months before the expiry of the existing licence the current licence shall be deemed to continue in force until orders are passed on the application.
328-A. Duration of Registration Certificate. - A Registration Certificate, unless, it is sooner suspended or cancelled, shall be valid for a period of three years from the date of its issue:
Provided that if the application for a fresh Registration Certificate is made nine months before the expiry of the existing certificate, the current Registration Certificate shall be deemed to continue in force until orders are passed on the application.
29. Suspension and cancellation of import licence. __ If the manufacturer or licensee fails to comply with any of the conditions of an import licence, the licensing authority may after giving the manufacturer or licensee an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefore, suspend or cancel it for such period as it thinks fit, either wholly or in respect of some of the substances to which it relates:
4[Provided that a person who is aggrieved by the order passed by the licensing authority under this rule may, within thirty days of the receipt of the order, appeal to the Central Government, and the Central Government may, after such enquiry into the matter, as it considers necessary and after giving the said appellant an opportunity for representing his views, pass such orders in relation thereto as it thinks fit.]
3[29-A. Suspension and cancellation of Registration Certificate. —If the manufacturer fails to comply with any of the conditions of the Registration Certificate, the licensing authority may after giving him an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefore, suspend or cancel the Registration Certificate for such period as it thinks fit either wholly or in respect of some of the substances to which it relates: ______________________________________________________________
1Amended by Government of India Notification No. F. 1-10/62-D, dated 19th April, 1964. 2Amended by G.O.I. Notification No. G.S.R 604(E) dated 24-08-2001
3Inserted by G.O.I. Notification No. G.S.R 604(E) dated 24-08-2001 4Subs. by G.O.I.Notification No. G.S.R 604(E) dated 24-08-2001
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Provided that a person, who is aggrieved by the order passed by the licensing authority under this rule may, within thirty days of the receipt of the order, appeal to the Central Government, and the Central Government may, after such enquiry into the matter as it considers necessary and after giving the appellant an opportunity for representing his views in the matter, pass such orders in relation thereto as it thinks fit.]
30. Prohibition of import after expiry of potency. —No biological or other special product specified in Schedule C or C (1) shall be imported after the date shown on the label, wrapper or container of the drug as the date up to which the drug may be expected to retain a potency not less than, or not to acquire a toxicity greater than, that required, or as the case may be, permitted by the prescribed test.
1* * * * *
30AA.Import of New Homoeopathic medicine: __
(1) No new Homoeopathic medicine shall be imported except under and in accordance with the permission in writing of the Licensing Authority.
(2) The importer of a New Homoeopathic medicine when applying for permission shall produce before the Licensing Authority such documentary and other evidence as may be required by the Licensing Authority for assessing the therapeutic efficacy of the medicine including the minimum provings carried out with it.
2[Explanation. —For the purpose of this rule, ‘New Homoeopathic Medicine’ means— (i) a Homoeopathic medicine which is not specified in the Homoeopathic
Pharmacopoeia of India or United States of America or of the United Kingdom or the German Homoeopathic Pharmacopoeia; or
(ii) which is not recognized in authoritative Homoeopathic literature as efficacious under the conditions recommended; or
(iii)a combination of Homoeopathic medicines containing one or more medicines which are not specified in any of the Pharmacopoeias referred to in clause (i) as Homoeopathic medicines and also not recognized in authoritative Homoeopathic literature as efficacious under the conditions recommended.]
330-B. Prohibition of import of certain drugs. ___ No drug, the manufacture, sale or distribution of which is prohibited in the country of origin, shall be imported under the same name or under any other name except for the purpose of examination, test or analysis.
_________________________________________________________________ 1 Section 30A omitted by G.O.I. Notification No. G.S.R. 944 (E) dated 21-09-1998. 2Amended as per G.O.I. Notification No. G.S.R. 680(E) dated 5-12-1980 3Amended under Government of India Notification No. F. 1-45 4th January, 1951
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1[31. Standard for certain imported drugs. —No drug shall be imported unless it complies with the standard of strength, quality and purity, if any, and the test prescribed in the rules shall be applicable for determining whether any such imported drug complies with the said standard:
Provided that the drugs intended for veterinary use, the standards of strength, quality and purity, if any, shall be those that are specified in Schedule F (1) and the test prescribed in that Schedule shall be applicable for determining whether any such imported drug complies with the said standards and where no standards are specified in Schedule F(1) for any veterinary drug, the standards for such drug shall be those specified in the current edition, for the time being in force, of the British Pharmacopoeia Veterinary:
Provided further that the licensing authority shall not allow the import of any drug having less than sixty percent residual shelf-life period as on the date of import:
Provided also that in exceptional cases the licensing authority may, for reasons to be recorded in writing, may allow, the import of any drug having lesser shelf-life period, but before the date of expiry as declared on the container of the drug.]
232.Packing and labeling of imported drugs. __No drug shall be imported unless it is packed and labeled in conformity with the rules in Parts IX and X 3* * * and further conform to the standards laid down in Part XII provided that in the case of drugs intended for veterinary use, the packing and labeling shall conform to the rules in Parts IX and X and Schedule F(1).
432-A Packing and Labelling of Homoeopathic medicine.--No Homoeopathic medicine shall be imported unless it is packed and labeled in conformity with the rules in Part IX-A
33. Import of drugs for examination, test or analysis.____ Small quantities of drugs the import of which is otherwise prohibited under Section 10 of the Act may be imported for the purpose of examination, test or analysis subject to the following conditions:__
a) No drug shall be imported for such purpose except under a licence in form 11;
b) the licensee shall use the substances imported under the licence exclusively for purposes of examination, test or analysis and shall carry on such examination, test or analysis in the place specified in the licence, or in such other places as the licensing authority may from time to time authorize;
________________________________________________________________________ 1Substituted as per G.O.I. Notification No.G.S.R. 604 (E) dated 24-08-2001 2Amended by Govt. of India, Ministry of Health, F. P. & W. H. & U. D. Notification No. F. 1-6/62-D.
dated 2-7-1969. 3Omitted under G.O.I. Notification No. G.S.R.663(E) dated 3-7-1992 4Amended by S. O. No. 2139 dated 12-8-1972 (Govt of India Notification No. X. 11014/12/72-D, dated the
5th June, 1972).
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c) the licensee shall allow any Inspector authorized by the licensing authority in this behalf to enter, with or without prior notice, the premises where the substances are kept, and to inspect the premises, and investigate the manner in which the substance are being used and to take samples thereof;
d) the licensee shall keep a record of, and shall report to the licensing authority, the substances imported under the licence, together with the quantities imported, the date of importation and the name of the manufacturer;
e) the licensee shall comply with such further requirements, if any applicable to the holders of licences for examination, test or analysis as may be specified in any rules subsequently made under Chapter III of the Act and of which the licensing authority has given to him not less than one month’s notice.
1[33-A Import of drugs by a Government Hospital or Autonomous Medical Institution for the treatment of patient.—Small quantities of new drug, as defined in rule 122-E, the import of which is otherwise prohibited under this section 10 of the Act, may be imported for treatment of patients suffering from life threatening diseases, or diseases causing serious permanent disability, or such disease requiring therapies for unmet medical needs, by a Medical Officer of a Government Hospital or an Autonomous Medical Institution providing tertiary care, duly certified by the Medical Superintendent of the Government Hospital, or Head of the Autonomous Medical Institution, subject to the following conditions, namely:-
(a) no new drug shall be imported for the said purpose except under a licence in Form 11-A, and the said drug has been approved for marketing in the country of origin;
(b) the licence shall use the substances or drugs imported under the licence exclusively for the purpose of treatment of patients suffering from life threatening diseases, or diseases causing serious permanent disability, or such diseases requiring therapies for unmet medical needs, under the supervision of its own Medical Officers at the place, specified in the licence or at such other places, as the licensing authority, may from time to time authorize;
(c) the licencee shall allow an Inspector authorised by the licensing authority in this behalf to enter, with or without prior notice, the premises where the substances or drugs are stocked, and to inspect the premises and relevant records and investigate the manner in which the substances or drugs are being used and to take, if necessary, samples thereof ;
(d) the licencee shall keep a record of, and shall submit the said report half yearly to the licensing authority, the substances or drugs imported under the licence, together with the quantities imported and issued to the patients, the date of importation, the name of the manufacturer, the name and address of the patient for whom the drug is prescribed and the name of disease;
____________________________________________________________ 1Inserted by G.O.I.Notification No. G.S.R 604(E) dated 24-08-2001
68
(e) the licencee shall comply with such other requirements, if any, applicable to the holders of import licences for import of new drugs for treatment of patients by Government Hospitals, as may be specified from time to time in any rule subsequently made under Chapter 111 of the Act and of which the licensing authority has given to him not less than one month’s notice;
(f)the drug shall be stocked under proper storage conditions and shall be dispensed under the supervision of a registered pharmacist;
(g) the quantity of any single drug so imported shall not exceed 100 average dosages per patient:
Provided that the licensing authority may, in exceptional circumstances, sanction the import of drug a large quantity.]
34. Application for licence for examination, test or analysis.____(1) An application for a licence for examination, test or analysis shall be made in Form 12 and shall be made or countersigned by the head of the institution in which, or by a proprietor or director or the company or firm by which the examination, test or analysis will be conducted.
(2)The licensing authority may require such further particulars to be supplied as he may consider necessary.
1[(3) Every application in Form 12 shall be accompanied by a fee of one hundred rupees for a single drug and an additional fee of fifty rupees or each additional drug.
(4) The fees shall be paid through a challan in the Bank of Baroda, Kasturba Gandhi Marg, New Delhi-110001 or any other branch or branches of Bank of Baroda, or any other Bank, as notified, from time to time, by the Central Government, to be credited under the Head of Account 0210-Medical and Public Health, 04- Public Health, 104- Fees and Fines.]
2[34-A. Application for licence to import small quantities of new drugs by a Government Hospital or Autonomous Medical Institution for the treatment of patients.—(1) An application for an import licence for small quantities of a new drug, as defined in rule 122-E for the purpose of treatment of patients suffering from life threatening diseases, or diseases causing serious permanent disability, or such diseases requiring therapies for unmet medical needs, shall be made in Form 12-AA, by a Medical Officer of the Government Hospital or Autonomous Medical Institution, which shall be certified by the Medical Superintendent of the Government Hospital or Head of the Autonomous Medical Institution, as the case may be.
___________________________________________________________________________ 1Substituted by Notification No. G.S.R 604(E) dated 24-08-2001 2 Inserted by G.O.I.Notification No. G.S.R 604(E) dated 24-08-2001
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(2) The licensing authority may require such further particulars to be supplied, as he may consider necessary.
(3) Every application in Form 12-AA shall be accompanied by a fee of one hundred rupees for a single drug and an additional fee of fifty rupees for each additional drug.
(4) The fees shall be paid through a challan in the Bank of Baroda, Kasturba Gandhi Marg, New Delhi-110001 or any other branch or branches of Bank of Baroda, or any other Bank, as notified, from time to time, by the Central Government, to be credited under the Head of Account 0210- Medical and Public Health, 04- Public Health, 104- Fees and Fine.]
35. Cancellation of licence for examination, test or analysis.___(1) A licence for examination, test or analysis may be cancelled by the licensing authority for breach of any of the conditions subject to which the licence was issued.
(2) A licensee whose licence has been cancelled may appeal to the Central Government within three months of the date of the order
1[35A. Cancellation of licence for import of small quantities of new drugs.--(1) A licence for import of small quantities of a new drug, defined in rule122-E, for the purpose of the treatment of patients suffering from life threating diseases, or diseases causing serious permanent disability, or such diseases requiring therapies for unmet medical needs, by a Government Hospital or an Autonomous Medical Institution may be cancelled by the licensing authority for breach of any of the conditions subject to which the licence was issued or for contravention of any of the provisions of the Act and rules made thereunder.
(2) A licencee whose licence has been cancelled may appeal to the Central Government within three months from the date of the receipt of the order, and the Central Government may after such enquiry into the matter, as it considers necessary and after giving the appellant an opportunity for representing his views, may pass such orders in relation thereto, as it thinks fit.]
36. Import of drugs for personal use.__ Small quantities of drugs, the import of which is otherwise prohibited under Section 10 of the Act, may be imported for personal use subject to the following conditions: __
(i) the drugs shall form part of a passenger’s bona fide baggage and shall be the property of, and be intended for, the exclusive personal use of the passenger;
(ii) the drugs shall be declared to the Customs authorities if they so direct; (iii) the quantity of any single drug so imported shall not exceed one hundred average
doses : _________________________________________________________________
1Inserted by G.O.I.Notification No. G.S.R 604(E) dated 24-08-2001
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Provided that the licensing authority may in an exceptional case in any individual case sanction the import of a large quantity:
1Provided further that any drug, imported for personal use but not forming part of bona fide personal baggage, may be allowed to be imported subject to the following conditions, namely:--
(i)the licensing authority, on an application made to it in Form 12-A is satisfied that the drug is for bona fide personal use;
(ii)the quantity to be imported is reasonable in the opinion of the licensing authority and is covered by prescription from a registered medical practitioner ; and
(iii) the licensing authority grants a permit in respect of the said drug in Form 12-B.
237. Packing of patent or proprietary medicine. —Patent or proprietary medicines shall be imported in containers intended for retail sale.
3Provided that such medicines may be imported in bulk containers by any person who holds a licence to manufacture, if such person has obtained permission in writing to import such medicines from the licensing authority at least three months prior to the date of import and the imports are made within a period of twelve months from the date of issue of such permission.
38. Statement to accompany imported drugs. ___ All consignments of drugs sought to be imported shall be accompanied by an invoice or other statement showing the name and address of the manufacturer and the name and quantities of the drugs.
39. Documents to be supplied to the Customs Collector. ___Before drugs for the import of which a licence is not required are imported a declaration signed by or on behalf of the manufacturer or by or on behalf of the importer that the drugs comply with the provisions of Chapter III of the Drugs and Cosmetics Act, 1940 and the Rules thereunder shall be supplied to the Customs Collector.
440. Procedure for the import of drugs. ____(1) If the Customs Collector has reason to doubt whether any drugs comply with the provisions of Chapter III of the Act and Rules thereunder he may, and if requested by an officer appointed for this purpose by the Central Government shall, take samples of any drugs in the consignment and forward them to the Director of the laboratory appointed for this purpose by the Central Government and may detain the drugs in the consignment of which samples have been taken until the report of the Director of the said laboratory or any other officer empowered by him on this behalf, subject to the approval of the Central Government, on such samples is received :
____________________________________________________________________________ 1Amended under Government of India Notification No.F-1-36/54-D.S.,dated 3rd March,1955. 2Amended under Government of India Notification No.F-1-3/51-D.S.,dated 15th October,1954 3Amended under Government of India Notification No.F-1-45/58-D, dated 4th January,1961 4Amended by the Government of India Notification No. F. 1-99/52-D.S., dated 3rd November, 1953
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Provided that if the importer gives an undertaking in writing not to dispose of the drugs without the consent of the Customs Collector and to return the consignment or such portion thereof as may be required, the Customs Collector shall make over the consignment to the importer.
(2) If an importer who has given an undertaking under the proviso to sub-rule (1) is required by the Customs Collector to return the consignment or any portion thereof he shall return the consignment or portion thereof within ten days of receipt of the notice.
141. (1) If the Director of the laboratory appointed for the purpose by the Central Government or any other officer empowered by him on this behalf, subject to the approval of the Central Government, reports to the Customs Collector that the samples of any drug in a consignment are not of standard quality, or that the drug contravenes in any other respect the provisions of Chapter III of the Act or the Rules thereunder and that the contravention is such that it cannot be remedied by the importer, the Customs Collector shall communicate the report forthwith to the importer who shall, within two months of his receiving the communication either export all the drugs of that description in the consignment, to the country in which they were manufactured or forfeit them to the Central Government which shall cause them to be destroyed :
Provided that the importer may within fifteen days of receipt of the report make a representation against the report to the Customs Collector, and the Customs Collector shall forward the representation with a further sample to the licensing authority, who after obtaining, if necessary, the report of the Director of the Central Drugs Laboratory, shall pass orders thereon which shall be final.
2(2) If the Director of the laboratory appointed for the purpose by the Central Government or any other officer empowered by him on this behalf, subject to the approval of the Central Government reports to the Customs Collector that the samples of any drug contravene in any respect the provisions of Chapter III of the Act or the Rules thereunder and that the contravention is such that it can be remedied by the importer, the Customs Collector shall communicate the report forthwith to the importer and permit him to import the drug on his giving an undertaking in writing not to dispose of the drug without the permission of the officer authorized in this behalf by the Central Government.
42. 3* * * _________________________________________________________________
1Amended by Government of India Notification No. F. 7-7/47-D, dated 5th January, 1954 2Added under Government of India Notification No. 7-11/47-D, dated 5th October, 1951. 3Omitted by Government of India Notification No. F. 1-9/52-DS., dated 3rd November, 1953
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43. The drugs specified in Schedule D shall be exempt from the provisions of Chapter III of the Act and of the Rules made thereunder to the extent, and subject to the conditions specified in that Schedule.
1[43A. No drug shall be imported into India except through one of the following places, namely: __
Freozepore Cantonment and Amritsar Railway Stations:
In respect of drugs imported by rail across the frontier with Pakistan.
Ranaghat, Bongaon and Mohiassan Railways Stations:
In respect of drugs imported by rail across the frontier with Bangladesh
2[Raxaul: In respect of drugs imported by road and railway lines connecting Raxaul in India and Birganj in Nepal]
3[Chennai, Kolkata, Mumbai and Cochin, Nhava Sheva and Kandla]:
In respect of drugs imported by sea into India.
4[Chennai, Kolkata, Mumbai, Delhi, Ahemdabad and Hyderabad]:
In respect of drugs imported by sea into India.
543-B.Drugs, consignments of which are in transit through India to foreign countries and which shall not be sold or distributed in India shall be exempted from the requirements of Chapter III of the Drugs and Cosmetics Act, 1940 (23 of 1940) and the rules made thereunder.
Provided that if the Government of the countries to which the drugs are consigned regulate their import by the grant of import licences, the importer shall at the time of import into India, produce such import licences.
_________________________________________________________________ .
1 Subs. by G.O.I. Notification No. G.S.R 478(E) dated 6th August, 1981 2Ins. by G.O.I.Notification No. G.S.R 120(E) dated 05-03-1998 3Amended by Notification No. G.S.R 504(E) dated 18-07-2002 (Also, the word Calcutta substituted with a word ‘Kolkata’ as per this notification).
4Amended by Notification No. G.S.R 647(E) dated 28-10-1998 5Added under Government of India Notification No. E. 1-60/D, dated 19th March, 1964.
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PART V—1[GOVERNMENT ANALYSTS, INSPECTORS, LICENCING AUTHORITIES AND CONTROLLING AUTHORITIES]
244. Qualifications of Government Analyst. ____ A person appointed as a Government Analyst under the Act shall be a person who____
(a) is a graduate in medicine or science or pharmacy or pharmaceutical chemistry of a 4[University established in India by law or has an equivalent qualification recognized by the Central Government for such purpose] and has had not less than five years’ post-graduate experience in the testing of drugs in a laboratory under control of (i) a Government Analyst appointed under the Act, or (ii) the head of an Institution or testing laboratory approved for the purpose by the appointing authority, 3[ or has completed training on testing of drugs, including items stated in Schedule C, in Central Drugs Laboratory], or
(b) possesses a post-graduate degree in medicine or science or pharmacy or Pharmaceutical chemistry of a 4[University established in India by law or has an equivalent qualification recognized by the Central Government for such purpose]or possesses the Associateship Diploma of the Institution of Chemists (India) obtained by passing the said examination with “Analysis of Drugs and Pharmaceuticals’ as one of the subjects and has had after obtaining the said post-graduate degree or diploma not less than three years’ experience in the testing of drugs in a laboratory under the control of (i) a Government Analyst appointed under the Act, or (ii) the head of an Institution or testing laboratory approved for the purpose by the appointing authority 3[or has completed training on testing of drugs, including items stated in Schedule C, in Central Drugs Laboratory];
Provided that- 3[(i) for purpose of examination of items in Schedule C, --
(ia) the persons appointed under clause (a) or (b) and having degree in Medicine, Physiology, Pharmacology, Microbiology, Pharmacy should have experience or training in testing of said items in an institution or laboratory approved by the appointing authority for a period of not less than six months;
(ib) the person appointed under clause(a) or (b) but not having degree in the above subjects should have experience or training in testing of said Schedule C drugs for a period of not less than three years in an institution or laboratory approved by the appointing authority or have completed two years training on testing of drugs including items stated in Schedule C in Central Drugs Laboratory;]
_____________________________________________________________________________ 1 Subs. by G.O.I. Notification No. G.S.R 443(E) dated 12-04-1989 2Amended by G.S.R. No. 1427 dated 22-10-77 (Govt. of India Notification No. X. 11013/2/76-D & MS dated the 10th October, 1977) 3Ins. by G.O.I. Notification No. G.S.R 697(E) dated 26-10-1995 4.Subss. by G.O.I. Notification No. G.S.R.71(E) dated30.01.1987
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(ii) for a period of four years from the date on which Chapter IV of the Act takes effect in the States, persons whose training and experience are regarded by the appointing authority as affording, subject to such further training, if any, as may be considered necessary, a reasonable guarantee of adequate knowledge and competence, may be appointed as Government Analysts. The persons so appointed may, if the appointing authority so desires, continue in service after the expiry of the said period of four years :
(iii) no person who is engaged directly or indirectly in any trade or business connected with the manufacture of drugs shall be appointed as a Government Analyst for any area :
Provided further that for the purpose of examination of Anti-sera, Toxoid and Vaccines and Diagnostic Antigens for Veterinary use, the person appointed shall be a person who is a graduate in Veterinary Science, or general science, or medicine or pharmacy and has had not less than five years’ experience in the standardization of biological products or person holding a post-graduate degree in Veterinary Science, or general science, or medicine or pharmacy or pharmaceutical chemistry with an experience of not less than three years in the standardization of biological products :
Provided also that persons, already appointed as Government Analysts may continue to remain in service, if the appointing authority so desires, notwithstanding the fact that they do not fulfil the qualifications as laid down in clause (a), clause (b) or the preceding proviso.
45. Duties of Government Analysts. __(1) The Government Analyst shall cause to be analysed or tested such samples or drugs 1and cosmetics as may be sent to him by Inspectors or other persons under the provisions of Chapter IV of the Act and shall furnish reports of the results of test or analysis in accordance with these Rules.
(2)A Government Analyst shall from time to time forward to the Government reports giving the result of analytical work and research with a view to their publication at the discretion of Government.
46. Procedure on receipt of sample. On receipt of a package from an Inspector containing a sample for test or analysis, the Government Analyst shall compare the seals on the packet 2[or on portion of sample or container] with the specimen impression received separately and shall note the condition of the seals on the 2[packet or on portion of sample or container]. After the test or analysis has been completed, he shall forthwith supply to the Inspector a report in triplicate in Form 13 of the result of the test or analysis, together with full protocols of the tests or analysis applied: __________________________________________________________________________ 1Ins. by G.O.I. Notification No. S.O. 2139 dt 12.8.1972 2 Ins./ Subs. by G.O.I. Notification No. GSR 59(E) dt 7.2.1995.
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1Explanation.____It shall be deemed to be full and sufficient compliance with the requirement of the rule in respect of the supply of “protocols of the tests or analysis applied”, if____
(1) for pharmacopoeial drug, where the tests or methods of analysis prescribed in the official pharmacopoeia are followed, references to the specific tests or analysis in the pharmacopoeias are given in the report;
(2)for patent or proprietary medicines for which the tests and methods prescribed in any of the official pharmacopoeias are applicable and are followed, references to the specific tests or analysis in the pharmacopoeias are given in the report;
(3)for patent or proprietary medicines containing pharmacopoeial drugs for which the official tests or analysis or methods of assays are modified and applied, a description of the actual tests or, as the case may be, analysis or methods of assays so applied is given in the report;
(4) for patent or proprietary medicines for which no pharmacopoeial tests or methods of analysis are available or can be applied but for which tests or methods of analysis given in standard books or journals are followed, a description of such tests or methods of analysis applied together with the reference to the relevant books or journals from which the tests or methods of analysis have been adopted, is given in the report;
(5) for those drugs for which methods of test are not available and have been evolved by the Government Analyst, a description of tests applied is given in the report.
47. Report of result of test or analysis. ___ An application from a purchaser for test or analysis of a drug under Section 26 of the Act shall be made in Form 14 A and the report of test or analysis of the drug made on such application shall be supplied to the applicant in Form 14-B.
48. Fees. ___ The fees to be paid by a person submitting to the Government Analyst under Section 26 of the Act for test or analysis of a drug purchased by him shall be those specified in Schedule B.
2[49. Qualifications of Inspectors. —A person who is appointed an Inspector under the Act shall be a person who has a degree in Pharmacy or Pharmaceutical Sciences or Medicine with specialisation in clinical Pharmacology or Microbiology from a University established in India by law:
Provided that only those Inspectors: --
__________________________________________________________________________ 1Ins. under Government of India Notification No. F. 1-60/61-D, dated 12th July, 1962. 2Substituted by G.O.I. Notification No. G.S.R 658(E) dated 19-10-1993
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(i) Who have not less than 18 months’ experience in the manufacture of atleast one of the substances specified in Schedule C, or
(ii) Who have not less than 18 months’ experience in testing of atleast one of the substances in Schedule C in a Laboratory approved for this purpose by the licensing authority, or
(iii) Who have gained experiences of not less than three years in the inspection of firms manufacturing any of the substances specified in Schedule C during the tenure of their services as Drugs Inspector; shall be authorised to inspect the manufacture of the substances mentioned in Schedule C.]
1[Provided further that the requirement as to the academic qualification shall not apply to the persons appointed as Inspectors on or before the 18th day of October, 1993.]
2[ 49A. Qualification of a Licensing Authority.—
No person shall be qualified to be a Licensing Authority under the Act unless:-- (i) he is a graduate in Pharmacy on Pharmaceutical Chemistry or in Medicine with
specialization in clinical pharmacology or microbiology from a University established in India by law; and
(ii) he has experience in the manufacture or testing of drugs or enforcement of the provisions of the Act for a minimum period of five years:]
3[ Provided that the requirements as to the academic qualification shall not apply to those inspectors and the Government Analysts who were holding those positions on the 12th day of April,1989.
450.Controlling authority.__(1) All Inspectors appointed by the Central Government shall be under the control of an officer appointed in this behalf by the Central government.
(2) All Inspectors appointed by the State Government shall be under the control of an officer appointed in this behalf by the State Government.
(3) For the purposes of these rules an officer appointed by the Central Government under sub-rule (1), or as the case may be, an officer appointed by the State Government under sub-rule (2), shall be a controlling authority.
__________________________________________________________________________ 1 Ins. by G.O.I. by Notification No. G.S.R 552(E) dated 04-12-1996 2 Ins. by G.O.I. Notification No. GSR 443(E) dt 12.4.1989. 3 Sub. By G.O.I. Notification No. GSR 532 (E) dt 14.8.1991. 4. Amended by G.O.I. Notification No. S.O. 2139 dt 12.8.1972.
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1[50A. Qualification of a Controlling Authority.—
(1) No person shall be qualified to be a controlling Authority under the Act unless.-- (i) he is a graduate in Pharmacy or Pharmaceutical Chemistry or in Medicine with
specialization in clinical Pharmacology or microbiology from a University established in India by law and
(ii)he has experience in the manufacture or testing of drugs or enforcement of the provisions of the Act for a minimum period of five years:
2[Provided that the requirements as to the academic qualifications shall not apply to those Inspectors and the Government Analysts who were holding those positions on the 12th day of April, 1989.]
51. Duties of Inspectors of premises licensed for sale.___ Subject to the instructions of the controlling authority, it shall be duty of an Inspector authorized to inspect premises licensed for the sale of drugs____
(1) to inspect 3[not less than once a year] all establishments licensed for the sale of drugs within the area assigned to him;
(2) to satisfy himself that the conditions of the licences are being observed;
(3) to procure and send for test or analysis, if necessary, imported packages which he has reason to suspect contain drugs being sold or stocked or exhibited for sale in contravention of the provisions of the Act or Rules thereunder;
(4) to investigate any complaint in writing which may be made to him;
(5) to institute prosecutions in respect of breaches of the Act and Rules thereunder;
(6) to maintain a record of all inspections made and action taken by him in the performance of his duties, including the taking of samples and the seizure of stocks, and to submit copies of such record to the controlling authority;
(7) to make such enquiries and inspections as may be necessary to detect the sale of drugs in contravention to the Act;
__________________________________________________________________ 1 IIns. by G.O.I.Notification No. G.S.R 443(E) dated 12-04-1989 2Subs. by Notification No. G.S.R 532(E) dated 14-8-1991 3Subs. by G.O.I. Notification GSR 700 (E) dt 28.9.2001.
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(8) when so authorized by the State Government, to detain imported packages which he has reason to suspect contain drugs, the import of which is prohibited.
52.Duties of Inspectors specially authorized to inspect the manufacture of 1[drugs or cosmetics].__ Subject to the instructions of the controlling authority it shall be the duty of an Inspector authorized to inspect the manufacture of drugs____
(1) to inspect 2[not less than once a year], all premises licensed for manufacture of 1[drugs or cosmetics] within the area allotted to him to satisfy himself that the conditions of the licence and provisions of the Act and Rules thereunder are being observed;
(2) in the case of establishments licensed to manufacture products specified in Schedule C and C(1) to inspect the plant and the process of manufacture, the means employed for standardizing and testing the 2[drugs or cosmetics], the methods and place of storage, the technical qualifications of the staff employed and all details of location, construction and administration of the establishment likely to affect the potency or purity of the product;
(3) to send forthwith the controlling authority after each inspection a detailed report indicating the conditions of the licence and provisions of the Act and Rules thereunder which are being observed and the conditions and provisions, if any, which are not being observed.
(4) to take samples of the 1[drugs or cosmetics] manufactured on the premises and send them for test or analysis in accordance with these Rules;
(5) to institute prosecutions in respect of breaches of the Act and Rules thereunder.
53. Prohibition of disclosure of information.___ Except for the purposes of official business or when required by a Court of Law, an Inspector shall not, without the sanction in writing of his official superior, disclose to any person any information acquired by him in the course of his official duties.
54. Form of order not to dispose of stock.-- An order in writing by an Inspector under clause (c) of Section 22 of the Act requiring a person not to dispose of any stock in his possession shall be in Form 15.
__________________________________________________________________ 1Amended by G.O.I. Notification No. G.S.R 504(E) dated 18-07-2002 2Amended by G.O.I. Notification No. G.S.R 700(E) dated 28-9-2001
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154-A.Prohibition of sale.__ No person in possession of a 2[drug or cosmetic] in respect of which an Inspector has made an order under clause (c) of sub-section (i) of Section 22 of the Act shall in contravention of that order sell or otherwise dispose of any stock of such 2[drug or cosmetic].
355. Forms of receipts for seized drug, cosmetic, record register, document or any other material object.-- A receipt by an Inspector for the stock of any drug or cosmetic or for any record, register, document or any other material object seized by him under clause (c) or clause (cc) of sub-section (1) of Section 22 of the Act shall be in Form 16.
4 [55A . Manner of certifying copies of seized documents.—The Drugs Inspector shall return the documents , seized by him under clause (cc) or produced before him under clause (cca), of sub-section (1) of section 22 of the Act, within a period of twenty days of the date of such seizure or production, to the person from whom they have seized or, as the case may be, the person who produced them, after copies thereof extracts therefrom have been singed by the concerned Drug Inspector and the person from whom they have seized , or, as the case may be , who produced such records.]
56.Form of intimation of purpose of taking samples.__ When an Inspector takes a sample of a drug for the purpose of test or analysis, he shall intimate such purpose in writing in Form 17 to the person from whom he takes it.
5[56A . Form or receipt for samples of drugs where fair price tendered is refused.—Where the fair price, for the samples of drugs taken for the purpose of test or analysis, tendered under sub-section (1) of section 23 has been refused, the Inspector shall tender a receipt therefor to the person from whom the said samples have been taken as specified in Form 17-A;]
57. Procedure for dispatch of sample to Government Analyst.__(1) The portion of sample or the container sent by an Inspector to the Government Analyst for test or analysis under sub- section (4) of Section 23 of the Act shall be sent by registered post or by hand in a sealed packet, enclosed together with a memorandum in Form 18, in an outer cover addressed to the Government Analyst.
(2)A copy of the memorandum and a specimen impression of the seal used to seal the packet shall be sent to the Government Analyst separately by registered post or by hand. __________________________________________________________________
1Added under G.O.I. Notification No. F. 1-19/59-D, dated 13 th June, 1961. 2Amended by G.O.I. Notification No. G.S.R 850(E) dated 07-12-1994 3Amended by GSR No. 926 dated 16-7-1977 (Govt. of India Notification No. X. 11014/6/76-D & MS dated 24-6-1977). 4Inserted by G.O.I. Notification No. G.S.R 89(E) dated 16-2-1981 5Inserted by G.O.I. Notification No. G.S.R 292(E) dated 29-5-1997
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158. Confiscation of drugs, implements, machinery etc.____
1) Where any person has been convicted for contravening any of the provisions of Chapter IV of the Act or any rule made thereunder, the stock of the drug in respect of which the contravention has been made shall be liable to confiscation.
2) Where any person has been convicted for the manufacture of any drug deemed to be misbranded under clause (a), clause (b), clause (c), clause (d), clause (f) or clause (g) of section 17 of the Act, or adulterated drug under section 17 B of the Act, or for manufacture for sale, or stocking or exhibiting for sale or distribution of any drug without a valid licence as required under clause (c) of section 18 of the Act, any implements or machinery used in such manufacture, sale or distribution and any receptacle, packages, or coverings in which such drug is contained and the animals, vehicles, vessels or other conveyances used in carrying such drug shall also be liable to confiscation.
258-A. Procedure for disposal of confiscated drugs.____(1) The Court shall refer the confiscated drugs to the Inspector concerned for report as to whether they are of standard quality or contravene the provisions of the Act or the Rules in any respect.
(2) If the Inspector, on the basis of Government Analyst’s report finds the confiscated drugs to be not of standard quality or to contravene any of the provisions of the Act or the Rules made thereunder, he shall report to the Court accordingly. The Court shall thereupon order the destruction of the drugs. The destruction shall take place under the supervision of the Inspector in the presence of such authority, if any, as may be specified by the Court.
(3) If the Inspector finds that the confiscated drugs are of standard quality and do not contravene the provisions of the Act or the Rules made thereunder, he shall report to the Court accordingly. 3[The Court may then order the Inspector to give the stocks of confiscated drugs to hospital or dispensary maintained or supported by the Government or by Charitable Institution.]
__________________________________________________________________ 1Amended by S. O. No. 289, dated 3-2-1973 ( G.O.I. Notification No. X. 11014/17/72__D, dated the 20th December, 1972).
2Added under G.O.I. No. F. 1-9/62-D, dated 2nd Dec. 1964. 3 Subs. by G.O.I. Notification No. GSR 59(E) dt 7.2.1995.
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PART VI ____ SALE OF DRUGS OTHER THAN HOMOEOPATHIC
MEDICINES
59. (1) The State Government shall appoint Licensing Authorities for the purpose of this Part for such areas as may be specified.
1(2) Applications for the grant or renewal of a licence 2[to sell, stock, exhibit or offer for sale or distribute] drugs, other than those included in Schedule X, 3[shall be made in Form 19 accompanied by a fee of rupees one thousand and five hundred or Form 19-A. accompanied by a fee of rupees five hundred, as the case may be, or in the case of drugs included in Schedule X shall be made in Form 19-C accompanied by a fee of rupees five hundred, to the licensing authority:]
Provided that in the case of an itinerant vendor or an applicant who desires to establish a shop in a village or town having population of 5,000 or less, the application in Form 19-A shall be accompanied by a fee of rupees ten .
(3)3[A fee of rupees one hundred and fifty] shall be paid for a duplicate copy of a licence 4[to sell, stock, exhibit or offer for sale or distribute] drugs, other than those included in Schedule X, or for a licence 4[ to sell, stock, exhibit or offer for sale or distribute] drugs, included in Schedule X, if the original is defaced, damaged or lost;
Provided that in the case of itinerant vendor or an applicant who desires to established a shop in a village or town having a population of 5,000 or less, the fee for a duplicate copy of a licence if the original is defaced, damaged or lost, shall be rupees two.
(4) Application for renewal of a licence 4[to sell, stock, exhibit or offer for sale or distribute] drugs, after its expiry but within six months of such expiry 3[shall be accompanied by a fee of rupees one thousand and five hundred plus an additional fee at the rate of rupees five hundred per month or part thereof in Form 19, rupees five hundred plus an additional fee at the rate of rupees two hundred fifty per month or part thereof in Form 19-A and rupees five hundred plus an additional fee at the rate of rupees two hundred and fifty per month or part thereof in Form 19- C:]
Provided that in the case of an itinerant vendor or an applicant desiring to open a shop in a village or town having a population of 5,000 or less the application for such renewal shall be _________________________________________________________________
1Substituded by G.O.I. Notification No. G.S.R 462(E) dated 22-6-1982 2Amended by G.O.I. Notification No. G.S.R 778(E) dated 10-10-1985 3Amended by G.O.I. Notification No. G.S.R 601(E) dated 24-08-2001 4 Subs. by G.O.I. Notification No. GSR 778(E) dt 10.1.1985.
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accompanied by a fee of rupees ten, plus an additional fee at the rate of rupees eight per month or part thereof.]
160. A licensing authority may with the approval of the State Government by an order in writing delegate the power to sign licences and such other powers as may be specified in the order to any other person under his control.
2[61. Forms of licences to sell drugs. __ (1) a licence 3[ to sell, stock, exhibit or offer for sale or distribute] drugs other than those specified in Schedule C, C (1) and X and by retail on restricted licence or by wholesale, shall be issued in Form 20, Form 20-A or Form 20 –B, as the case may be:
Provided that a licence in Form 20-A shall be valid for only such drugs as are specified in the licence.
(2) A licence 3[to sell, stock, exhibit or offer for sale or distribute] drugs specified in Schedule C and C (1) excluding those specified in Schedule X, by retail on restricted licence or by wholesale shall be issued in Form 21, Form 21-A or Form 21-B, as the case may be.
4[Provided that a licence in Form 21-A shall not be granted for drugs specified in Schedule C and shall be valid for only such Schedule C (1) drugs as are specified in the licence.]
(3)A licence 3[to sell, stock, exhibit or offer for sale or distribute] drugs specified in Schedule X by retail or by wholesale shall be issued in Form 20-F or Form 20-G as the case may be.]
62. Sale at more than one place.__ If drugs are sold or stocked for sale at more than one place, separate application shall be made, and a separate licence shall be issued, in respect of each such place:
5Provided that this shall not apply to itinerant vendors who have no specified place of business and who will be licensed to conduct business in a particular area within the jurisdiction of the licensing authority
__________________________________________________________________ 1Amended by G.O.I. No. F. 1-16/57-D, dated 15th June, 1957 2Subs by G.O.I.Notification No. G.S.R 462(E) dated 22-6-1982 3Amended by G.O.I. Notification No. G.S.R 788(E) dated 10-10-1985 4Substituded by G.O.I.Notification No. G.S.R 487(E) dated 2-7-1984 5Added under Government of India Notification No. F. 10-21/49-D, dated 10th March, 1953
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162A. Restricted licences in Forms 20-A and 21-A. __ (a) Restricted licences in Forms 20-A and 21-A shall be issued subject to the discretion of the Licensing Authority, to dealers or persons in respect of drugs whose sale does not require the supervision of a qualified person.
(b)Licences to itinerant vendors shall be issued only in exceptional circumstances for bona fide traveling agents of firms dealing in drugs or for a vendor who purchases drugs from a licensed dealer for distribution in sparsely populated rural areas where other channels of distribution of drugs are not available.
(c)The licensing authority may issue a licence in Form 21-A to a travelling agent of a firm but to no other class of itinerant vendors for the specific purpose of distribution to medical practitioners or dealers, samples of biological and other special products specified in Schedule C:
Provided that traveling agents of licensed manufacturers, agents, of such manufacturers and importers of drugs shall be exempted from taking out licence for the free distribution of samples of medicines among members of the medical profession, hospitals, dispensaries and the medical institution or research institutions.
262-B.Conditions to be satisfied before a licence in Form 20-A or Form 21-A is granted. __ (1) A licence in Form 20-A or Form 21-A shall not be granted to any person, unless the authority empowered to grant the licence is satisfied that the premises in respect of which the licence is to be granted are adequate and equipped with proper storage accommodation for preserving the properties of drugs to which the licence applies:
Provided that this condition shall not apply in the case of licence granted itinerant vendors.
(2)In granting a licence under Rule 62-A the authority empowered to grant it shall have regard to :____
(i) the number of licences granted in the locality during one year immediately preceding; and
(ii) the occupation, trade or business carried on by such applicant : __________________________________________________________________
1Added under Government of India Notification No. F. 10-21/49-D, dated 10th March, 1953. 2 Added under Government of India Notification No. F. 1-9/60-D, dated 3rd July, 1961.
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Provided that the licensing authority may refuse to grant or renew a licence to any applicant or licensee in respect of whom it is satisfied that by reason of his conviction of an offence under the Act or these Rules or the previous cancellation or suspension of any licence granted thereunder, he is not a fit person to whom a licence should be granted under this Rule.
(3) Any person who is aggrieved by the order passed by the licensing authority in sub-rule (1) may, within 30 days from the date of the receipt of such order appeal to the State Government and the State Government may, after such enquiry into the matter as it considers necessary and after giving the appellant an opportunity for representing his views in the matter make such order in relation thereto as it thinks fit.
162C.Application for licence to sell drugs by wholesale or to distribute the same from a motor vehicle: ___
(1)Application for the grant or renewal of a licence to sell by wholesale or to distribute from a motor vehicle shall be made to the Licensing Authority in Form 19-AA and shall be accompanied by 2[a fee of rupees five hundred]:
Provided that if the applicant applies for the renewal of a licence after its expiry but within six months of such expiry , the fee payable for renewal of such licence shall be 2[rupees five hundred plus an additional fee at the rate of rupees two hundred and fifty per month or part thereof].
(2) A fee of 2[rupees one hundred fifty] shall be paid for a duplicate copy of a licence issued under this rule, if the original is defaced, damaged or lost.
162D.Form of licences to sell drugs by wholesale or distribute drugs from a motor vehicles.
A licence shall be issued for sale by wholesale or for distribution from a motor vehicle of drugs other than those specified in Schedule and Schedule C(1) in Form 20BB and of drugs specified in Schedule C and Schedule C(1) in Form 21BB :
Provided that such a licence shall not be required in a case where a public carrier or a hired vehicle is used for transportation or distribution of drug.
363.Duration of licence.__ An original licence or a renewed licence to sell drugs, unless sooner suspended or cancelled, shall be 2[valid for a period of five years on and from the date on which] it is granted or renewed :
__________________________________________________________________ 1Added by G.O.I. Notification No. X11013/7/76__DGHS dated the 25th January 1979.
2Amended by G.O.I. Notification No. G.S.R 601(E) dated 24-08-2001 3Amended by G.O.I. Notification No. F. 1-10/62-D, dated 10th April, 1964.
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1Provided that if the application for renewal of licence in force is made before its expiry or if the application is made within six months of its expiry, after payment of additional fee, the licence shall continue to be in force until orders are passed on the application. The licence shall be deemed to have expired if application for its renewal is not made within six months after its expiry.
263A.Certificate of renewal of a sale licence.__ The certificate of renewal of a sale licence in Forms 20, 20-A, 20-B,3[20-F, 20-G], 21, 21-A and 21-B shall be issued in Form 21-C.
463B. Certificate of renewal of licence.__ A certificate of renewal of a licence in Form 20BB or Form 21BB shall be issued in Form 21-CC.;
564.Conditions to be satisfied before a licence in Form3[20, 20-B, 20-F,20-G 21 or 21-B] is granted .__(1)A licence in Form 3[20, 20-B, 20-F,20-G, 21 or 21-B] 6[to sell, stock, exhibit or offer for sale or distribute]drugs shall not be 7[granted or renewed] to any person unless the authority empowered to grant the licence is satisfied that the premise in respect of which the licence is to be 7[granted or renewed] are adequate, equipped with proper storage accommodation for preserving the properties of the drugs to which the licence applies and are in charge of a person competent in the opinion of the licensing authority to supervise and control the sale, distribution and preservation of drugs :
Provided that in the case of a pharmacy a licence in Form 20 or 21 shall not be 7[granted or renewed] unless the licensing authority is satisfied that the requirements prescribed for a pharmacy in Schedule N have been complied with.
3[Provided further that licence in Form 20-F shall be 7[granted or renewed] only to a pharmacy and in areas where a pharmacy is not operating, such licence may be 7[granted or renewed] to a chemist and druggist]
Explanation.__ For the purpose of this rule the term ‘Pharmacy’ shall be held to mean to include every store or shop or other place : (1) where drugs are dispensed, that is, measured or weighed or mode up and supplied : or (2), where prescriptions are compounded; or (3) where drugs are prepared; or (4) which has upon it or displayed within it, or affixed to or used in connection with it, a sign bearing the word or words “Pharmacy”, “Pharmacist,” “Dispensing Chemist” or “Pharmaceutical Chemist”; or (5) which, by sign, symbol or indication within or. __________________________________________________________________
1Amended by S. O. No. 2139, dated 12th August, 1972 (Govt. of India Notification No. X. 11014/12/72-D, dated the 5th June, 1972). 2Added under Government of India Notification No. F. 1-10/62-D, dated 10th April, 1964.
3Inserted by Notification No. G.S.R 462(E) dated 22-6-1982 4Added by Govt. of India Notification No. X11013/7/76__DGHS dated the 25th January 1979. 5Amended by Government of India Notification No. F. 1-16/57-D, dated 15th June 1957 and No. F. 1-19/59- D, dated 13th June, 1961 6Amended by G.O.I. Notification No. G.S.R 778(E) dated 10-10-1985 7Amended by G.O.I. Notification No. G.S.R 681(E) dated 6-6-1988
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upon it gives the impression that the operations mentioned at (1), (2) and (3) are carried out in the premises; or (6) which is advertised in terms referred to in (4) above
(2)In granting a licence under sub-rule (1) the authority empowered to grant it shall have regard____
1(i)to the average number of licences granted during the period of 3 years immediately preceding, and
(ii)to the occupation, trade or business ordinarily carried on by such applicant during the period aforesaid :
Provided that the licensing authority may refuse to grant or renew a licence to any applicant or licensee in respect of whom it is satisfied that by reason of his conviction of an offence under the Act or these Rules, or the previous cancellation or suspension of any licence granted thereunder, he is not a fit person to whom a licence should be granted under this rule. Every such order shall be communicated to the licensee as soon as possible.
2[ Provided further that in respect of an application for the grant of a licence in form 20-B or form 21-B or both, the licensing authority shall satisfy himself that the premises in respect of which a wholesale licence is to be granted are:--
(i) of an area of not less than ten square meters; and]
3[(ii) in the charge of a competent person, who— (a) is a Registered Pharmacist, or, (b) has passed the matriculation examination or its equivalent examination from a
recognised Board with the four years experience in dealing with sale of drugs, or; (c) holds a degree of a recognised University with one year’s experience in dealing
with drugs] 4[Provided also that,--
(i) in respect of an application for the grant of a licence in Form 20 or Form 21 or both, the licensing authority shall satisfy itself that 5[the premises are of an area] of not less than 10 square meters, and
(ii) in respect of an application for the grant of a licence-- (A)In Form 20 or Form 21 or both, and (B)In Form 20 B or Form 21B or both,
the licensing authority shall satisfy itself that the premises are of an area not less than 15 square meter;
__________________________________________________________ 1Amended by Government of India Notification No. F. 1-19/59-D, dated 13th June, 1961 2 Ins. by G.O.I. Notification No. G.S.R 681(E) dated 5-12-1980 3Amended by G.O.I. Notification No. G.S.R 351(E) dated 26-4-2000 4 Ins. by G.O.I.Notification No. G.S.R 91(E) dated 25-2-1997 5Amended by Corrigendum G.S.R. 121 (E) dated 5-3-1998
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Provided also that the provisions of the preceding proviso shall not apply to the premises for which licences have been issued by the licensing authority before the commencement of the Drugs and Cosmetic (1st Amendment) Rules, 1997]
6[(3) Any person who is aggrieved by the order passed by the licensing authority in sub-rule (1) may, within 30 days from the date of receipt of such order, appeal to the State Government and the State Government may, after such enquiry into the matter as it considers necessary and after giving the appellant an opportunity for representing his views in the matter, make such an order in relation thereto as it thinks fit.]
65. Condition of licences. __ Licences in 1[Form 20, 20-A, 20-B, 20-F, 20-C, 21, and 21-B] shall be subject to the conditions stated therein and to the following general conditions___
1[(1) Any drug shall, if compounded or made on the licensee’s premises be compounded or made under the direct and personal supervision of a 2[registered Pharmacist]
(2)The supply, otherwise than by way of wholesale dealing, 3[* * *] of any drug supplied on the prescription of a Registered Medical Practitioner shall be effected only by or under the personal supervision of a 2[registered Pharmacist].
4(3) (1) The supply of any drug 1[other than those specified in Schedule X] on a prescription of a Registered Medical Practitioner shall be recorded at the time of supply in a prescription register specially maintained for the purpose and the serial number of the entry in the register shall be entered on the prescription. The following particulars shall be entered in the register: _
(a) serial number of the entry,
(b) the date of supply,
(c) the name and address of the prescriber, 5(d) the name and address of the patient, or the name and address of the owner of
the animal if the drug supplied is for veterinary use. (e) the name of the drug or preparation and the quantity or in the case of a
medicine made up by the licensee, the ingredients and quantities thereof, (f) in the case of a drug specified in 1[Schedule C or Schedule H] the name of the
manufacturer of the drug, its batch number and the date of expiry of potency, if any,
(g) the signature of the 2[registered Pharmacist] by or under whose supervision the medicine was made up or supplied.
________________________________________________________________ 1Subs. by G.O.I. Notification No. G.S.R 462(E) dated 22-6-1982 2Subs. by G.O.I.Notification No. G.S.R 676(E) dated 06-09-1994 3Omitted by G.O.I.Notification No. G.S.R 462(E) dated 22-6-1982 4Amended by S. O. No. 2139, dated 12-8-1972 (Govt. of India Notification No. X. 11014/12/72-D, dated the 5th June, 1972.) 5Amended by GSR No. 926 dated 16-7-1977, (Govt. of India Notification No. X. 11014/6/76-D & M.S. dated 24-6-77). 6Amended by G.O.I. Notification No. F.1-9/60-D dated 3rd July,1961.
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Provided that in the case of drugs which are not compounded in the premises and which are supplied from or in the original containers, the particulars specified in items (a) to (g) above may be entered in a cash or credit memo book, serially numbered and specially maintained for this purpose:
Provided further that if the medicine is supplied on a prescription on which the medicine has been supplied on a previous occasion and entries made in the prescription register, it shall be sufficient if the new entry in the register includes a serial number, the date of supply, the quantity supplied and a sufficient reference to an entry in the register recording the dispensing of the medicine on the previous occasion.
Provided further that it shall not be necessary to record the above details in the register or in the cash or credit memo particulars in respect of: ___
(i) any drugs supplied against prescription under the Employees State Insurance Scheme if all the above particulars are given in that prescription, and
(ii) any drug other than that specified in 1[Schedule C or Schedule H] if it is supplied in the original unopened container of the manufacturer and if the prescription is duly stamped at the time of supply with the name of the supplier and the date on which the supply was made and on condition that the provisions of sub rule (4) (3) of this rule are complied with.
(2) The option to maintain a prescription register or a cash or credit memo book in respect of drugs and medicines which are supplied from or in the original container, shall be made in writing to the Licensing Authority at the time of application for the grant or renewal of the licence to sell by retail.
Provided that the Licensing Authority may require records to be maintained only in prescription register if it is satisfied that the entries in the carbon copy of the cash or credit memo book are not legible.
2(4) (1) The supply by retail, otherwise than on a prescription of a drug specified in Schedule C 3[* * *] shall be recorded at the time of supply either :
_________________________________________________________________ 1Subs. by G.O.I.Notification No. G.S.R 462(E) dated 22-6-1982 2Ins. by Government of India Notification No. 1-63/61-D, dated 17th July, 1963. 3Omitted by Notification No. G.S.R 462(E) dated 22-6-1982
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(i) in a register specially maintained for the purpose in which the following particulars shall be entered :____
(a) serial number of the entry, (b) the date of supply, (c) the name and address of the purchaser, (d) the name of the drug and the quantity thereof, (e) in the case of a drug specified in Schedule C, the name of the manufacturer, the
batch number and the date of expiry of potency, (f) the signature of the person under whose supervision the sale was effected, or
(ii) in a cash or credit memo book, serially numbered containing all the particulars specified in items (b) to (f) of sub clause (i) above.
NOTE:__ The entries in the carbon copy of the cash or credit memo which is retained by the licensee shall be maintained in a legible manner.
(2) The option to maintain a register or a cash or credit memo book shall be made in writing to the Licensing Authority at the time of application for the grant or renewal of a licence to sell by retail:
Provided that the Licensing Authority may require records to be maintained in a register if it is satisfied that the entries in the carbon copy of the cash/credit memo book are not legible.
(3)(i) The supply by retail of any drug shall be made against a cash/credit memo which shall contain the following particulars :____
(a) Name, address and sale licence number of the dealer, 1(b) Serial number of the cash/credit memo, (c) the name and quantity of the drug supplied.
(ii)Carbon copies of cash/credit memos shall be maintained by the licensee as record.
__________________________________________________________________ 1Ins. by G. S. R. No. 245 dated 21-2-1976 (Govt. of India Notification No X. 11013/5/72-D&M.S. dated the 3rd, February, 1976).
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1[(4)(i) Records of purchase of a drug intended for sale or sold by retail shall be maintained by the licensee and such records shall show the following particulars, namely:--
(a) the date of purchase,
(b)the name and address of the person from whom purchased and the number of the relevant licence held by him,
(c) the name of the drug, the quantity and the batch number, and
(d) the name of the manufacturer of the drug.
(ii) Purchase bills including cash or credit memo shall be serially numbered by the licensee and maintained by him in a chronological order,]
2(5)(1) Subject to the other provisions of these rules the supply of a drug by wholesale shall be made against a cash or credit memo bearing the name and address of the licensee and his licence number under the Drugs and Cosmetics Act in which the following particulars shall be entered____
(a) the date of sale.
(b) the name, address of the licensee to whom sold and his sale licence number. In case of sale to an authority purchasing on behalf of Government, or to a hospital, medical, educational or research institution or to a Registered Medical Practitioner for the purpose of supply to his patients the name and address of the authority, institution or the Registered Medical Practitioner as the case may be,
(c) the name of the drug, the quantity and the batch number,
(d) the name of the manufacturer.
3[(e) the signature of the competent person under whose supervision the sale was effected.]
(2)Carbon copies of cash or credit memos specified in clause (1) shall be preserved as records for a period of three years from the date of the sale of the drug.
__________________________________________________________________ 1Ins. by G.O.I.Notification No. G.S.R 1242(E) dated 17-9-1979 2Amended by G.O.I. No. F. 1-63/62-D, dated 17th July, 1963. 3Ins. by G.O.I. Notification No. G.S.R 496(E) dated 9-6-1995
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1[(3) (i) Records of purchase of a drug intended for resale or sold by wholesale shall be maintained by the licensee and such records shall show the following particulars, namely:--
(a) the date of purchase, (b) the name, address and the number of the relevant licence held by the person from
whom purchased, (c) the name of the drug, the quantity and the batch number, and (d) the name of the manufacturer of the drug.
(ii) Purchase bills including cash or credit memos shall be serially numbered by the licensee and maintained by him in a chronological order.]
(6) The licensee shall produce for inspection by an Inspector appointed under the Act on demand all registers and records maintained under these Rules, and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and Rules thereunder have been observed.
(7) Except where otherwise provided in these Rules, all registers and records maintained under these Rules shall be preserved for a period of not less than two years from the date of the last entry therein.
(8)Notwithstanding anything contained in this Rule it shall not be necessary to record particulars in a register specially maintained for the purpose if the particulars are recorded in any other register specially maintained under any other law for the time being in force.
2[(9) (a) Substances specified in Schedule H or Schedule X shall not be sold by retail except on and in accordance with the prescription of a Registered Medical Practitioner and in the case of substances specified in schedule X, the prescriptions shall be in duplicate,one copy of which shall be retained by the licensee for a period of two years.
(b)The supply of drugs specified in Schedule H or Schedule X to Registered Medical Practitioners, Hospitals, Dispensaries and Nursing Homes shall be made only against the signed order in writing which shall be preserved by the licensee for a period of two years;]
_________________________________________________________________ 1Subs. by G.O.I.Notification No. G.S.R 1242(E) dated 17-9-1979 2Ins. by G.O.I. Notification No. G.S.R 462(E) dated 22-6-1982
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(10) For the purposes of clause (9) a prescription shall____
(a) be in writing and be signed by the person giving it with his usual signature and be dated by him;
1(b) specify the name and address of the person for whose treatment it is given, or the name and address of the owner of the animal if the drug is meant for veterinary use;
(c) indicate the total amount of the medicine to be supplied and the dose to be taken.
(11) The person dispensing a prescription containing a drug specified in Schedule H 2[and Schedule X] shall comply with the following requirements in addition to other requirements of these Rules____
(a) the prescription must not be dispensed more than once unless the prescriber has stated thereon that it may be dispensed more than once;
(b) if the prescription contains a direction that it may be dispensed a stated number of times or at stated intervals it must not be dispensed otherwise than in accordance with the directions;
(c) at the time of dispensing there must be noted on the prescription above the signature of the prescriber the name and address of the seller and the date on which the prescription is dispensed.
3(11-A) No person dispensing a prescription containing substances specified in 2[Schedule H or X], may supply any other preparation, whether containing the same substance or not, in lieu thereof.
2[(12) Substances specified in Schedule X kept in retail shop or premises used in connection therewith shall be stored—
(a) under lock and key in cupboard or drawer reserved solely for the storage of these substances ;or
(b) in a part of the premises separated from the remainder of the premises and to which only responsible persons have access;]
__________________________________________________________________ 1Amended by G. S. R. No. 926, dated 16-7-1977 (Govt. of India Notification No. X. 11014/6/76-D & M. S. dated 24/6/1977).
2Ins./amended/subs by Notification No. G.S.R 462(E) dated 22-6-1982 3Amended by G. S. R. No. 926, dated 16-7-1977 (Govt. of India Notification No. X. 11014/6/76-D & M. S. dated 24/6/1977).
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(13) 1 * * * (14) 1 * * *
2(15) (a) The description “Drugstore” shall be displayed by such licensees who do not require the services of a qualified person.
(b) The description “Chemists and Druggists” shall be displayed by such licensees who employ the services of a “3[registered Pharmacist]” but who do not maintain a “Pharmacy” for compounding against prescriptions:
(c) The description “Pharmacy”, “Pharmacist”, “Dispensing Chemist” or “Pharmaceutical Chemist” shall be displayed by such licensees who employ the services of a “3[registered Pharmacist]” and maintain a “Pharmacy” for compounding against prescriptions:
4[Explanation:-- for the purpose of this rule,---
(i) “registered Pharmacist” means a person who is a registered Pharmacist as defined in clause (i) of Section (2) of the Pharmacy Act, 1948 (Act No. 8 of 1948).
Provided that the provisions of sub-clause (i) shall not apply to those persons who are already approved as “qualified person” by the Licensing authority on or before 31st December 1969.
(ii) Date of Expiry of potency means the date that is recorded on the container, label or wrapper as the date up to which the substance may be expected to retain potency not less than or not to acquire toxicity greater than that required or permitted by the prescribed test.
5(16) The license shall maintain an Inspection Book in Form 35 to enable an Inspector to record his impressions and the defects noticed.
__________________________________________________________________ 1Omitted by Notification No. G.S.R 462(E) dated 22-6-1982 2Amended by the Government of India Notification No. F. 1-16/57-D, dated 15th June, 1957. 3Substituted by Notification No. G.S.R 676(E) dated 06-09-1994 4Subs. by Notification No. G.S.R 676(E) dated 06-09-1994 5Amended by Government of India Notification No. F. 1-14/68-D dated 26-10-1968.
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1(17) No drug shall be sold or stocked by the licensee after the date of expiration of potency recorded on its container, label or wrapper, or in violation of any statement or direction recorded on such container, label or wrapper;
Provided that any such drugs in respect of which the licensee has taken steps with the manufacturer or his representative for the withdrawal, reimbursement or disposal of the same, may be stocked after the date of expiration of potency pending such withdrawal, reimbursement or disposal, as the case may be, subject to the condition that the same shall be stored separately from the trade stocks 2and all such drugs shall be kept in packages or cartons, the top of which shall display prominently, the words “Not for sale”.
3(18) No drug intended for distribution to the medical profession as free sample which bears a label on the container as specified in clause (viii) of sub-rule (1) of rule 96, and no drug meant for consumption by the Employees’ State Insurance Corporation, the Central Government Health Scheme, the Government Medical Stores Depots, the Armed Forces Medical Stores or other Government institutions, which bears a distinguishing mark or any inscription on the drug or on the label affixed to the container thereof indicating this purpose shall be sold or stocked by the licensee on his premises.
4[ Provided that this sub- rule shall not be applicable to licensees who have been appointed as approved chemists, by the State Government in writing, under the employees’ State Insurance Scheme, or have been appointed as authorized agent or distributor, by the manufacturer in writing, for drugs meant for consumption under the Central Government Health Scheme, the Government Medical Stores Depots, the Armed Forces Medical Stores or other Government Institutions for drugs meant for consumption under those schemes 5[or have been appointed as authorized Depots or Carrying and Forwarding agent by the manufacturer in writing, for storing free samples meant for distribution to medical profession.] subject to the conditions that the stock shall be stored separately from the trade stocks and shall maintain separate records of the stocks received and distributed by them.]
__________________________________________________________________ 1Added under Government of India Notification No. F. 1-55/61-D, dated 22nd August, 1964. 2Added by S. O. No. 903, dated 28-2-1976 (Govt. of India Notification No. X. 11013/2/75-D & MS. Dated 10-2-1976). 3Added under Government of India, Ministry of Health, F. P., W. H. and U. D. Notification No. 1-113/69- D, dated 23-12-69. 4Substituted by Notification No. G.S.R 496(E) dated 09-06-1995
5Inserted by G.O.I. Notification No. G.S.R 352(E) dated 26-04-2000
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1(19) The supply by retail of any drug in a container other than the one in which the manufacturer has marketed the drug, shall be made only by dealers who employ the services of a “2[registered Pharmacist]” and such supply shall be made under the direct supervision of the “2[registered Pharmacist]” in an envelope or other suitable wrapper or container showing the following particulars on the label :
(a) name of the drug, (b) the quantity supplied, (c) the name and address of the dealer.
3(20) The medicines for treatment of animals kept in a retail shop or premises shall be labeled with the words ‘Not for human use__ for treatment of animals only’ and shall be stored____
(a) in a cupboard or drawer reserved solely for the storage of veterinary drugs, or
(b) in a part of the premises separated from the remainder of the premises to which customers are not permitted to have access.
4[(21) (a) The supply of drugs specified in Schedule X shall be recorded at the time of supply in a register (bound and serially page numbered) specially maintained for the purpose and separate pages shall be allotted for each drug.
(b) The following particulars shall be entered in the said register, namely:-- (i) Date of transaction; (ii) Quantity received, if any, the name and address of the supplier and the
number of the relevant licence held by the supplier; (iii) Name of the drug; (iv) Quantity supplied; (v) Manufacturer’s name; (vi) Batch No. or Lot No; (vii) Name and address of the patient purchaser; (viii) Reference Number of the prescription against which supplies were made. (ix) Bill No and date in respect of purchases and supplies made by him; (x) Signature of the person under whose supervision the drugs have been
supplied.] __________________________________________________________________
1Added by G. S. R. No. 444 dated 28-4-1973 [Govt. of India Notification No. X. 11014/4/72-D (Pt.) dated the 31st March, 1973]. 2Substituted by G.O.I.Notification No. G.S.R 676(E) dated 06-09-1994 3Added by G. S. R. No. 926 dated 16-7-1977 (Govt. of India Notification No. X. 11014/6/76-D & MS. Dated 24-6-1977). 4Added by G.O.I. Notification No. G.S.R 462(E) dated 22-6-1982
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66. Cancellation and suspension of licences. __ (1) The Licensing Authority may, after giving the licensee an opportunity to show cause why such an order should not be passed by an order in writing stating the reasons therefor, cancel a licence issued under this Part or suspend it for such period as he thinks fit, either wholly or in respect of some of the substances to which it relates, if in his opinion, the licensee has failed to comply with any of the conditions of the licence or with any provisions of the Act or Rules thereunder:
1Provided that, where such failure or contravention is the consequence of an act or omission on the part of an agent or employee, the licence shall not be cancelled or suspended if the licensee proves to the satisfaction of the licensing authority:___
(a) that the act or omission was not instigated or connived at by him or, if the licensee is a firm or company by a partner of the firm or a director of the company, or
(b) that he or his agent or employee had not been guilty of any similar act or omission within twelve months before the date on which the act or omission in question took place, or where his agent or employee had been guilty of any such act or omission the licensee had not or could not reasonably have had, knowledge of that previous act or omission, or
(c) if the act or omission was a continuing act or omission, he had not or could not reasonable have had knowledge of that previous act or omission, or
(d) that he had used due diligence to ensure that the conditions of the licence or the provisions of the Act or the Rules thereunder were observed.
2(2)A licensee whose licence has been suspended or cancelled may, within three months of the date of order under sub-rule (1), prefer an appeal against that order to the State Government, which shall decided the same.
3[66A. Procedure for disposal of drugs in the event of cancellation of licence.—(1) In case a licensee, whose licence has been cancelled, desires to dispose of drugs he has in his possession in the premises in respect of which the licence has been cancelled, he shall apply in writing to the licensing authority for this purpose, giving the following particulars, namely:—
(a)the name and address of the person to whom the drugs are proposed to be sold or supplied together with the number of the licence for sale or manufacture as the case may be held by him.
_________________________________________________________________ 1Added by S. O. No. 2139, dated 12-8-1972 (Govt. of India Notification No. 9-817DGHS/77 2Amended by G. S. R. No. 926 dated 16-7-1977 (Govt. of India Notification No. X. 11014/6/76-D& M.S. dated 24-6-1977). 3Inserted by G.O.I. Notification No. G.S.R 1242(E) dated 17-9-1979
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(b) the names of drugs together with their quantities, batch numbers, the names and addresses of their manufacturers and the dates of their expiry, if any, proposed to be sold to the person mentioned in clause (a).
(2) The licensing authority may, after examination of the particulars referred to in sub- rule (1) and, if necessary, after inspection by an Inspector of the premises where the drugs are stocked, grant the necessary permission for their disposal.]
PART VI-A – SALE OF HOMEOPATHIC MEDICINES 167-A. (1) The State Government shall appoint Licensing Authorities for the purpose of this
Part for such areas as may be specified.
(2) Application for the grant or renewal of a licence 2[to sell, stock or exhibit or offer for sale or distribute] Homoeopathic medicines shall be made in Form 19-B to the Licensing Authority and shall be accompanied by a 3[fee of rupees two hundred and fifty];
4Provided that if the applicant applies for renewal of licence after its expiry but within six months of such expiry the fee payable for renewal of such licence shall be 3[rupees two hundred and fifty plus an additional fee at the rate of rupees fifty or part thereof].
5(3) If the original licence is either defaced, damaged or lost, a duplicate copy thereof may be issued on payment of a 3[fee of rupees fifty.]
67-B. A Licensing Authority may, with the approval of the State Government, by an order in writing, delegate the power to sign licences and such other powers, as may be specified, to any other person under his control.
67-C. Forms of licences to sell drugs.__ (1) A licence 2[to sell, stock or exhibit or offer for sale or distribute] Homoeopathic medicines by retail or by wholesale shall be issued in Form 20- C or 20-D as the case may be.
__________________________________________________________________ 1Added under Government of India Notification No. F. 1-35/64-D, dated 18th August, 1964. 2Amended by G.O.I. Notification No. G.S.R 788(E) dated 10-10-1985 3Amended by G.O.I. Notification No. G.S.R 601(E) dated 24-8-2001 4Amended by S. O. No. 2139 dated 12-8-1972 (Govt. of India Notification No. X. 11014/12/72-D dated the 5th June, 1972). 5Added by G. S. R. No. 665, dated 28-5-77 (Govt. of India Notification No. X. 11014/2/77-D & M. S., dated 6-5-1977).
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67-D. Sale at more than one place.__ If drugs are sold or stocked for sale at more than one place, a separate application shall be made and a separate licence shall be obtained in respect of each place.
67-E. Duration of licences.__ An original licence or a renewed licence unless it is sooner suspended or cancelled shall be 1[valid for a period of five years on and from the date on which] it is granted or renewed :
2Provided that if the application for renewal of a licence in force is made before its expiry or if the application is made within six month of its expiry, after payment of additional fee, the licence shall continue to be in force until orders are passed on the application and the licence shall be deemed to have expired if application for its renewal is not made within six months after its expiry.
367-EE. Certificate of renewal.__ The certificate of renewal of a sale licence in Forms 20-C and 20-D shall be issued in Form 20-E.
67-F. Condition to be satisfied before a licence in Form 20-C or Form 20-D is granted.
(1) A licence in Form 20-C or Form 20-D to 4[to sell, stock or exhibit or offer for sale or distribute] Homoeopathic medicines shall not be granted to any person unless the authority empowered to grant the licence is satisfied that the premises in respect of which the licence is to be granted are clean and in the case of a licence in Form 20-C the sale premises is in charge of a person who is or has been dealing in Homoeopathic medicines and who is in the opinion of the Licensing Authority competent to deal in Homoeopathic medicines.
5[Provided that no registered Homeopathic medical practitioner who is practicing Homeopathy in the premises where Homeopathic medicines are sold shall deal in Homeopathic medicines;]
(2) Any person who is aggrieved by the order passed by the Licensing Authority under sub- rule (1) may within 30 days from the date the receipt of such order appeal to the State Government and the State Government may, after such enquiry into the matter as it considers necessary and after giving the appellant an opportunity for representing his case, make such order in relation thereto as it thinks fit. __________________________________________________________________
1Amended by G.O.I. Notification No. G.S.R 601(E) dated 24-8-2001 2Amended by S. O. No. 2139 dated 12-8-1972 (Govt. of India Notification No. X. 11014/12/72-D dated the 5th June, 1972). 3Added under Government of India, Ministry of Health, F. P., W. H. and U. D. Notification No. F. 1-14/67-D, dated the 3rd February, 1969.
4Amended by G.O.I. Notification No. G.S.R 788(E) dated 10-10-1985 5Ins. by Notification No. G.S.R 680(E) dated 5-12-1980
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67-G. Conditions of licence.__ Licence in Form 20-C or 20-D shall be subject to the conditions stated therein and to the following further conditions, namely:___
(1) The premises where the Homoeopathic medicines are stocked for sale or sold are maintained in a clean condition.
(2) The sale of Homoeopathic medicines shall be conducted under the supervision of a person, competent to deal in Homoeopathic medicines.
(3) The licensee shall permit an Inspector to inspect the premises and furnish such information as he may require for ascertaining whether the provisions of the Act and the Rules made thereunder have been observed.
(4) The licensee in Form 20-D shall maintain records of purchase and sale of Homoeopathic medicines containing alcohol together with names and addresses of parties to whom sold.
1(5) The licensee in Form 20-C shall maintain records of purchase and sale of Homoeopathic medicines containing alcohol. No records of sale in respect of Homoeopathic potentised preparation in containers of 30 ml. or lower capacity and in respect of mother tinctures made up in quantities upto 60 ml. need be maintained.
2[(6) The licensee shall maintain an Inspection Book in Form 35 to enable an Inspector to record his impressions and the defects noticed.]
367-GG. Additional information to be furnished by an applicant for licence or a licensee to the Licensing Authority :____
The applicant for the grant of a licence or any person granted a licence under this Part shall, on demand furnish to the Licensing Authority, before the grant of the licence or during the period the licence is in force as the case may be, documentary evidence in respect of the ownership or occupation or rental or other basis of the premises, specified in the application for licence or in the licence granted, constitution of the firm, or any other relevant matter, which may be required for the purpose of verifying the correctness of the statements made by the applicant or the licensee, while applying for or after obtaining the licence, as the case may be.
__________________________________________________________________ 1Added under Government of India, Ministry of Health, F. P. , W. H. and U. D. Notification No. F. 1-59/68- D, dated the 19th November, 1969. 2Ins. by G.O.I. Notification No. G.S.R 351(E) dated 8-5-1984 3Added by S. O. No. 2139 dated 12-8-1972 (Govt. of India Notification No. X. 11014/12/72-D dated the 5th June, 1972).
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67-H.Cancellation and suspension of licences____
(1)The Licensing Authority may, after giving the licensee an opportunity to show cause why such an order should not be passed by an order in writing stating the reasons therefor, cancel a licence issued under this Part or suspend it for such period as he thinks fit, if in his opinion, the licensee has failed to comply with any of the conditions of the licence or with any provisions of the Act or Rules made thereunder :
1Provided that, where such failure or contravention is the consequence of an act or omission on the part of an agent or employees, the licence shall not be cancelled or suspended if the licensee proves to the satisfaction of the Licensing Authority :___
(a) that the act or omission was not instigated or connived at by him or, if the licensee is a firm or company, by a partner of the firm or a director of the company, or
(b) that he or his agent or employee had not been guilty of any similar act or omission within twelve months before the date on which the act or omission in question took place, or where his agent or employee had been guilty of any such act or omission, the licensee had not or could not reasonably have had, knowledge of that previous act or omission, or
(c) if the act or omission was a continuing act or omission that he had not or could not reasonably have had knowledge of that previous act or omission, or
(d) that he had used due diligence to ensure that the conditions of the licence or the provisions of the Act or the Rules thereunder were observed.
2(2) A licensee whose licence has been suspended or cancelled may, within three months of the date of the order under sub-rule (1), prefer an appeal against that order to the State Government, which shall decide the same.
__________________________________________________________________ 1Added by S. O. No. 2139 dated 12-8-1972 (Govt. of India Notification No. X. 11014/12/72-D dated the 5th June, 1972). 2Amended by G.S.R. No. 926 dated 16/7/1977 (Govt. of India Notification No. X. 11014/6/76-D & M. S. dated 24-6-1977)
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PART VII ___ 1[MANUFACTURE FOR SALE OR FOR DISTRIBUTION] OF DRUGS OTHER THAN HOMOEOPATIC MEDICINES
68. Manufacture on more than one set of premises. __ If drugs are manufactured on more than one set of premises a separate application shall be made and a separate licence shall be issued in respect of each such set of premises.
2[68-A Grant or Renewal of Licences by the Central Licence Approving Authority.— (1) Notwithstanding anything contained in this part, on and from the commencement of the Drugs and Cosmetics( Ninth Amendment) Rules.1992, a licence for the manufacture for sale or distribution of drugs as specified from time to time by the Central Government by notification in the Official Gazette, for the purpose of this rule, shall be granted or renewed, as the case maybe, by the Central Licence Approving Authority (appointed by the Central Government.)
Provided that the application for the grant or renewal of such licence shall be made to the licensing Authority.
(2) On receipt of the application for grant or renewal of a licence, the licensing authority shall,--
(i) verify the statement made in the application Form; (ii) cause the manufacturing and testing establishment to be inspected in accordance
with the provisions of rule 79; and (iii) in case the application is for the renewal of licence, call(s) for the informations of
the past performance of the licensee.
(3) If the licensing authority is satisfied that the applicant is in a position to fulfill the requirements laid down as in these rules, he shall prepare a report to that effect and forward it 3[along with the application and the licence (in triplicate) to be granted and renewed , duly completed] to the Central Licence Approving Authority :
Provided that if the licensing authority is of the opinion that the applicant is not in a position to fulfil the requirements laid down in these rules, he may, by order, for reasons to be recorded in writing, refuse to grant or renew the licence as the case may be.
(4) If on receipt of the application and the report of the licensing authority referred to in sub- rule (3) and after taking such measures including inspection of the premises by the Inspector, appointed by the Central Government under section 21 of the Act, with or without
__________________________________________________________________ 1Amended by G.O.I. Notification No. G.S.R 788(E) dated 10-10-1985 2Ins. by Notification No. G.S.R 923(E) dated 14-12-1992 3Amended by Notification No. G.S.R 89(E) dated 14-2-1996
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an expert in the concerned field if deemed necessary, the Central Licence Approving Authority, is satisfied that the applicant is in a position to fulfill the requirements laid down in these rules, he may grant or renew the licence, as the case may be:
Provided that if the Central Licence Approving Authority is of the opinion that the applicant is not in a position to fulfill the requirements laid down in these rules, he may, not withstanding the report of the licensing authority, by order, for reasons to be recorded in writing, reject the application for grant or renewal of licence as the case may be.
68-B. Delegation of Powers by the Central Licence Approving Authority.—The Central Licence Approving Authority may with the approval of the Central Government, by notification delegate his powers of signing licences and any other powers under the rules to any person under his control having same qualifications as prescribed for controlling authority under rule 50A for such areas and for such periods as may be specified. ]
169. Application for licence to manufacture drugs other than those specified in Schedules C and C(1) to the Drugs and Cosmetics Rules.___
2[(1) Application for grant or renewal of 4[licence to manufacture for sale or for distribution]of drugs, other than those specified in Schedule C and C (1) shall be made to the licensing authority appointed by the State Government for the purpose of this part (hereinafter in this part referred to as the licensing authority) and shall be made--
(a) in the case of repacking of drugs excluding those specified in Schedule X for sale or distribution in Form24-B;
(b) in the case of manufacture of drugs included in Schedule X in Form24-F;
(c) in any other case, in Form 24.]
3[( 2)(a) Every application in Form24-B shall be made up to ten items for each category of drugs categorized in Schedule M and shall be accompanied by a licence fee of rupees five hundred plus and an inspection fee of rupees two hundred for every inspection or for the purpose of renewal of the licence.
__________________________________________________________________ 1Amended by Government of India Notification No. F. 1-22/59-D, dated 9th April, 1960. 2Amended by G.O.I. Notification No. G.S.R 462(E) dated 22-06-1982 3Amended by G.O.I.Notification No. G.S.R 601(E) dated 24-8-2001 4 Subs.by G.O.I.Notification No.G.S.R.788(E) dt 10.10.1995.
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(b) Every application in Form 24F shall be made up to ten items for each category of drugs categorized in Schedule M and shall be accompanied by a licence fee of rupees six thousand and an inspection fee of rupees one thousand and five hundred for every subsequent inspection or for the purpose of renewal of licence.
(c) Every application in Form 24 shall be made up to ten items for each category of drugs catogarised in Schedule M and Schedule M-III and shall be accompanied by a licence fee of rupees six thousand and an inspection fee of one thousand and five hundred for every inspection or for the purpose of renewal of the licence;]
1[(3) If a person applies for the renewal of a licence after the expiry thereof but within six months of such expiry the fee payable for the renewal of such licence shall be:--]
2[(i) in the case of Form 24-B a licence fee of rupees five hundred plus an additional fee at the rate of rupees two hundred and fifty per month or part thereof in addition to an inspection fee of rupees two hundred;
(ii) in the case of Form 24-F a licence fee of rupees six thousand plus an additional fee at the rate of rupees one thousand per month or part thereof in addition to an inspection fee of rupees one thousand;
(iii) in the case of Form 24 a licence fee of rupees six thousand plus an additional fee at the rate of rupees one thousand per month or part thereof in addition to an inspection fee of rupees one thousand and five hundred;]
1[(4) A fee 2[rupees one thousand shall be paid] for a duplicate copy of the licence issued under clause (a), clause (b) or clause (c) of sub-rule (1) if the original is defaced, damaged or lost.]
2[(5) Applications by licensees to manufacture additional items of drugs shall, in the case of a licence to manufacture for sale and distribution for repacking and other than those specified in Schedule C and Schedule C (1), be made to the licensing Authority. Such applications shall, if the additional items of drugs applied for belong to categories which are not already included in the licence, be accompanied by an additional fee at the rate of rupees one hundred for each additional items of drug for repacking and rupees three hundred per additional item of drugs categorized in Schedule M and Schedule M-111.]
__________________________________________________________________ 1Amended by Notification No. G.S.R 462(E) dated 22-06-1982 2 Subs by Notification No. G.S.R 601(E) dated 24-8-2001
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1[(6) Where an application under this rule is for the manufacture of drug formulations falling under the purview of new drug as defined in rule 122-E, such application shall also be accompanied with approval, in writing in favour of the applicant, from the licensing authority as defined in clause (b) of rule21.]
Explanation.___ For the purpose of these rules, the term ‘repacking’ means the process of breaking up any drug from a bulk container into small package and the labeling of each such package with a view to its sale and distribution, but does not include the compounding or dispensing or the packing of any drug in the ordinary course of the retail business.
269-A. Loan Licences. 3[(1) Application for the grant or renewal of loan licences to manufacture for sale or for distribution of drugs other than those specified in Schedule C, Schedule C (1) and Schedule X shall be made up to ten items for each category of drugs categorised in Schedule M and Schedule M-111 and shall be made in Form 24-A accompanied by a licence fee of rupees six thousand and an inspection fee of rupees one thousand and five hundred to the licensing authority:
Provided that if the applicant applies for the renewal of a licence after, its expiry but within six months of such expiry, the fee payable for renewal of such licence shall be accompanied by a licence fee of rupees six thousand and an inspection fee of rupees one thousand and five hundred plus an additional fee at the rate of rupees one thousand per month or part thereof.]
Explanation. ___ For the purpose of this rule a loan licence means a licence which a licensing authority may issue to an applicant who does not have his own arrangements for manufacture but who intends to avail himself of the manufacturing facilities owned by a licensee in Form 25.
(2) The Licensing Authority shall, before the grant of a loan licence, satisfy himself that the manufacturing unit has adequate equipment, staff, capacity for manufacture, and facilities for testing, to undertake the manufacture on behalf of the applicant for a loan licence.
3[(3) subject to the provisions of sub-rule (2), application for manufacture of more than ten items for each category of drug on a loan licence shall be accompanied by an addition fee of rupees three hundred per additional item specified in Schedule M and Schedule M-111]
_________________________________________________________________ 1Ins. by G.O.I.Notification No. G.S.R 311(E) dated 1-5-2002 2Amended by the Government of India Notification No. F. 1-16/57-D, dated 15th June, 1957. 3Subs by G.O.I. by Notification No. G.S.R 601(E) dated 24-8-2001
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1(4)If the Licensing Authority is satisfied that a loan licence is defaced, damaged or lost or otherwise rendered useless, he may, on payment of a 2[fee of rupees one thousand] issue a duplicate licence.
69-B. [ * * *] Omitted as per G.O.I. Notification No. GSR 944(E) dt 21.9.1988.
3[70. Form of licence to repack or manufacture drugs other than those specified in Schedules C and C(1).- Licences for repacking of drugs against application in Form 24-B shall be granted in Form 25-B, licences for manufacture of drugs included in Schedule X and against application in Form 24-F shall be granted in Form 25-F and licences for manufacture of drugs against application in Form 24 shall be granted in form 25].
470-A. Form of loan5[licence to manufacture for sale or for distribution] of drugs other than those 6[specified in Schedules C, C(1) and X].- A loan 5[licence to manufacture for sale or for distribution] or drugs other than those 6[specified in Schedules C, C(1) and X] shall be issued in Form 25-A.
771. Conditions for the grant or renewal of a licence in Form 25 or 6[Form 25-F].- Before a licence in Form 25 6[or Form 25-F] is granted or renewed, the following conditions shall be complied with by the applicant.-
(1)The manufacture shall be conducted under the active direction and personal supervision of competent technical staff consisting at least of one person who is a whole-time employee and who is____
(a) a graduate in Pharmacy or Pharmaceutical Chemistry of 8[a University established in India by law or have an equivalent qualification recognized and notified by the Central Government for such purpose] of this rule and has had at least eighteen months practical experience after the graduation in the manufacture of drugs. This period of experience may, however, be reduced by six months if the person has undergone training in manufacture of drugs for a period of six months during his University course; or
(b) a graduate in Science of 8[a University established in India by law or have an equivalent qualification recognized and notified by the Central Government for such purpose] of his degree has studied Chemistry as a principal subject and has
___________________________________________________________________________________ 1Ins. by G.O.I. Notification No. F.1-20/64-D dt 26.10.1968. 2Subs. by G.O.I. Notification No. GSR 601(E0 dt 24.8.2001. 3Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 4Ins. by G.O.I. Notification No. F.1-16/57 D dt 15.6.1957 & No. F.1/22/59-D dt 9.4.1960. 5Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 6Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 7Amended by G.O.I. Notification No. F.1-16/57-D dt 15.6.1957 8Subs. by G.O.I. Notification No. GSR 71(E) dt 30.1.1987.
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had at least three years practical experience in the manufacture of drugs after his graduation; or
(c) a graduate in Chemical Engineering or Chemical Technology or Medicine of 1[a University established in India by law or have an equivalent qualification recognized and notified by the Central Government for such purpose] with general training and practical experience, extending over a period of not less than three years in the manufacture of drugs, after his graduation; or
2(d) holding any foreign qualification the quality and content of training of which are comparable with those prescribed in clause (a), clause (b) or clause (c) and is permitted to work as competent technical staff under this rule by the Central Government :
Provided that any person who was immediately before the 29th June, 1957, actively directing and personally supervising the manufacture of drugs and whose name was accordingly entered in any licence granted in Form 25 3[or Form 25-F] as it existed before the date shall be deemed to be qualified for the purposes of this rule.
4[Provided further that for drugs other than those specified in Schedule C, C(1) and X and meant for veterinary use, the whole-time employee under whose supervision the manufacture is conducted shall be graduate in veterinary Science or Pharmacy or General Science or Medicine of a University recognized by the Central Government and who has had at least three years practical experience in the manufacture of drugs excluding graduate in Pharmacy who shall have at least eighteen months practical experience in the manufacture of drugs].
5Provided 4[also] that the Licensing Authority may, in the matter of manufacture of disinfectant fluids, insecticides, liquid paraffin, medicinal gases, non chemical contraceptives, plaster of Paris and surgical dressings, for the manufacture of which the knowledge of Pharmaceutical chemistry or Pharmacy is not essential, permit the manufacture of the substance under the active direction and personal supervision of the competent technical staff, who, although not having any of the qualifications included in clauses (a), (b) or (c) of this rule, has, in the opinion of the Licensing Authority, adequate experience in the manufacture of such substance.
______________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 71(E) dt 30.1.1987. 2Added under Government of India Notification NO. F. 1-19/59-D, dated 13-6-1961. 3Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 4 Ins. by G.O.I. Notification No. GSR 93(E) dt 24.2.1999. 5 Added under Government of India, Ministry of Health, F. P. and U. D. Notification No. F. 1-14/68-D, dated the 26- 10-1968.
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(2)The factory premises shall comply with the conditions prescribed in Schedule M.
(3)The applicant shall provide adequate space, plant and equipment for the manufacturing operations; the space, plant and equipment recommended for various operations are given in Schedule M.
1(4)The applicant shall provide and maintain adequate staff, premises and laboratory equipment for carrying out tests of the strength, quality and purity of the substances at a testing unit, which shall be separate from the manufacturing unit and the head of the testing unit shall be independent of the head of the manufacturing unit :
Provided that the manufacturing units, which, before the commencement of the Drugs and Cosmetics (Amendment) Rules, 1977, were making arrangements with institutions approved by the Licensing Authority for such tests to be carried out on their behalf may continue such arrangements upto the 30th June, 1977 :
Provided further that for tests requiring sophisticated instrumentation techniques or biological or microbiological methods other than sterility the Licensing Authority may permit such tests to be conducted by institutions approved by it under Part XV(A) of these rules for this purpose.
2[(4A). The head of the testing unit referred to in condition (4) shall possess a degree in Medicine or Science or Pharmacy or Pharmaceutical chemistry of a University recognized for this purpose and shall have experience in the testing of drugs, which in the opinion of the licensing authority is considered adequate.]
(5)The applicant shall make adequate arrangements for the storage of drugs manufactured by him.
3(6)The applicant shall, while applying for a licence to manufacture patent or proprietary medicines, furnish to the Licensing Authority evidence and data justifying that the patent or proprietary medicines____
(i) contain the constituent ingredients in therapeutic / prephylactic quantities as determined in relation to the claims or conditions for which the medicines are recommended for use or claimed to be useful;
____________________________________________________________________________ 1Amended by G.O.I. Notification No. GSR 926 dt 16.7.1977. 2Ins. by G.O.I. Notification No. GSR 681(E) dt 5.12.1980. 3Ins. by G.O.I. Notification No. GSR 515 dt 10.4.1976.
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(ii) are safe for use in the context of the vehicles, excipients, additives and pharmaceutical aids used in the formulation and under the conditions in which the formulation for administration and use are recommended;
(iii) are stable under the conditions of storage recommended; and
(iv) contain such ingredients and in such quantities for which there is therapeutic justification.
1[v) have the approval, in writing, in favour of the applicant to manufacture drugs formulations falling under the purview of new drug as defined in rule 122-E, from the Licensing Authority as defined in Clause (b) of Rule 21.]
2[(7) The licensee shall comply with the requirements of Good Manufacturing practices as laid down in Schedule M.
371A. Conditions for the grant or renewal of a licence in Form 25B. ____Before a licence in Form 25-B is granted or renewed the following conditions shall be complied with by the applicant :____
(1) the repacking operation shall be carried out under hygienic conditions and under the supervision of a competent person;
4(2) the factory premises shall comply with the conditions prescribed in Schedule M; and
5(3) the applicant shall have adequate arrangements in his own premises for carrying out tests for the strength, quality and purity of the drugs at a testing unit which shall be separate from the repacking unit;
Provided that the repacking units, which before the commencement of the Drugs and Cosmetics (Second Amendment) Rules, 1977, were making arrangements with institutions approved by the licensing authority for such tests to be carried out on their behalf, may continue such arrangements upto the 31st July, 1977; ______________________________________________________________________________ 1Ins, by G.O.I. Notification No. GSR 311(E) dt 1.5.2002. 2Ins. by G.O.I. Notification No. GSR 735(E) dt 24.6.1988. 3Ins. by G.O.I. Notification No. F.1-22/59-D dt 9.4.1960. 4Amended by G.O.I. Notification No. S.O.2139 dt 12.8.1972. 5Amended by G.O.I. Notification No. GSR 926 dt 16.7.1977. .
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Provided further that for tests requiring sophisticated instrumentation techniques or biological or microbiological methods the licensing authority may permit such test to be conducted by institutions approved by it under Part XV(A) of these rules for this purpose.
Explanation.____A person who satisfies the following minimum qualifications shall be deemed to be a “competent person” for the purposes of rules 71-A or 74-A of these rules, namely:-
(a) a person who holds the Diploma in Pharmacy approved by the Pharmacy Council of India under the Pharmacy Act, 1948 (VIII of 1948) or a person who is registered under the said Act, or
(b) a person who has passed the Intermediate examination with Chemistry as one of the principal subjects or an examination equivalent to it or an examination recognized by the Licensing Authority as equivalent to it; or
(c) a person who has passed the Matriculation examination or an examination recognized by the Licensing Authority as equivalent to it and has had not less than four years practical experience in the manufacture, dispensing or repacking of drugs.
171-B : Conditions for the grant of renewal of a licence in Form 25-A.- Before a licence in form 25-A is granted or renewed, the applicant shall, while applying for a licence to manufacture patent or proprietary medicines, furnish to the Licensing Authority evidence and date justifying that the patent or proprietary medicines:
(i) contain the constituent ingredients in therapeutic/prophylactic quantities as determined in relation to the claims or conditions for which the medicines are recommended for use or claimed to be useful;
(ii) are safe for use in the context of the vehicles, recipients, additives and pharmaceutical aids used in the formulations and under conditions in which the formulations for administration and use are recommended;
(iii) are stable under the conditions of storage recommended; and
(iv)contain such ingredients and in such quantities for which there is therapeutic justification.
______________________________________________________________________________ 1Ins.by G.O.I. Notification No. GSR 515 dt 10.4.1976.
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172. Duration of licence.- An original licence or a renewed licence inform 25,2[Form 25-B or Form 25-F] unless sooner suspended or cancelled shall be 3[valid for a period of five years on and from the date on which] it is granted or renewed.
4Provided that if the application for the renewal of a licence is made before its expiry, or if the application is made within six months of its expiry, after payment of additional fee, the licence shall continue to be in force until orders are passed on for its renewal is not made within six months of its expiry.
2[73. Certificate of renewal.- The certificate of renewal of a licence in Form 25 or Form 25-F shall be issued in Form 26 or Form 26-F respectively].
573-A. A certificate of renewal of loan licence.- The certificate of renewal of a loan licence in Form 25-A shall be issued in Form 26-A.
673-AA. Duration of loan licence.- An original loan licence in Form 25-A or a renewed loan licence in Form 26-A, unless sooner suspended or cancelled, shall be 3[valid for a period of five years on and from the date on which] it is granted or renewed.
7Provided that if the application for the renewal of a licence is made before its expiry, or if the application is made within six months of its expiry, after payment of additional fee, the licence shall continue to be in force until orders are passed on for its renewal is not made within six months of its expiry.
873-B Certificate of renewal of licence in Form 25-B.- The certificate of renewal of a licence in Form 25-B shall be issued in Form 26-B.
__________________________________________________________________________ 1Amended by G.O.I. Notification No. F.1-10/62-D dt 10.4.1964. 2Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 3Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001. 4Amended by G.O.I. Notification No. S.O.2139 dt 12.8.1972. 5Amended by G.O.I. Notification No. F.1-10/62-D dt 10.4.1964 6Amended by G.O.I. Notification No. F.1-10/62-D dt 10.4.1964 7Amended by G.O.I. Notification No. S.O.2139 dt 12.8.1972. 8 Ins. by G.O.I. Notification No. F.1-22/59-D dt 9.4.1961.
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174. Conditions of licence in Form 25.____A licence in 2[Form 25 and Form 25-F] shall be subject to the conditions stated therein and to the following further conditions, namely :____
(a) the licensee shall provide and maintain staff, premises and the equipment as specified in rule 71;
(b) the licensee shall comply with the provisions of the Act and of these Rules and with such further requirements, if any, as may be specified in any rules subsequently made under Chapter IV of the Act; provided that where such further requirements are specified in the rules, these would come into force, four months after publication in the official Gazette;
(c) the license shall either in his own laboratory or in any other laboratory approved by the Licensing Authority under Part XV (A) of these rules test each batch or lot of the raw material used by him for the manufacture of his products and also each batch of the final product and shall maintain records or registers showing the particulars in respect of such tests as specified in Schedule U. The records or registers shall be retained for a period of 5 years from the date of manufacture;
(d) the licensee shall keep records of the details of manufacture as per particulars given in Schedule U of each batch of the drugs manufactured by him and such records shall be retained for a period of five years;
(e) the licensee shall allow an 3Inspector appointed under the Act, to enter, with or without prior notice, any premises and to inspect the plant and the process of manufacture and the means employed in standardizing and testing the drugs;
(f) the licensee shall allow an 3Inspector appointed under the Act to inspect all registers and records maintained under these rules and to take samples of the manufactured drugs and shall supply to such Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and the Rules thereunder have been observed;
(g) the licensee shall, from time to time, report to the Licensing Authority any changes in the expect staff responsible for the manufacture or testing of the drugs and any material alterations in the premises or plant used for the purpose which have been made since the date of the last inspection made on behalf of the licensing authority;
1 Amended by G.O.I. Notification No. F. 1-20/64-D, dated 26th October, 1968. 2. Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 3 Amended by G.O.I. Notification No. G.S.R. 444 dt. 28-4-1973.
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1(h) the licensee shall, on request, furnish to the Licensing Authority, the Controlling Authority or to such authorities as the Licensing Authority or the Controlling Authority may direct from every batch, or batches of drugs as the Licensing Authority or the Controlling Authority may from time to time specify, a sample of such quantity as may be considered adequate by such authority for any examination and, if so required, also furnish full protocols of tests which have been applied;
(i) if the Licensing Authority or the Controlling Authority so directs and if requested by the licensee who had also furnished prima facie reason for such directions, the licensee shall not sell or offer for sale any batch in respect of which a sample is or protocols are furnished under clause (h) until a certificate authorizing the sale of the batch has been issued to him by or on behalf of the Licensing Authority or the Controlling Authority;
(j) the licensee shall on being informed by the Licensing Authority or the Controlling Authority that any part of any batch of the drug has been found by the Licensing Authority or the Controlling Authority not to conform with the standards of strength, quality or purity specified in these rules and on being directed so to do, withdraw the remainder of the batch from sale, and, so far as may in the particular circumstances of the case be practicable, recall all issues already from that batch;
(k) the licensee shall maintain an Inspection Book in Form 35 to enable an Inspector to record his impressions and the defects noticed;
1(l) the licensee shall maintain reference samples from each batch of the drugs manufactured by him in a quantity which is at least twice the quantity of the drug required to conduct all the tests performed on the batch. In case of drugs bearing an expiry date on the label, the reference samples shall be maintained for a period of three months beyond the date of expiry or potency. In case of drugs where no date of expiry of potency is specified on the label, the reference samples shall be maintained for a period of three years from the date of manufacture.
2(m) The licensee, who has been granted a licence in Form 25-F, shall-
_____________________________________________________________________________ 1Amended /Ins by G.O.I. Notification GSR No. 444 dt 23.4.1973. 2Ins. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982.
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(i) forward to the licensing authority of the concerned States of manufacture and supply of the drug a statement of the sales effected to manufacturers, wholesalers, retailers, hospitals, dispensaries and nursing-homes and Registered Medical Practitioners every three months;
(ii) maintain accounts of all transactions giving details as indicated below in a register bound and serially page numbered and such records shall be retained for a period of five years or one year after the expiry of potency, whichever is later:-
A. Accounts of the drugs specified in Schedule X used for the manufacture:-
1. Date of issue 2. Name of the drug 3. Opening balance of stock on the production day. 4. Quantity received, if any, and source from where received. 5. Quantity used in manufacture. 6. Balance quantity on hand at the end of the production day. 7. Signature of the person in charge.
B. Accounts of production.:-
1. Date of manufacture, 2. Name of the drug, 3. Batch Number 4. Quantity of raw material used in manufacture. 5. Anticipated yield. 6. Actual yield, 7 Wastage, 8. Quantity of the manufactured goods transferred.
C. Accounts of the manufactured drugs:-
1. Date of manufacture, 2. Name of the drug, 3. Batch Number, 4. Opening Balance, 5. Quantity manufactured, 6. Quantity sold, 7. Name of the purchaser and his address, 8. Balance quantity at the end of the day, 9. Signature of the person in charge.
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(n) The licensee shall store drugs specified in Schedule X in bulk from and when any of such drug is required for manufacture in a place other than its place of storage it shall be kept in a separate place under the direct custody of a responsible person.]
1[(o) The licensee shall comply with the requirements of ‘Good Manufacturing Practices’ as laid down in Schedule M.]
74-A. Conditions for licence in Form 25-B.____A licence in Fom 25-B shall be subject to the conditions stated therein and to the following conditions :____
(a) the repacking of drugs shall at all times be conducted under the personal supervision of at least one person who is approved as a competent person by the Licensing Authority;
(b) the licensee shall either provide and maintain adequate arrangements in his own premises for carrying out tests of the strength, quality and purity of the drugs repacked or make arrangements with some institution approved by the Licensing Authority under Part XV (A) of these rules for such tests to be regularly carried out on his behalf by the institution;
(c) the licensee shall make adequate arrangements for the storage of drugs;
2 (d) the licensee shall comply with the provisions of the Act and of these Rules and with such further requirements, if any, as may be specified in any rules subsequently made under Chapter IV of the Act;
Provided that where such further requirements are specified in the rules, these would come into force four months after publication in the Official Gazette.
(e) the licensee shall allow any Inspector appointed under the Act to enter with or without notice, any premises where the packing of drugs in respect of which the licence is issued is carried on, to inspect the premises and to take samples of repacked drugs;
2(f) The licensee shall, either in his own laboratory or, in any other laboratory approved by the Licensing Authority, test each batch or lot of raw material used by him for repacking and also each batch of the product thus repacked and shall maintain records or registers showing the particulars in respect of such tests as specified in Schedule U. The records or registers shall be retained for a period
____________________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 735(E)dt 24.6.1988. 2 Amended by G.O.I. Notification No. F.1-20/64-D dt 26.10.1968
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of five years from the date of repacking. The licensee shall allow the Inspector to inspect all registers and records maintained under these rules and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and these Rules have been observed;
1(g) the licensee shall maintain an Inspection Book, in Form 35, to enable an Inspector to record his impressions and the defects noticed;
2(h) the licensee shall maintain reference samples from each batch of the drugs manufactured by him in a quantity which is at least twice the quantity of the drug required to conduct all the tests performed on the batch. In case of drugs bearing an expiry date on the label, the reference sample shall be maintained for a period of three months beyond the date of expiry of potency. In case of drugs where no date of expiry of potency is specified on the label, the reference samples shall be maintained for a period of three years from the date of manufacture.
374B. Conditions of licence in Form 25-A.____(1) The licence in Form 25-A shall be deemed to be cancelled or suspended, if the licence owned by the licensee in Form 25, whose manufacturing facilities have been availed of by the licensee, is cancelled or suspended, as the case may be, under these rules.
(2)The licensee shall comply with the provisions of the Act and of these Rules and with such further requirements if any, as may be specified in any rules subsequently made under Chapter IV of the Act; provided that where such further requirements are specified in the rules, these would come into force four months after publication in the Official Gazette.
(3)The licensee shall test each batch or lot of the raw material used by him for the manufacture of his products and also each batch of the final product and shall maintain records or registers showing the particulars in respect of such tests as specified in Schedule U. The records or registers shall be retained for a period of five years from the date of manufacture. The licensee shall allow an Inspector to inspect all registers and records maintained under these rules and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and these rules have been observed.
___________________________________________________________________________ 1Added under G.O.I. Notification No. 1-14/68-D, dt 26-10-68. 2Added under G.O.I. Notification No.G.S.R. 444 dt. 28-4-1973 . 3Amended under G.O.I. Notification No. F. 1-20/64-D, dated the 26th October, 1968.
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(4) The licensee shall either-
(i) provide and maintain to the satisfaction of the Licensing Authority adequate staff and adequate laboratory facilities for carrying out test of the strength, quality and purity of the substances manufactured by him or
(ii) make arrangements with some institution approved by the Licensing Authority under Part XV (A) of these rules for such tests to be regularly carried out on his behalf by the institution.
1(5) The licensee shall maintain reference samples from each batch of the drugs manufactured by him in a quantity which is at least twice the quantity of the drug required to conduct all the tests performed on the batch. In case of drugs bearing an expiry date on the label the reference samples shall be maintained for a period of three months beyond the date of expiry of potency. In case of drugs where no date of expiry of potency is specified on the label, the reference samples shall be maintained for a period of three years from the date of manufacture.
2 [(6) The licensee shall maintain an Inspection Book in Form 35 to enable an Inspector to record his impressions and the defects noticed.]
3 [75. Form of application for licence to manufacture for sale or distribution of drugs specified in Schedules C and C(1) and X 4[excluding those specified in Part XB] _ (1) Applications for the grant or renewal of licence to manufacture for sale or distribution of drugs specified in Schedules C and C(1) 4[excluding those specified in Part X-B and Schedule X], shall be made to the Licensing Authority in Form 27 and 5[shall be made upto ten items for each category of drugs catagorised in Schedule M and Schedule M-III and shall be accompanied by a licence of rupees six thousand and an inspection of rupees one thousand and five hundred for every inspection or for the purpose of renewal of licence.]
Provided that if the applicant applies for renewal of licence after its expiry but within six months of such expiry, the fee payable for renewal of the licence shall be 5[a licence fee of rupees six thousand plus an additional fee of rupees one thousand per month or a part thereof in addition to an inspection fee of rupees one thousand and five hundred.]
(2)Application for grant or renewal of licence to manufacture for sale or distribution of drugs specified in Schedules C, C(1) and X shall be made to the licensing authority in Form 27-B, and 5[shall be made up to ten items for each category of drugs categorized in Schedule M and
____________________________________________________________________________ 1 Ins. by G.O.I. Notification NO. GSR. No. 444, dt. 28-4-1973. 2 Ins. by G.O.I. Notification No. GSR 31(E) dt 8.5.1984. 3 Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 4 Subs. by G.O.I. Notification No. GSR 28(E) dt 22.1.1993. 5 Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001.
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Schedule M-III and shall be accompanied by a licence fee of rupees six thousand and an inspection fee of rupees one thousand five hundred for every inspection or for the purpose of renewal of licences:].
Provided that the applicant shall possess a licence in Form 28 to manufacture such drugs:
Provided further that if the application for renewal of a licence is made after its expiry but within six months of such expiry, the fee payable for renewal of the licence 1[shall be rupees six thousand plus an additional fee of rupees one thousand per month or part thereof in additional to an inspection fee of rupees one thousand five hundred.]
2[(3) The application for grant or renewal of licence to manufacture for sale or for distribution of drugs in ‘Large Volume Parenterals’ and ‘Sera and Vaccines’ shall be made to the licensing authority appointed under this Part in Form 27-D and 1[shall be made up to ten items for each category of drugs categorized in Schedule M and shall be accompanied by a licence fee of rupees six thousand and an inspection fee of rupees one thousand five hundred for every inspection or for the purposes of renewal of licences:]
Provided that if the application for renewal of a licence is made after its expiry but within six months of such expiry, the fee payable for renewal of the licence 1[shall be rupees six thousand plus an additional fee of one thousand per month or a part thereof in addition to the inspection fee of rupees one thousand and five hundred.]
1[(4) A fee of rupees one thousand shall be paid for duplicate copy of the licence issued under sub-rule (1), sub-rule (2) or sub-rule (3), as the case may be, if the original licence is defaced, damaged or lost.
(5) If the licence applies for manufacture of more than ten items of each category of drugs, the application shall be accompanied by an additional fee at the rate of rupees three hundred for each additional item of drugs categorized in Schedule M and Schedule M-III.]
3[(6) Where an application under this rule is for the manufacture of drug formulations falling under the purview of new drugs as defined in rule 122-E, such application shall also be accompanied with approval, in writing, in favour of the applicant, from the licensing authority as defined in clause (b) of rule 21.]]
___________________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001. 2 Ins. by G.O.I. Notification No. GSR 119(E) dt 11.3.1996. 3 Ins. by G.O.I. Notification No. GSR 311(E) dt 1.5.2002.
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175-A. Loan licences.____(1) Applications for the grant or renewal of loan 2[licences for the manufacture for sale or for distribution] of drugs specified in Schedules C and C(1) 3[excluding those specified in Part X-B and Schedule X] shall be made in Form 27-A to the licensing authority and 4[shall be made upto ten items for each category of drugs categorized in Schedule M and Schedule M-III and shall be accompanied by a fee of rupees six thousand and an inspection fee of rupees one thousand and five hundred for every inspection or for the purpose of renewal of licences.].
5Provided that if the applicant applies for the renewal of a licence after its expiry but within six months of such expiry the fee payable for renewal of the licence shall be 4[rupees six thousand and an inspection of fee of rupees one thousand five hundred plus an additional fee at the rate of rupees one thousand] per month or a part thereof.
Explanation. ____For the purpose of this rule a loan licence means a licence which a licensing authority may issue to an applicant who does not have his own arrangements for manufacture but who intends to avail himself of the manufacturing facilities owned by another licensee in Form 28.
(2) The licensing authority, shall, before the grant of a loan licence, satisfy himself that the manufacturing unit has adequate equipment, staff, capacity for manufacture and facilities for testing to undertake the manufacture on behalf of the applicant for a loan licence.
4[(3) Subject to the provisions of sub-rule (2), the application for manufacture of more than ten items of each category of drugs on a loan license, shall be accompanied by an additional fee at the rate of rupees three hundred for each additional item of drugs.
(4) If the licensing authority is satisfied that a loan licence is defaced, damaged or lot, he may, on payment of a fee of rupees one thousand, issue a duplicate copy of loan licence.]
75-B. [ Omitted as per G.O.I. Notification No. GSR 944(E) dt 21.9.1988.]
176. 6[Forms of licence to manufacture drugs specified in Schedules C and C(1), [excluding those specified in Part XB and Schedule X], or drugs specified in Schedules C, C(1) and X and the conditions for the grant or renewal of such licences.- 7[A licence to manufacture
____________________________________________________________________________ 1Ins. as per G.O.I. Notification No. F.1-16/57-D dt 15.6.1969. 2Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 3Subs. by G.O.I. Notification No. GSR 28(E) dt 22.1.1993. 4Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001. 5Amended by G.O.I. Notification No. S.O.2139 dt 13.8.1972 6Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 7 Subs. by G.O.I. Notification No. GSR 119(E) dt 11.3.1996.
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for sale or for distribution of drugs specified in Schedules C and C(1) other than Large Volume Parenterals, Sera and Vaccines, drugs specified in Part X-B and Schedule X shall be issued in Form 28 and a licence to manufacture for sale or distribution of drugs specified under Schedules C and C(1) (other than Large Volume Parenterals, Sera and Vaccines, drugs specified in Part X- B) and Schedule X shall be issued in Form 28-B. A licence to manufacture for sale or for distribution of Large Volume Parenterals, Sera and Vaccines shall be issued in Form 28-D. before a licence in Form 28 or Form 28-B or Form 28-D is granted or renewed, the following conditions shall be complied with by the applicant.]
(1) The manufacture will be conducted under the active direction and personal supervision of competent technical staff consisting at least of one person who is a whole time employee and who is____
(a) a graduate in Pharmacy or Pharmaceutical Chemistry of 1[a University established in India by law or has an equivalent qualification recognized and notified by the Central Government for such purpose] of this rule and has had at least eighteen months’ practical experience after the graduation in the manufacture of drugs to which this licence applies; this period of experience may however be reduced by six months if the person has undergone training in manufacture of drugs to which the licence applies for a period of six months during his University course; or
(b) a graduate in Science of 1[a University established in India by law or has an equivalent qualification recognized and notified by the Central Government for such purpose] of his degree has studied Chemistry or Microbiology as a principal subject and has had at least three years’ practical experience in the manufacture of drugs to which this licence applies after his graduation; or
(c) a graduate in Medicine of 1[a University established in India by law or has an equivalent qualification recognized and notified by the Central Government for such purpose] with at least three years’ experience in the manufacture and pharmacological testing of biological products after his graduation; or
2(d) a graduate in Chemical Engineering of a University recognized by the Central Government with at least three years’ practical experience in the manufacture of drugs to which this licence applies after his graduation; or
(e) holding any foreign qualification the quality and content of training of which are comparable with those prescribed in clause (a), clause (b), clause (c) or clause (d) and is permitted to work as competent technical staff under this rule by the Central Government.
______________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 71(E) dt 30.1.1987. 2Amended by G.O.I. Notification No. F.1-19/59-B dt 13.6.1961.
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Provided that any person who was approved by the licensing authority as an expert responsible for the manufacture of drugs for the purpose of rule 76 read with rule 78 as these rules were in force immediately before the 29th June, 1957, shall be deemed to be qualified for the purposes of this rule.
1Provided further that for the drugs specified in Schedules C and C(1) meant for veterinary use, the whole time employee under whose supervision the manufacture is conducted may be a graduate in Veterinary Science or general science or medicine or pharmacy of a University, recognized by the Central Government and who has had at least three years’ experience in the manufacture of biological products.
2[Provided further also that for the medical devices specified in Schedule C, the whole time employee under whose supervision the manufacture is conducted may be a Graduate in Science with Physics or Chemistry or Microbiology as one of the subjects; or graduate in Pharmacy; or Degree/Diploma holder in Mechanical or chemical or Plastic Engineering of a University recognized by the Central government for such purposes.]
(2) The factory premises shall comply with the conditions prescribed in Schedule M.2[and Schedule M-III in respect of medical devices].
(3) The applicant shall provide adequate space, plant and equipment for any or all the manufacturing operations; the space, plant and equipment recommended for various operations are given in Schedule M 2[and Schedule M-III].
2(4)The applicant shall provide and maintain adequate staff, premises and laboratory equipment for carrying out such tests of the strength, quality and purity of the substances as may be required to be carried out by him under the provisions of Part X of these rules including proper housing for animals used for the purposes of such tests, the testing unit being separate from the manufacturing unit and the head of the testing unit being independent of the head of the manufacturing unit :
Provided that the manufacturing units which before the commencement of the Drugs and Cosmetics (Amendment) Rules, 1977, were making arrangements with institutions approved by the Licensing Authority for such tests to be carried out on their behalf may continue such arrangements upto the 30th June, 1977 :
Provided further that for tests requiring sophisticated instrumentation techniques or biological or microbiological methods other than sterility the Licensing Authority may permit such tests to be conducted by institutions approved by it under Part XV (A) of these rules for this purpose. ___________________________________________________________________________ 1Ins. by G.O.I. Notification No. F.1-6/62-D dt 2.7.1969 2Ins. by G.O.I. Notification No. GSR 109(E) dt 22.2.1994.
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1[(4-A) The head of the testing unit referred to in condition (4) shall possess a degree in Medicine or Science or Pharmacy or Pharmaceutical Chemistry of a University recognized for this purpose and shall have experience in the testing of drugs, which in the opinion of the Licensing authority is considered adequate.]
(5) The applicant shall make adequate arrangements for the storage of drugs manufactured by him.
2(6)The applicant shall furnish to the Licensing Authority, if required to do so, data on the stability of drugs which are likely to deteriorate for fixing the date of expiry which shall be printed on the labels of such drugs on the basis of the data so furnished.
3(7)The applicant shall, while applying for licence to manufacture patent or proprietary medicines, furnish to the Licensing Authority evidence and data justifying that the patent or proprietary medicines :____
(i) contain the constituent ingredients in therapeutic/prophylactic quantities as determined in relation to the claims or conditions for which the medicines are recommended for use or claimed to be useful;
(ii) are safe for use in the context of the vehicles, excipients, additives and pharmaceutical aids used in the formulations and under the conditions in which the formulations for administration and use are recommended;
(iii) are stable under the conditions or storage recommended; and
(iv) contain such ingredients and in such quantities for which there is therapeutic justification.
4[(v) have the approval, in writing, in favour of the applicant to manufacture drug formulations falling under the purview of new drug as defined in rule 122-E, from the licensing authority as defined in clause (b) of rule 21.]
5[(8) The licensee shall comply, with the requirements of “Good Manufacturing Practices” as laid down in Schedule M.]
_____________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 681(E) dt 5.12.1980. 2Ins. by G.O.I. Notification No. GSR 444 dt 28.4.1973. 3Ins. byG.O.I. Notification No. GSR 515 dt 10.4.1976. 4 Ins. by G.O.I. Notification No. GSR 311(E) dt 1.5.2002. 5Ins. by G.O.I. Notification No. GSR 735(E) dt 24.6.1988.
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1[Explanation.- For the purpose of this rule, “Large Volume Parenterals” shall mean the sterile solutions intended for parenteral administration with a volume of 100 ml. or more (and shall include anti-coagulant solutions) in one container of the finished dosage from intended for single use.]
276-A : Form of loan licence to manufacture for sale 3[or for distribution] drugs specified in Schedules C and C(1) 4[excluding the drugs specified in Schedule X] and conditions for the grant or renewal of such licence :____A loan licence to manufacture for sale 3[or for distribution] drugs specified in Schedules C and C(1) 4[excluding the drugs, specified in Schedule X] shall be issued in Form 28-A, and the applicant shall, while applying for a licence to manufacture patent or proprietary medicines, furnish to the Licensing Authority evidence and date justifying that the patent or proprietary medicines;
(i) certain the constituent ingredients in therapeutic/prophylactic quantities as determined in relation to the claims or conditions for which the medicines are recommended for use or claimed to be useful;
(ii) are safe for use in the context of the vehicles, excipients, additives and pharmaceutical aids used in the formulations, and under the conditions in which the formulations for administration and use are recommended;
(iii) are stable under the conditions of storage recommended; and
(iv) contain such ingredients and in such quantities for which there is therapeutic justifications.
577. Duration of licence.____An original licence in 6[Form 28, Form 28-B and form 28-D or renewed licence informs 26, 26-F, and Form 26-H] or a renewed licence in Form 26, unless sooner suspended or cancelled shall be 7[valid for a period of five years on and from the date on which] it is granted or renewed:
____________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 119(E) dt 11.3.1996. 2Ins. by G.O.I. Notification No. GSR 515 dt 10.4.1976 3Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 4Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 5Amended by G.O.I. Notification No. G.1-10/62-D dt 10.4.1964. 6Subs. by G.O.I. Notification No. GSR 119(E) dt 11.3.1996. 7Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001.
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1Provided that if the application for the renewal of a licence is made before its expiry, or if the application is made within six months of its expiry after payment of additional fee, the licence shall continue to be in force until orders are passed on the application and the licence shall be deemed to have expired if the application for its renewal is not made within six months of its expiry.
278. Conditions of licence.____A licence in 3[Form 28, Form 28-B or form 28-D] shall be subject to the special conditions, if any, set out in Schedule F or Schedule F(1), as the case may be, which relate to the substance in respect of which the licence is granted and to the following general conditions____
(a) (i) The licence shall provided and maintain an adequate staff and adequate premises and plant for the proper manufacture and storage of the substances in respect of which the licence is issued;
(ii) Without prejudice to the generality of the foregoing requirement, every holder of a licence who for any purpose engaged in the culture or manipulation of pathogenic spore-bearing micro-organisms shall provide to the satisfaction of the Licensing Authority separate laboratories and utensils and apparatus required for the culture or manipulation of such micro-organisms, the laboratories, utensils and apparatus so provided not being used for the manufacture of any other substance;
4(b) The licensee shall provide and maintain staff, premises and equipment as specified in rule 76;
5(c) (i) The licensee shall maintain records of manufacture as per particulars given in Schedule U.
(ii) The licensee shall either in his own laboratory or in any laboratory approved by the Licensing Authority under Part XV (A) of these rules test each batch or lot of the raw material used by him for the manufacture of his product and also each batch of the final product and shall maintain records or registers showing the particulars in respect of such tests as specified in Schedule U. The records or registers shall be retained in the case of a substance for which a potency date is fixed for a period of two years from the expiry of such date, and in the case of other substances for a period of five years from the date of manufacture. ____________________________________________________________________________ 1Amended by G.O.I. Notification No. S.O. 2139 dt 12.8.1972. 2Amended by G.O.I. Notification No. F.1-6/62-B dt 2.6.1969. 3Subs. by G.O.I. Notification No. GSR 119(E) dt 11.3.1976. 4Amended by G.O.I. Notification No. F.1-16/57-D dt 15.6.1957 5Amended by G.O.I. Notification No. F.1-20/64-D dt 26.10.1968.
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(d) The licensee shall allow an 1Inspector appointed under the Act to enter, with or without prior notice, any premises where the manufacture is carried on and to inspect the premises, and in the case of substances specified in Schedules C and C(1), to inspect the plant and the process of manufacture and the means employed for standardizing and testing the substance;
(e) The licensee shall allow an 1Inspector appointed under the Act, to inspect all registers and records maintained under these rules and to take samples of the manufactured product and shall supply to such Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and Rules thereunder have been observed;
(f) The licensee shall from time to time report to the Licensing Authority any changes in the expert staff responsible for the manufacture or testing of the substance and any material alterations in the premises or plant used for that purpose which have been made since the date of the last inspection made on behalf of the Licensing Authority before the issue of the licence;
1(g) the licensee shall on request furnish to the Licensing Authority, Controlling Authority or to such authorities as the Licensing Authority or the Controlling Authority may direct, from every batch of drug as the licensing authority or the Controlling Authority may from time to time specify, a sample of such quantity as may be considered adequate by such Authority for any examination and, if so required, also furnish, full protocols of the tests which have been applied.
(h) If the Licensing Authority or the Controlling Authority so directs, the licensee shall not sell or offer for sale any batch in respect of which a sample is, or protocols are furnished under the last preceding sub-paragraph until a certificate authorizing the sale of the batch has been issued to him by or on behalf of the Licensing Authority or the Controlling Authority.
(i) The licensee shall on being informed by the Licensing Authority or the Controlling Authority that any part of any batch of the substance has been found by the Licensing Authority or the Controlling Authority not to conform with the standards of strength, quality or purity specified in these Rules and on being directed so to do, withdraw the remainder of that batch from sale and so far as may in the particular circumstances of the case be practicable recall all issues already made from that batch;
(j) No drug manufactured under the licence shall be sold unless the precautions necessary for preserving its properties have been observed throughout the period after manufacture;
(k) The licensee shall comply with the provisions of the Act and of these rules and with such further requirements, if any, as may be specified in any rules subsequently made under Chapter IV of the Act, provided that where such further requirements are specified in the rules, these would come into force four months after publication in the Official Gazette.
____________________________________________________________________________ 1Amended by G.O.I. Notification No. GSR 444 dt. 28.4.1973.
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1(l) The licensee shall maintain an Inspection Book in Form 35 to enable an Inspector to record his impression and defects noticed.
2(m) The licensee shall maintain reference samples from each batch of the drugs manufactured by him in a quantity which is at least twice the quantity of the drug required to conduct all the tests performed on the batch. In case of drugs bearing an expiry date on the label, the reference samples shall be maintained for a period of three months beyond the date of expiry of potency. In case of drugs where no date of expiry is specified on the label the reference samples shall be maintained for a period of three years from the date of manufacture.
3[(n)The licensee, who has been granted a license in Form 28-B shall-
(i) forward to the licensing authority of the concerned States of manufacture and supply of the drug a statement of the sales effected to manufacturers, wholesalers, retailers, hospitals, dispensaries and nursing- homes and Registered Medical Practitioners every three months
(ii) maintain accounts of all transactions giving details as indicated below in a register bound and serially page numbered and such records shall be retained for a period of five years or one year after the expiry of potency, whichever is later:-
A. Accounts of the drugs specified in Schedule X used for the manufacture:-
1. Date of issue 2. Name of the drug 3. Opening balance of stock on the production day. 4. Quantity received, if any, and source from where received. 5. Quantity used in manufacture. 6. Balance quantity on hand at the end of the production day. 7. Signature of the person in charge.
1Amended by G.O.I. Notification NO. F.1-14/68-B dt 26.10.1968. 2Ins. by .GO.I. Notification No. GSR 444 dt 28.4.1973. 3 Ins. by .GO.I. Notification No. GSR 462(E) dt 22.6.1982.
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B. Accounts of Production.:-
1. Date of manufacture, 2. Name of the drug, 3. Batch Number 4. Quantity of raw material used in manufacture. 5. Anticipated yield. 6. Actual yield, 7 Wastage, 8. Quantity of the manufactured goods transferred.
C. Accounts of the manufactured drugs:-
1. Date of manufacture, 2. Name of the drug, 3. Batch Number, 4. Opening Balance, 5. Quantity manufactured, 6. Quantity sold, 7. Name of the purchaser and his address, 8. Balance quantity at the end of the day,
(o) The licensee shall store drugs specified in Schedule X in bulk from and when any of such drug is required for manufacture in a place other than its place of storage it shall be kept in a separate place under the direct custody of a responsible person.]
1[(p) The licensee shall comply with the requirements of ‘Good Manufacturing Practices’ as laid down in Schedule M.]
278-A. Conditions of licence in Form 28-A.____ (1) The licence in Form 28-A shall be deemed to be cancelled or suspended, if the licence owned by the licensee in Form 28 whose manufacturing facilities have been availed of by the licensee is cancelled or suspended, as the case may be, under these rules.
__________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 735(E) dt 24.6.1998. 2Amended by G.O.I. Notification No. F.1-14/68-D dt 26.10.1968.
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(2) The licensee shall comply with the provisions of the Act, and of these rules and with such further requirements if any, as may be specified in any rules subsequently made under Chapter IV of the Act, provided that where such further requirements are specified in the rules, those would come into force four months after publication in the official Gazette.
(3) The licensee shall test each batch or lot of the raw material used by him for the manufacture of his products and also each batch of the final product and shall maintain records or registers showing the particulars in respect of such tests as specified in Schedule U. Records or registers shall be retained, in the case of a substance for which a potency date is fixed, for a period of two years from the expiry of such date and in the case of other substances, for a period of five years from the date of manufacture. The licensee shall allow an Inspector to inspect all registers and records maintained under these rules and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and these rules have been observed.
(4) The licensee shall either (i) provide and maintain to the satisfaction of the Licensing Authority adequate staff and adequate laboratory facilities for carrying out tests of the strength, quality and purity of the substances manufactured by him or (ii) make arrangements with some institution approved by the Licensing Authority for such tests to be regularly carried out on his behalf by the institution.
1(5)The licensee shall furnish to the Licensing Authority, if required to do so, data on the stability of drugs which are likely to deteriorate for fixing the date of expiry which would be printed on the labels of such drugs on the basis of the data so furnished.
1(6)The licensee shall maintain reference samples from each batch of the drug manufactured by him in a quantity which is at least twice the quantity of the drug required to conduct all the tests performed on the batch. In case of drugs bearing an expiry date on the labels, the reference samples shall be maintained for a period of three months beyond the date of expiry of potency. In case of drugs where no date of expiry of potency is specified on the label, the reference samples shall be maintained for a period of three years from the date of manufacture.
2[(7) The licensee shall maintain an Inspection Book in form 35 to enable an Inspector to record his impressions and the defects noticed.]
3[79. Inspection before grant or renewal of licence___Before a licence under this part is _____________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 444 dt 28.4.1973. 2Ins. by G.O.I. Notification No. GSR 331(E) dt 8.5.1984. 3Subs. by G.O.I. Notification No. GSR 923(E) dt 14.12.1992.
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granted or renewed the Licensing Authority or Central Licence Approving Authority, as the case may be, shall cause the establishment in which the manufacture is proposed to be conducted or being conducted to be inspected by one or more Inspectors appointed under this Act with or without an expert in the concerned filed. The Inspector or Inspectors shall examine all portions of the premises, plant and appliances and also inspect the process of manufacture intended to be employed or being employed along with the means to be employed or being employed for standardizing and testing the drugs to be manufactured or being manufactured and enquire into the professional qualifications of the Technical Staff to be employed. He shall also examine and verify the statements made in the application in regard to their correctness, and the capability of the applicant to comply with the requirements of competent technical staff, manufacturing plants, testing equipments and the ‘Requirements of Good Manufacturing Practices’ and the ‘Requirements of Plant and Equipment’ as laid down in Schedule M read with the Requirements of Maintenance of Records as laid down in Schedule U.
80. Report by Inspector.____The Inspector shall forward a detailed descriptive report giving his findings on each aspect of inspection along with his recommendations after completion of his inspection in accordance with the provisions of Rule 79, to the Licensing Authority or Central Licence Approving Authority, as the case may be.]
81. Procedure of Licensing Authority.____(1) If the Licensing Authority 1[or Central Licence Approving Authority, as the case may be,] after such further enquiry, if any, as he may consider necessary, is satisfied that the requirements of the Rules under the Act have been complied with and that the conditions of the licence and the Rules under the Act will be observed, he 2[shall issue a licence under this Part].
(2) If the Licensing Authority 1[or Central Licence Approving Authority, as the case may be,] is not so satisfied, he shall reject the application and shall inform the applicant of the reasons for such rejection and of the conditions which must be satisfied before a licence can be granted and shall supply the applicant with a copy of the inspection report.
382. Further application after rejection.____If within a period of six months from the rejection of an application for a licence the applicant informs the Licensing Authority 1[or Central Licence Approving Authority, as the case may be,) that the conditions laid down have been satisfied and deposits an inspection 4[fee of rupees two hundred and fifty] the Licensing Authority 1[or Central Licence Approving Authority, as the case may be,]may, if after causing a further inspection to be _____________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 923(E) dt 14.12.1992. 2Subs. by G.O.I. Notification No. GSR 119(E) dt 11.3.1996. 3Ins. by G.O.I. Notification No. F.1-16/57-D dt 15.5.1959. 4Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001.
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made, he is satisfied that the conditions for the grant of a licence have been complied with, 1[in respect of drugs notified under Rule 68-A] issue a licence in Form 28 2[or Form 28-B].
83. Renewal.____On application being made for renewal, the licensing authority may cause an inspection to be made and, if satisfied that the condition of the licence and the Rules under the Act are, and will continue to be observed, 3[he shall prepare a report to that effect in respect of those drugs which have been notified by the Central Government under Rule 68-A and forward it along with the application to the Central Licence Approving Authority], and 4[he shall issue a certificate of renewal under this Part].
583-A. Certificate of a renewal of a loan licence.____The certificate of renewal of a loan licence in Form 28-A shall be issued in Form 26-A.
683-AA. Duration of loan licence.____An original loan licence in Form 28-A or a renewed loan licence in Form 26-A, unless sooner suspended or cancelled, shall be 7[valid for a period of five years on and from the date on which] it is granted or renewed.
6Provided that if the application for the renewal of a licence is made before its expiry, or if the application is made within six months of its expiry, after payment of the additional fee, the licence shall continue to be in force until orders are passed on the application and the licence shall be deemed to have expired if the application for its renewal is not made within six months of its expiry.
84. The provisions of this Part shall apply to the manufacture of drugs for sale notwithstanding that such drugs are manufactured for sale outside India.
3[84-A. Provision for appeal to the State Government or Central Government by party whose licence has not been granted or renewed.- Any person who is aggrieved by the order passed by the Licensing Authority or the Central Licence Approving Authority, as the case may be, refusing to 4[grant or renew a licence under this Part], may within thirty days from the date of receipt of such order, appeal to the State Government or Central Government, as the case may be, and the State Government or the Central Government may, after such enquiry into the matte, ___________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 923(E) dt 14.12.1992. 2Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982 3Subs. by G.O.I. Notification No. GSR 923(E) dt 14.12.1992. 4Subs. by G.O.I. Notification No. GSR 119(E) dt 11.3.1996.. 5Ins. by G.O.I. Notification No. F1-16/57-B dt 15.6.1959. 6Amended by G.O.I. Notification No. S.O.2139 dt 12.8.1972. 7Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001
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as is considered necessary and after giving the said person an opportunity for representing his views, may pass such order in relation thereto as it thinks fit.] .
84-AA Additional information to be furnished by an applicant for licence or a licensee to the licensing authority.____The applicant for the grant of a licence or any person granted a licence under this Part s hall, on demand, furnish to the Licensing Authority before the grant of the licence or during the period the licence is in force, as the case may be, documentary evidence in respect of the ownership or occupation on rental or other basis of the premises, specified in the application for licence or in the licence granted, constitution of the firm or any other relevant matter which may be required for the purpose of verifying the correctness of the statements made by the applicant or the licensee, while applying for or after obtaining the licence, as the case may be.
184-B. Prohibition for the manufacture for sale of cyclamates and preparations containing cyclamates. ____No person shall manufacture for sale cyclamates and preparations containing cyclamates.
2[85. Cancellation and suspension of licences.____(1) The Central Licence Approving Authority may, after giving the licensee an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefor, cancel a licence issued under this Part, or suspend it for such period as he thinks fit either wholly or in respect of any of the drugs to which it relates 3[or direct the licensee to stop manufacture, sale or distribution of the said drugs and an Inspector], if in his opinion, the licensee has failed to comply with any of the conditions of the licencee or with any provisions of the Act or rules made thereunder.
(2) The Licensing Authority may, for such licences granted or renewed by him, after giving the licensee an opportunity to show cause why such an order should not be passed, by an order in writing stating the reason therefor, cancel a licence issued under this Part or suspend it for such period as he thinks fit, either wholly or in respect of some of the substances to which it relates, 3[or direct the licensee to stop manufacture, sale or distribution of the said drugs and an Inspector] if, in his opinion, the licensee has failed to comply with any of the conditions of the licence or with any provision of the Act or Rules thereunder.
4[(3) A licensee whose lice has been suspended or cancelled by the Central Licence Approving Authority or Licensing Authority under sub-rule (1) or sub-rule (2), as the case may ____________________________________________________________________________ 1Ins. by G.O.I. Notification No. S.O.2358 dt 26.8.1972. 2Subs, by G..O.I. Notification No. GSR 923(E) dt 14.12.1992 3Subs. by G.O.I. Notification No. GSR 20(E) dt 11.1.1996. 4 Ins. by G.O.I. Notification No. 615(E) dt 9.8.1994.
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be, may within ninety days of the receipt of a copy of the order by him prefer an appeal to the Central Government or the State Government, as the case may be, and the Central Government or the State Government may after giving the licensee an opportunity of being head, confirm, reverse or modify such order.]
1PART VII-A 2[MANUFACTURE FOR SALE OR FOR DISTRIBUTION] OF HOMOEOPATHIC MEDICINES
85-A. Manufacture on more than one set of premises.____If Homoeopathic medicines are manufactured in more than one set of premises a separate application shall be made and a separate licence shall be obtained in respect of each such set of premises.
85-B. Application for licence to manufacture Homoeopathic medicines.____(1) Application for grant or renewal of licences to manufacture for sale 2[or for distribution] of Homoeopathic medicines shall be made to the Licensing Authority appointed by the State Government for the purpose of this Part (hereinafter in this Part referred to as the Licensing Authority) and shall be made in Form 24-C.
3(2) The application in Form 24-C shall be accompanied
(a) by a fee of 4[rupees two hundred] for the manufacture of Homoeopathic mother tinctures and potentised preparations and an inspection fee of 4[rupees one hundred] ten for the first inspection or 4[rupees fifty] in case of inspection for renewal of licence;
(b) by a fee of rupees two hundred for the manufacture of Homoeopathic potentised preparations only, and an inspection fee of rupees one hundred for the first inspection or rupees fifty e in case of inspection for renewal of licence;
(c) by a fee of rupees 4[two hundred] for the manufacture of potentised preparation from back potencies by pharmacies which are already licensed to sell Homoeopathic medicines by retail and an inspection fee of rupees 4[one hundred] for the first inspection or 4[rupees fifty] in case of inspection for renewal of licence.
____________________________________________________________________ 1Added under G.O.I.Notification No. F. 1-35/64-D, dtd 18.8.1964. 2 Ins. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985. 3 Amended G.O.I. Notification No. G.S.R. 245 dtd 11-2-1976. 4 Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001.
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1(3) If a person applies for renewal of a licence after its expiry but within six months of such expiry, the fee payable for the renewal of such a licence shall be____
(a) 2[rupees two hundred] plus an additional fee at the rate of 2[rupees one hundred] per month or part thereof and an inspection fee of 2[rupees fifty] for the manufacture of Homoeopathic mother tinctures and potentised preparations;
(b) 2[rupees two hundred] plus an additional fee at the rate of 2[rupees one hundred] per month or part thereof and an inspection fee of 2[rupees fifty] for the manufacture of Homoeopathic potentised preparations only;
(c) 2[rupees two hundred] plus an additional fee at the rate of 2[rupees one hundred] per month or part thereof and an inspection fee of 2[rupees fifty] for the manufacture of Homoeopathic mother tinctures and potentised preparations from back potencies by pharmacies who are already licensed to sell Homoeopathic medicines by retail.]
(4) A fee of 2[rupees fifty] shall be paid for a duplicate copy of the licence for the manufacture of Homoeopathic mother tinctures and potentised preparations issued under sub- rule (1) if the original is defaced, damaged or lost. While the fee to be paid for such a duplicate copy of the licence for the manufacture of Homoeopathic potentised preparations only shall be [2rupees fifty].
3[(5) Applications by licensee to manufacture additional items of Homoeopathic medicines shall be made to the Licensing Authority and such applications shall be accompanied by a fee of 2[rupees fifty] for each additional item.]
85C. Application to manufacture ‘New Homoeopathic medicines’____Subject to the other provisions of these Rules____
(1) no ‘New Homoeopathic medicine’ shall be manufactured unless it is previously approved by the Licensing Authority mentioned in rule 21;
(2) the manufacturer of ‘New Homoeopathic medicine’, when applying to the Licensing Authority mentioned in sub-rule (1) shall produce such documentary and other evidence as may be required by the Licensing Authority for assessing the therapeutic efficacy of the medicine including the minimum provings carried out with it.
__________________________________________________________________________ 1 Amended by G.O.I Notification No. GSR 245 dt 11.2.1976. 2 Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001. 3 Ins. by G.O.I. Notification No. GSR 13(E) dt 7.1.1993.
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(3) While applying for a licence to manufacture a ‘New Homoeopathic medicine’ an applicant shall produce along with his application evidence that the ‘New Homoeopathic medicine’ for the manufacture of which application is made has already been approved.
Explanation.____The term ‘New Homoeopathic medicine’ in this rule shall have the same meaning as in rule 30-AA.
185-D. Form of licence to manufacture Homoeopathic medicines.____Licence for manufacture of Homoeopathic medicines is a licence to manufacture potentised preparations from back potencies by Pharmacies who are already licensed to sell Homoeopathic medicines by retail and shall be granted in Form 25-C.
85-E. Conditions for the grant or renewal of a licence in Form 25-C.____Before a licence in Form 25-C is granted or renewed the following conditions shall be complied with by the applicant :____
(1)The manufacture of Homoeopathic medicines shall be conducted under the direction and supervision of competent technical staff consisting at least of one person who is a whole time employee 2[and who is ____
a) a graduate in Science with Chemistry as one of the subjects with three years’ experience in manufacture of Homoeopathic Medicines; or
b) a graduate in Pharmacy with 18 months of experience in the manufacture of Homoeopathic medicines; or
c) holds qualification as defined under sub-clause (g) of clause (1) of Section 2 of Homoeopathy Central Council Act, 1973 (59 of 1973) with 18 months of experience in the manufacture of Homoeopathic medicines.
Provided that the persons who are already in employment with five years’ experience in the manufacture of Homoeopathic medicines and whose name was accordingly entered in any licence granted in Form 25-C for manufacture of different classes of Homoeopathic medicines included in them shall be deemed to be qualified for the purpose of this rule.]
3[(2) The factory premises shall comply with the requirements and conditions specified in Schedule M-I :
_____________________________________________________________________ 1Amended by G.O.I.. Notification No.F.1-59/68-D dt 19.11.1969. 2Subs. by G.O.I. Notification No. GSR 812(E) dt 14.11.1994. 3Subs. by G.O.I. Notification No. GSR 570(E) dt 12.6.1987 .
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Provided that where the Licensing Authority considers it necessary or expedient so to do, it may having regard to the nature and extent of manufacturing operations, relax or suitably alter the said requirements or conditions in any particular case for reasons to be recorded in writing.]
(3) The applicant for manufacture of Homoeopathic mother tinctures shall either (i) provide and maintain adequate staff, premises and laboratory equipment for identifying the raw materials and for testing the mother tinctures wherever possible, or (ii) make arrangements with some institution approved by the Licensing Authority under Part XV(A) of these rules for such tests, wherever possible, to be regularly carried out on his behalf by that institution.
(4) The premises where Homoeopathic medicines are manufactured shall be distinct and separate from the premises used for residential purposes.
(5) Homoeopathic medicines shall not be manufactured simultaneously with drugs pertaining to other systems of medicine.
(6) The applicant shall make arrangements for proper storage of Homoeopathic medicines manufactured by him.
1Provided that in case potentised preparations are made in a Pharmacy holding licence in Form 20-C, the conditions (2) and (3) shall not apply. The licensee shall ensure to the satisfaction of the Licensing Authority that the products manufactured by it, conform to the claims made on the label.]
2[85-EA Inspection before grant or renewal of licence.- Before a licence under this Part is granted or renewed in Form 25-C or Form 26-C, the Licensing Authority shall cause the establishment, in which the manufacture is proposed, to be conducted or being conducted, to be inspected by one or more Inspectors appointed under the Act. The Inspector or Inspectors shall examine all portions of the premises, plant and appliances and also inspect the process of manufacture intended to be employed or being employed along with the means to be employed or being employed for standardizing and testing the substances to be manufactured and inquire into the professional qualifications of the technical staff to be employed. He shall also examine and verify the statements made in the application in regards to their correctness, and the capability of the applicant to comply with the requirements of competent technical staff, manufacturing plants, testing equipments and the requirements of plant and equipment as laid down in Schedule M-I read with the requirements of maintenance of records as laid down in Schedule U. _____________________________________________________________________________ 1 Amended by G.O.I. Notification No. F.1-59/68-D dt 19.11.1969. 2 Ins. by G.O.I. Notification No. GSR 493(E) dt 9.6.1995.
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85-EB Report by Inspector.- The Inspector or Inspectors shall forward a detailed descriptive report giving his or their findings on each aspect of inspection along with his or their recommendations after completion of his or their inspection to the Licensing Authority.
85-EC.Grant or refusal of licence.- (1) If the Licensing Authority after such further enquiry, if any, as he may consider necessary is satisfied that the requirements of the rules under the Act have been complied with and that conditions of the licence and the rules under the Act shall be observed, he shall grant or renew a licence in Form 25-C or Form 26-C.
(2) If the Licensing Authority is not so satisfied, he shall reject the application and shall inform the applicant of the reasons for such rejection and of the conditions which must be satisfied before a licence can be granted or renewed and shall supply the applicant with a copy of inspection report.
85-ED. Further application after rejection.- If with a period of six months from the rejection of an application for a licence, the applicant informs the Licensing Authority that the conditions laid down have been fulfilled and deposits an inspection fee of 1[rupees two hundred and fifty], the Licensing Authority may, if, after causing further inspection to be made, he is satisfied that the conditions for the grant of licence have been complied with, issue a licence in Form 25-C or Form 26-C.
85-EE Appeal to the State Government.- Any person who is aggrieved by the order passed by the Licensing Authority refusing to grant or renew a licence under this Part may within ninety days from the date of receipt of such order, appeal to the State Government and the State Government may, after such enquiry into the matter as is considered necessary and after giving the said person an opportunity for representing the case, pass such order as it thinks fit.]
85-F. Duration of licence.____An original licence or a renewed licence unless it is sooner suspended or cancelled shall be 1[valid for a period of five years on and from the date on which] it is granted or renewed:
2Provided that if the application for renewal of a licence in force is made before its expiry or if the application is made within six months of its expiry, after payment of additional fee, the licence shall continue to be in force until orders are passed on the application and the licence shall be deemed to have expired if application for its renewal is not made within six months of its expiry.
1 Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001. 2Amended by G.O.I. Notification No. S.O.2139 dtd 12-8-1972. .
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85-G.Certificate of renewal.____The certificate of renewal of a licence in Form 25-C shall be issued in Form 26-C.
85-H. Conditions of licence.____A licence in Form 25-C shall be subject to the conditions stated therein and to the following further conditions, namely :___
(a) the licensee shall provide and maintain staff and premises as specified in rule 85-E;
(b) the licensee shall allow an 1Inspector appointed under the Act to enter, with or without prior notice, any premises where the manufacture of a Homoeopathic medicine in respect of which the licence is issued is carried on, to inspect the premises and to take samples of the manufactured Homoeopathic medicines;
(c) the licensee shall allow an Inspector to inspect all registers and records maintained under these rules and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and the Rules made thereunder have been observed;
2(d) the licensee shall maintain an Inspection Book in Form 35 to enable an Inspector to record his impressions and defects noticed;
(e) the licensee shall comply with the following conditions in respect of mother tinctures manufactured by him_
(i) the crude drug used in the manufacture of the mother tincture shall be identified and records of such identification shall be kept 3[for a period of five years].
(ii) the total solids in the mother tincture shall be determined and records of such tests shall be kept 3[for a period of five years].
(iii) the alcohol content in the mother tincture shall be determined and records of the same shall be maintained 3[for a period of five years].
(iv) the containers of mother tinctures shall preferably be of glass and shall be clean and free from any sort of impurities or adhering matter. The glass shall be neutral as far as possible.
(v) in the process of manufacture of mother tinctures hygienic conditions shall be scrupulously observed by the licensee. Storage and handling conditions shall also be properly observed by the licensee according to Homoeopathic principles.
_____________________________________________________________________________ 1Amended by G.O.I. Notification No. G. S. R. 444 dtd 28-4-1973. 2Amended by G.O.I. Notification No. F-1-14/ 68-D, dated 26-10-68. 3Ins. by .O.I. Notification No. GSR 13(E) dt 7.1.1983.
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1[(ea) no colour shall be added to any Homoeopathic medicines : Provided that caramel may beaded to combination of Homoeopathic preparations with syrup base;]
(f) records shall be maintained of Homoeopathic medicines containing alcohol and the quantities sold together with names and addresses of parties to whom sold.2 [Such records shall be maintained for a period of five years.]
385-HH Additional information to be furnished by an applicant for the licence or a licensee to the Licensing Authority.-The applicant for the grant of licence or any other person granted a licence under this Part shall, on demand, furnish to the Licensing Authority, before the grant of the licence or during the period the licence is in force, as the case may be, documentary evidence in respect of the ownership or occupation in rental or other basis of the premises, specified in the application for licence or in the licence granted, constitution of the firm or any other relevant matters which may be required for the purpose of verifying the correctness of the statements made by the applicant or the licensee, while applying for or after obtaining the licence, as the case may be.
85-I. Cancellation and suspension of licences._____(1) The Licensing Autority may, after giving the licensee an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefore, cancel a licence issued under this Part or suspend it for such period as he thinks fit, either wholly or in respect of some of the substances to which it relates if, in his opinion, the licensee has failed to comply with any of the conditions of the licence or with any provisions of the Act or Rules made thereunder.
4(2) A licensee whose licence has been suspended or cancelled may, within three months of the date of the order under sub-rule (1), prefer an appeal against that order to the State Government, which shall decide the same.
PART VIII___ MANUFACTURE FOR EXAMINATION, TEST OR ANALYSIS
86. Conditions relating to manufacture for examination, test or analysis____The provisions of Section 18 of the Act shall not apply to the manufacture of any drug in small quantities for the purpose of examination, test or analysis if the conditions prescribed in this Part are fulfilled.
___________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 680(E) dt 5.12.1980 . 2Ins. by G.O.I. Notification No. GSR 13(E) dt 7.1.1983. 3Added by G.O.I. Notification No. S. O. 2139 dtd 12-8-1972. 4Amended G.O.I. Notification No. G SR. 926 dtd 16-7-1977.
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87.Labelling.____Any drug manufactured for the purpose of examination, test or analysis shall be kept in containers bearing labels indicating the purpose for which it has been manufactured.
88.Labelling of drugs supplied to other persons.____If any drug manufactured for the purpose of examination, test or analysis is supplied by the manufacturer to any other person, the container shall bear a label on which shall be stated the name and address of the manufacturer, the accepted scientific name of the substance if known, or if not known a reference which will enable the substance to the identified and the purpose for which it has been manufactured.
89.Licence.____If the person proposing to manufacture a drugs for the purpose of examination, test or analysis does not hold a licence in Form 25 or Form 28 in respect of such drugs he shall, before commencing such manufacture, obtain a licence in Form 29.
1Provided that in the case of a drug the composition of which is such that the drug is not generally recognized among experts qualified by scientific training and experience to evaluate the safety of drugs as safe for use, no licence in Form 29 shall be granted unless the applicant produces a certificate from the “Licensing Authority” mentioned in rule 21, to the effect that there would be no objection to such licence being granted.
90. Form of application.____(1) An application for a licence in Form 29 shall be made to the Licensing Authority appointed by the State Government for the purpose of this Part (hereafter in this Part referred to as the Licensing Authority) in Form 30 and shall be made by or countersigned by the head of the institution in which, or a director of the firm or company by which, the substance will be manufactured.
2(2) Every application in Form 29 shall be accompanied by a fee of 3[rupees two hundred fifty.].
91. Duration of licence.____A licence in Form 29 shall, unless sooner cancelled, be in force for a period of one year from the date of issue, and may thereafter be renewed for periods of one year at a time.
92. Conditions of licence.____A licence in Form 29 shall be subject to the following conditions____
(a) the licensee shall use the drugs manufactured under the licence exclusively for purpose of examination, test or analysis, and shall carry on the manufacture and examination, test or analysis at the place specified in the licence;
____________________________________________________________________________ 1Added under G.O.I. Notification No. F. 1-19/59-D, dtd 13-6-1961. 2Added by G.O.I. Notification No. S. O. 903 dtd 28-2-1976 3 Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001
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(b) the licensee shall allow any 1Inspector appointed under the Act to enter, with or without notice, the premises where the drugs are manufactured and to satisfy himself that only examination, test or analysis work is being conducted;
(c) the licensee shall keep a record of the quantity of drugs manufactured for examination, test or analysis and of any person or persons to whom the drugs have been supplied;
(d) the licensee shall comply with such further requirements, if any, applicable to the holders of licences in Form 29 as may be specified in any Rules subsequently made under the Act and of which the Licensing Authority has given him not less than one month’s notice;
(e) the licensee shall maintain an Inspection Book to enable an Inspector to record his impressions and defects noticed.
93. Cancellation of licences.____(1) The Licensing Authority may after giving the licensee an opportunity to show cause why such an order should not be passed, by an order in writing stating the persons therefore, cancel a licence issued under this Part, either wholly or in respect of some of the substances to which it relates, if, in his opinion, the licensee has failed to comply any of the conditions of the licence or with any provisions of the Act or Rules thereunder.
1(2) A licensee whose licence has been suspended or cancelled may appeal to the State Government within three months of the date of the order.
PART IX LABELLING AND PACKING OF DRUGS OTHER THAT
HOMOEOPATHIC MEDICINES
94. Exemption of certain drugs from certain provisions of this Part— (1) Labels on packages or containers of drugs for export shall be adapted to meet the specific requirements of the law of the country to which the drug is to be exported but the following particulars shall appear in a conspicuous position on the innermost container in which the drug is packed and every other covering in which that container is packed:
(a) name of the drug; (b) the name, address of the manufacturer and the number of the licence under which
the drug has been manufactured; (c) batch or lot number; (d) date of expiry, if any.
___________________________________________________________________________ 1 Amended by G.O.I. Notification No. F.1-10/68-D, dtd 17.6.1969.
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1[Provided that where a drug, not classified under Schedule F, Schedule F(1) and Schedule X, blood products, Narcotic and Psychotropic Substances is required by the consignee to be not labeled with the name and address of the manufacturer, the labels on packages or containers shall bear a code number as approved by the Licensing Authority mentioned in rule 21.]
2(2) The provisions of rules 96 to 101 inclusive, shall not apply to a medicine made up ready for treatment, whether after or without dilution, which is supplied on the prescription of a registered practitioner provided that:
(i) the medicine is labelled with the following particulars :---
(a) The name and address of the supplier; (b) The name of the patient and the quantity of the medicine; (c) The number representing serial number of the entry in the prescription register; (d) The dose, if the medicine is for internal use; 3[(e) The words ‘FOR EXTERNEL USE ONLY’ if the medicine is for external application].
(ii) Condition (3) of the conditions in rule 65 is satisfied.
95. Prohibition of sale or distribution unless labelled.—Subject to the other provisions of these Rules, no person shall sell or distribute any drug (including a patent or proprietary) unless it is labelled in accordance with these Rules.
496. Manner of Labelling :--- (1) Subject to the other provisions of these rules, the following particulars shall be either printed or written in indelible ink and shall appear in a conspicuous manner on the label of the innermost container of any drug and on every other covering which the container is packed, namely : ---
(i) The name of the drug 5[(A) For this purpose, the proper name of the drug shall be printed or written in a more conspicuous manner than the trade name, if any, which shall be shown immediately after or under the proper name and shall be]—
(a) for drugs included in the Schedule F or Schedule F (1), the name given therein;
__________________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 676(E) dt 2.6.1988. 2Amended by G.O.I. Notification No. F.1-19/59-D, dtd 13-6-1961. 3Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982. 4Amended under G.O.I. Notification No. GSR19 dt 7-1-1978 5Subs. by G.O.I. Notification No. GSR 27(E) dt 17.1.1981.
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(b) for drugs included in the India Pharmacopoeia or the official pharmacopoeia and official compendia of drug standards prescribed in the rule 124, the name or synonym specified in the respective official pharmacopoeias and official compendia of drug standards followed by the letters ‘I.P., or, as the case may be, by the recognized abbreviations of the respective official pharmacopoeias and official compendia of drug standards;
(c) for drugs included in the National Formulary of India, the name or synonym specified therein followed by the letters ‘N.F.I.’;
(d) for other drugs, the international non-proprietary name, if any, published by the World Health Organisation or where an international non-proprietary name is not published, the name descriptive of the true nature or origin of the substance;
[ Clause B inserted by Notification No. GSR 27(E) dt 17.1.81 was deleted as per G.O.I. Notification No. GSR 94(E) dt 8.2.2000.
(ii) A correct statement of the net content in terms of weight, measure, volume, number of units of contents, number of units of activity, as the case may be, and the weight, measure and volume shall be expressed in Metric system.
(iii) The content of active ingredients.
This shall be expressed---
(a) for oral liquid preparations in terms of the content per single dose being indicated in 5 milliliters 1[** *] :
Provided that where the dose is below 5 milliliters the contents of active ingredients may be expressed in terms of one milliliter;2[or fraction thereof.]
1[Provided further that where the single dose is more than 5 milliliters, the content of active ingredients shall be expressed in terms of minimum single dose as approved by the licensing authority.]
(b) for liquid parenteral preparations ready for administration in terms of 1 milliliters or percentage by volume or per dose in the case of single dose container :
_____________________________________________________________________________ 1Amended/Inserted by G.O.I. Notification No. GSR 285(E) dt 16.7.1996. 2Ins. by G.O.I. Notification No. GSR 681(E) dt 5.12.1980.
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Provided that if the preparation is contained in an ampoule it will be enough of the composition is shown on the label or wrapper affixed to any package in which such ampoule is issued for sale;
(c) for drugs in solid form intended for parenteral administration, in terms of units or weight per milligram or gram;
(d) For tablets, capsules, pills and the like, in terms of the content in each tablet, capsule, pill or other unit, as the case may be;
(e) for other preparations, in terms of percentage by weight or volume or in terms of unitage per gram or milliliter, as the case may be:
Provided that clause (iii) shall not apply to the pharmacopoeial preparations where the composition of such preparation where the composition of such preparation is specified in the respective pharmacopoeia and to a preparation included in the National Formulary of India;
(iv) 1[The name of the manufacturer and the address of the premises of the manufacturer where the drug has been manufactured.]
Provided that of the drug is contained in an ampoule or a similar small container, it shall be enough if only the name of the manufacturer and his principal place of 1[manufacture] is shown;
(v) A distinctive batch number, that is to say, the number by reference to which details of manufacture of the particular batch from which the substance in the container is taken are recorded and are available for inspection, the figure representing the batch number being preceded by the words ‘Batch No.’ or ‘B. No.’ or ‘Batch’ or ‘Lot No.’ or ‘Lot’;
NOTE (1) In the case of drugs manufactured by a continuous process, like manufacture of
magnesium sulphate, pharmaceutical chemicals etc., the production resulting in one homogenous mix of the finished products shall be considered as one “Batch”.
(2) In the case of powders, liquid orals, ointments etc., one “Batch Number” shall be assigned to all the containers filled from one homogenous bulk.
__________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 491(E) dt 25.7.1991.
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(3) In the case of tablets, capsules, lozenges, troches, etc., one “Batch Number” shall be assigned to the products manufactured from one homogenous mix ready for compression or filling.
(4) In the case of parenteral preparations sterilized by steam under pressure, one “Batch Number” shall be assigned to all containers filled from one homogenous bulk solution and sterilized in one sterilizer load.
(5) In the case of containers of parenteral preparations filled from one homogenous bulk solution and sterilized in more than one sterilizer load, the “Batch Number” assigned to the containers in the different sterilizer loads shall be the same “Batch Number” as is assigned to the homogenous bulk solution, provided the samples taken from all the sterilizer loads pass the sterility test, and are kept separate from one another until the report of the sterility test is available.
EXPLANATION :--- For the purpose of chemical and other tests, representative samples from all containers filled from the homogenous bulk solution should be taken.
(6) In the case of parenteral and other sterile products filled aseptically, a “Batch Number” shall be assigned to all containers filled from one homogenous mix during one filling operation, the filling operation being completed in a period of not more than a day and during which no schedule change in the filling assembly is made.
When containers are filled from one homogenous mix, in a number of filling operations, the “Batch Number” assigned to the containers filled in individual filling operations shall be the same “Batch Number” as is assigned to the homogenous mix, provided the samples taken from all the different filling operations pass the sterility tests, and are kept separate from one another until the report of the sterility test is available.
EXPLANATION : --- For the purpose of chemical and other tests, representative samples from all containers filled from the homogenous mix should be taken.
(7) In the case of medicinal gases produced by a continuous process of operation a week’s production from one tank load shall be considered as a Batch :
(vi) Every drug manufactured in India shall bear on its label the number of the licence under which the drug is manufactured, the figure representing the manufacturing licence number being preceded by the words “Manufcaturing Licence Number” or “Mfg. Lic. No.” or “M.L.”;
(vii) Drugs specified in Schedule P and their preparations including combinations with other drugs shall bear on their labels the date of manufacture, and the date of expiry of potency, and the period between the date of manufacture and the date of expiry
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shall not exceed that laid down in the said Schedule 1[under the conditions of storage specified therein. 2[Drugs and their preparations not included in Schedule P], shall bear on their labels the date of their manufacture and also the date of their expiry which shall not exceed sixty months from the date of manufacture]
Provided that this period may be extended by the Licensing Authority specified in clause (b) of rule 21 in respect of any specified drug if satisfactory evidence is produced by the manufacturer to justify such an extension.
(viii)Drugs specified in Schedule C (1) and their preparations including combinations with other drugs shall bear on the labels (a) the date of manufacture, (b) date of expiry of potency fixed by the manufacturer, and (c) where such drugs are imported, also the number of licence under which the drug is imported, preceded by the words “Import Licence”
1[Provided that drugs in bulk form included in Schedule C(I) which are not ready for use and not included in Schedule P need not bear on the label the date of expiry of potency;]
2 [Provided further] that no reference shall be made to any other licence number granted by any authority outside India on any label or container or in any covering in which the container is packed or in any other matter or advertisement enclosed herewith;
(ix) Every drug intended for distribution to the medical profession as a free sample shall, while complying with the labelling provisions under clauses (i) to (viii), further bear on the label of the container the words ‘Physician’s Sample—Not to be sold’ which shall be overprinted.
3[(x) If any preparation contains not less than 3 per cent by volume of alcohol the quantity of alcohol shall be stated in terms of the average percentage by volume of absolute alcohol in the finished products.]
4[(xi)In addition to the other particulars which are required to be printed or written under these rules, the label of innermost container of the following categories of drugs and every other covering in which the container is packed shall bear a conspicuous red vertical line on the left side running throughout the body of the label which should not be less than 1mm in width and without disturbing the other conditions printed
____________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 487(E) dt 2.7.1984 & Subs. by G.O.I. Notification No.GSR 813(E) dt 27.7.1998.
2 Ins. by G.O.I. Notification No. GSR 487(E) dt 2.7.1984 3 Ins. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982 4 Ins. by G.O.I. Notification No. GSR 597(E) dt 17.6.1992.
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on the label under these rules, namely:- Narcotic analgesics, hypnotics, sedatives, tranquillisers, corticosteroids, hormones, hypoglycemics, antimicrobials, antiepileptics, antidepressants, anticoagulants, anti- cancer drugs and all other drugs falling under Schedules ‘G’, ‘H’, and ‘X’ whether covered or not in the above list:
Provided that the provisions of this clause shall not apply to.- (a) preparations intended for animal treatment; (b) preparations intended for external use; (c) Ophthalmic preparations and ear drops; and (d) Sterile preparations such as sutures, surgical dressings and preparations intended
for parenteral use.]
(2) (i) The particulars to be printed or written on the label of a mechanical contraceptive shall be as specified in Schedule R.
(ii) The following particulars, in addition to those specified under sub-rule (i) shall be either printed or written in indelible ink and shall appear in a conspicuous manner on the label of the innermost container and on every other covering in which the container of a contraceptive, other than a mechanical contraceptive, is packed, namely :---
(a) the date of manufacture; (b) the date upto which the contraceptive is expected to retain its properties; (c) the storage conditions necessary for preserving the properties of the
contraceptive upto the date indicated in sub-clause (b) :
Provided that for oral contraceptives it shall be sufficient to display on the label of the container the date of manufacture only.
(3) (i) The particulars prescribed in sub-rule (1) shall be printed or written in indelible ink either on the label borne by a container of vaccine lymph or on a label or wrapper affixed to any package in which the container is issued for sale. The said particulars shall be indelibly marked on the sealed container of surgical ligature or suture or printed or written in indelible ink on a label enclosed therein.
(ii) Nothing in these rules shall be deemed to require the labelling of any transparent cover or of any wrapper, case or other covering used solely for the purpose of packing, transport or delivery.
(4) Where be any provision of these rules any particulars are required to be displayed on a label on the container, such particulars may, instead of being displayed on a label, be etched, painted or otherwise indelibly marked on the container :
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Provided that, except where otherwise provided in these rules, the name of the drug or any distinctive letters intended to refer to the drug shall not be etched, painted or otherwise indelibly marked on any glass container other than ampoules.
Explanation :--- For the purpose of this rule, the date of expiry shall be in terms of month and year and it shall mean that the drug is recommended till the last day of the month. The date of expiry shall be preceded by the words ‘Expiry date’.
97. Labelling of medicines--- 1[(1) The container of a medicine for internal use shall—
(a) if it contains a substance specified in Schedule G, be labeled with the words ‘Caution: it is dangerous to take this preparation except under medical supervision’ – conspicuously printed and surrounded by a line within which there shall be no other words;
(b) if it contains a substance specified in Schedule H be labelled with the symbol Rx and conspicuously displayed on the left top corner of the label and be also labelled with the following words:
Schedule H drug- Warning : To be sold by retail on the prescription of a Registered Medical Practitioner only.’,
(c) If it contains a substance specified in Schedule H, and comes within the purview of the [Narcotic Drugs and Psychotropic Substances Act, 1985 (61 of 1985)] be labeled with the symbol NRx which shall be in red and conspicuously displayed on the left top corner of the label, and be also labeled with the following words:
Schedule H drug -“Warning:-- To be sold by retail on the prescription of a Registered Medical Practitioner only.”
(d) If it contains a substance specified in Schedule X, be labeled with the symbol XRx which shall be in red conspicuously displayed on the left top corner of the label and be also labeled with the words : -
Schedule X drug -“Warning:-- To be sold by retail on the prescription of a Registered Medical Practitioner only.”
(2) The container of a embrocation, liniment, lotion, 2[ointment, antiseptic cream,] liquid antiseptic or other liquid medicine for external application shall be labeled with the word in capital ‘For External use only.’]] _____________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 2 Subs. by G.O.I. Notification No. GSR 850(E) dt 7.12.1984.
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1(3)The container of a medicine made up ready only for treatment of an animal shall be labelled conspicuously with the words ‘Not for human use; for animal treatment only’ and shall bear a symbol depicting the head of a domestic animal.
(4) [ * * *] Omitted as per G.O.I. Notification No. 462 (E) dt 22.6.1982..
2[(4) The container of a medicine prepared for treatment of human ailments shall if the medicine contains industrial methylated spirit, indicate this fact on the label and be labelled with the words : “For External Use only”.
(5) Substances specified in Schedule X in bulk form shall bear a label wherein they symbol as specified in sub-rule (1) shall be given conspicuously in red letters.]
[* * * Rules 98, 99, 100 and 101 deleted as per G.O.I. Notification No. GSR 462(E) dt 22.6.1982].
3[102. Non-Sterile Surgical Ligature and Suture.- Every container of, and wrapper enclosing surgical ligature or suture other than a ligature or suture offered or intended to be offered for sale as sterile, shall bear a label on which are printed or written in a conspicuous manner in indelible red ink the words “Non-sterile surgical ligature (suture) – not be used for operations upon the human body unless efficiently sterilized”.
103[* * * (1) Omitted as per G.O.I. Notification No. F.1-16/57-D dt 6.6.1957.]
(2) The name and address of the manufacturer shall be printed on the label of the container of a patent or proprietary medicine.
4(3)The true formula or list of the ingredients shall be printed or written in indelible ink on the outer label of every package containing patent or proprietary medicine.
5[104 Use of letter I.P. etc.-The letters ‘I.P’. and recognized abbreviations of pharmacopoeias and official compendia of drug standards prescribed under these rules shall be entered on the label of the drug only for the purpose of indicating that the drug is in accordance with standards set out in the Indian Pharmacopoeia or in any such pharmacopoeia or official compendium of drug standards recognized under the Rules.] _____________________________________________________________________________ 1Amended by G.O.I. Notification No. F.1-6/62-D dt 2.7.1969 2Sub Rule (5) re-numbered as No.(4) & new sub-rule (5) ins. as per G.O.I. Notification 462(E) dt 22.6.1982. 3Amended by G.O.I. Notification No. F.1-3/51-DS dt 15.10.1954. 4Amended as per G.O.I. Notification No. F.1-16/57-D dt 6.6.1957
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1[104-A. Prohibition against altering inscriptions on containers, labels or wrappers of drug. - No person shall alter, obliterate or deface any inscription or mark made or recorded by the manufacturer on the container, label or wrapper of any drug.
Provided that nothing in this rule shall apply to any alteration, any inscription or mark made on the container, label or wrapper of any drug at the instance or direction or with the permission of the Licensing Authority.]
2[105. Packing of drugs.— (1) The pack sizes of drugs meant for retail sale shall be as prescribed in Schedule P-1 to these rules.
(2) The pack sizes of drugs not covered by the Schedule P-1 shall be as given below: Unless specified otherwise in Schedule P-1, (i) The pack sizes for Tablets/Capsules shall be-
Where the number of Tablets (coated or uncoated)/Capsules (hard or soft gelatin) is less than 10, such packing shall be made by the integral number. For numbers above 10, the pack size of Tablets/Capsules shall contain multiples of 5.
(ii) The pack sizes for liquid Oral preparations shall be 30ml (paediatric only) 60 ml/100 ml/200 ml/450 ml.
(iii)The pack sizes for Paediatric Oral Drops shall be 5 ml/10 ml/15 ml. (iv)The pack sizes for Eye/Ear/Nasal drops shall be 3 ml/5 ml/10 ml. (v) The pack size for Eye Ointment shall be 3 gm/5 gm/ 10 gm.
Provided that the provisions of the pack sizes covered under this rule shall not apply to:
1. Pack sizes or dosage forms not covered by the foregoing provisions of this rule.
2. The imported formulations in finished form. 3. Preparations intended for Veterinary use. 4. Preparations intended for Export. 5. Vitamins/Tonics/Cough Preparations/Antacids/Laxatives in Liquid Oral
forms, Unit dose (including applicaps). 6. Pack sizes of dosage form meant for retail sale to Hospitals, Registered
Medic al practitioners, Nursing Homes. 7. Physician’s Samples. 8. Pack sizes of large volume intravenous fluids.
Provided also that pack sizes of any of the new drug as and when approved by the Licensing Authority appointed under Rule 21 and if not covered under this rule, shall be examined for the purpose of approval with the specific justification by the said Licensing Authority.]
3[Provided further that Oxytocin injection meant for sale shall be in single unit blister pack only.] _______________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 1242(E) dt 17.9.1979 2Ins. by G.O.I.Notification No. GSR 796(E) dt 1.10.1992. 3Ins. by G.O.I. Notification No. GSR 242(E) dt 3.4.2001.
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1[105-A. Packings of drugs specified in Schedule X.- The drugs specified in Schedule X shall be marketed in packings not exceeding-
(i) 100 unit doses in the case of tablets/capsules. (ii) 300ml in the case of oral liquid preparations. (iii)And 5 ml in the case of injections.
Provided that nothing in this rule shall apply to packing meant for use of a hospital or a dispensary subject to the conditions that -
(i) such supplied are made by the manufacturers or distributors direct to the hospital/dispensaries; and
(ii) hospital packs shall not be supplied to a retain dealer or to a Registered Medical Practitioner.]
2[106. Diseases which a drug may not purport to prevent or cure. —(1) No drug may purport or claim to prevent or cure or may convey to the intending user thereof any idea that it may prevent or cure one or more of the diseases or ailments specified in Schedule J.
(2) No drug may purport or claim to procure or assist to procure, or may convey to the intending user thereof any idea that it may procure or assist to procure, miscarriage in women.
[ * * * Omitted as per G.O.I. Notification No. GSR 462(E) dt 22.6.1982.]
3[PART IX-A
LABELLING AND PACKING OR HOMOEOPATHIC MEDICINES
106-A. Manner of labelling of Homoeopathic medicines.—(A) The following particulars shall be either printed or written in indelible ink and shall appear in a conspicuous manner on the label of the innermost container of any Homoeopathic medicine and on every other covering in which the container is packed—
(i) The words ‘Homoeopathic medicine’,
(ii) The name of the medicine— 4[(a) For drugs included in the Homoeopathic Pharmacopoeias of India or
the United States of America or the United Kingdom, or the German Homoeopathic Pharmacopoeia, the name specified in that Pharmacopoeia.]
(b) For other drugs, the name descriptive of the true nature of the drug.
_______________________________________________________________________ 1Ins.by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 2 Amended by G.O.I. Notification No. F. 1-16/52-DC, dated 22-6-1954. 3.Ins.by G.O.I. Notification No. F. 1-63/61-D, dated 17.7.1963. 4Subs. by G.O.I. Notification No. GSR 680(E) dt 5.12.1980.
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(iii) The potency of the Homoeopathic medicine—For this purpose the potency shall be expressed either in decimal, centesimal or millisimal systems.
1[(iii-A) In case of Homoeopathic medicine containing two or more ingredients the name of each ingredient together with its potency and proportion expressed in metric system shall be stated on the label.]
2(iv) Name and address of the manufacturer when sold in original containers of the manufacturer. In case a Homoeopathic medicine is sold in a container other than that of the manufacturer—the name and address of the seller.
(v) In case the Homoeopathic medicine contains alcohol, the alcohol content in percentage by volume in terms of ethyl alcohol shall be stated on the label.
3 [Provided that in case that the total quantity of the pharmacopoeial Homoeopathic medicine in the container is 30 milliliter or less, it will not be necessary to state the content of alcohol in the label.]
(B) In addition to the above particulars the labels of a Homoeopathic mother tincture shall display the following particulars: --
(i) a distinctive batch number, that is to say, the number by reference to which details of manufacture of the particular batch from which the substance in the container is taken are recorded and are available for inspection, the figures representing the batch number being preceded by the words “Batch No.” or “Batch” or “Lot Number” or “Lot No.” or “Lot” or any distinguishing prefix.
(ii) Manufacturing licence number, the number being preceded by the words “Manufacturing Licence Number” or “Mfg. Lic. No.” or “M.L.”.
4Explanation :-- This clause shall not apply to a Homoeopathic mother tincture manufactured outside India.
(C) No Homoeopathic medicine containing a single ingredient shall bear a proprietary name on its label.
________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 466(E) dt 17.5.1994. 2 Amended by G.O.I. Notification No. F.1-59/68-D dated 19-11-1969. 3 Subs. by G.O.I. Notification No. GSR 108(E) dt 22.2.1994. 4 Ins. by G.O.I. Notification S.O. No. 2139 dated 12-8-1972.
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1[106-B. Prohibition of quantity and percentage. - No Homoeopathic medicine containing more than 12% alcohol v/v (Ethyl alcohol) shall be packed and sold in packing or bottles of more than 30 millilitres, except that it may be sold to hospital/dispensaries in packings or bottles of not more than 100 millilitres.]
PART X—SPECIAL PROVISIONS RELATING TO BIOLOGICAL AND OTHER SPECIAL PRODUCTS
2107. Name of substance.—If any substance specified in Schedule C is advertised or sold as a proprietary medicine or is contained in a medicine so advertised or sold, the proper name of the substance shall appear on the label in the manner prescribed in this Part.
3Explanation :-- For the purpose of this rule the expression “Proper name” means the proper name stated in Schedule F or if no such name is stated, the name descriptive of the true nature and origin of the substance. Provided that in the case of veterinary biological product the expression “proper name” means the proper name stated in Schedule F (1) or if no such name is stated, the name or synonym given in the current edition for the time being of the 5[British Pharmacopoea (Veterinary)] , or, if no such name is stated either in Schedule F (1) or the 5[British Pharmacopoea (Veterinary)], the name descriptive of the true nature and origin of the substance approved by the Licensing Authority.
108. Container.—4(1) No substance specified in Schedule C shall be sold or offered for sale unless it has been sealed in a previously sterilized container made of glass or any other suitable material approved for the purpose by the Licensing Authority appointed under rule 21, in such manner as may, in the opinion of the Licensing Authority, suffice to preclude the access of bacteria.
Provided that it shall not be necessary to use a previously sterilized container if the filled and sealed container is to be sterilized after the sealing and such sterilizing procedure would render the product sterile. However, the Licensing Authority may, for any special reasons, direct the licensee to pre-sterile such containers.
(2) When any such substance is issued in liquid form in containers which are sealed in such a manner that portions of the contents can be withdrawn for use on different occasions, the liquid shall contain a sufficient proportion of some antiseptic to prevent the growth of any organisms which may be accidentally introduced in the process of removing a portion of the contents of the container.
_______________________________________________________________________ 1 Ins, by G.O.I. Notification No. GSR 108(E) dt 22.2.1994 w.e.f. 22.6.1994. 2Amended by G.O.I. Notification No. F. 1-5/47-D, dated 25-11-1949. 3Amended by G.O.I. Notification No. F. 1-6/62-D, dated 2-7-69. 4Amended by G.O.I. Notification G.S.R. No. 245 dated 21-2-1976.. Subs by G.O.I. Notification No. G.S.R.647(E) dt 28.10.1998
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Provided that nothing in this sub-rule shall apply to a penicillin suspension in oil and water.
1(3) The container shall comply with such further requirements, if any, as are specified in Schedule F or Schedule F (1) as the case may be, in that behalf.
1(4) The Licensing Authority may in the case of any particular preparation of any such substance dispense with any such substance dispense with any of the requirements of this Rule or Schedule F or Schedule F (1) as the case may be, and may make such additional requirements, as having regard to the nature of the preparation, they may deem necessary.
2109-Labelling-(1) The following particulars and such further particulars, if any, as are specified in Schedule F or Schedule F (1), as the case may be, shall be printed or written in indelible ink on the label of every phial, ampoule or other container of a substance specified in Schedule C and on every other covering in which such phial, ampoule or container is packed—
(a) where a drug is imported, the number of licence under which it is imported, preceded by the words ‘Import Licence’:
Provided that no reference shall be made to any other import licence number granted by any authority outside India on any label or container or in any covering in which the container is packed or in any other matter of advertisement enclosed therein.
(b) Where a test for potency in units is required by these rules, a statement of the potency in units defined in terms of relation to the standard preparation specified in Schedule F or F (1), as the case may be :
Provided that this clause shall not apply in the case of vaccine lymph.
(c) where a test for potency or maximum toxicity is required the date upto which the substance if kept under suitable conditions may be expected to retain a potency not less than stated on the label of the container or not to acquire a toxicity greater than that permitted by the test, as the case may be. The date of expiry shall be in terms of month and year and it shall mean that the drug is recommended for use till the last day of the month. The date of expiry shall be preceded by the words ‘Expiry date’ :
Provided that nothing in these rules shall be deemed to require the labelling of any transparent cover or any wrapper, case or other covering used solely for the purpose of packing, transport or delivery.
1Amended by G.O.I. Notification No. F.1-6/62-D dated 2-7-1969. 2Amended by G.O.I. Notification No. G.S.R.19 dated 7/1/1978.
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(2) The particulars prescribed in clause (a) of the preceding sub-rule shall be printed or written in indelible ink either on the label borne by a container of vaccine lymph or on a label or wrapper affixed to any package in which the container is issued for sale. The said particulars shall be indelibly marked on the sealed container of surgical ligature or suture or printed or written in indelible ink on a label enclosed therein.
(3) The following particulars, and such further particulars and such further particulars, if any, as are specified in Schedule F or schedule F (1), as the case may be, shall be printed or written in indelible ink either on the label borne by the container of any substance specified in Schedule C or on a label or wrapper affixed to any package in which any such container is issued for sale, namely :--
(a) the date on which the manufacture of the particular batch from which the substance in the container is taken was completed as defined in Schedule F or Schedule F (1), or if there is no definition in Schedule F or Schedule (1) as hereafter defined in this rule and in the case of vaccine prepared from concentrates, the date of completion of the final products and the bottling for issue;
(b) where an antiseptic substance has been added, the nature and the percentage proportion introduced;
(c) the perception necessary for preserving the properties of the contents up to the date indicated in clause (c) of sub-rule (1).
(4) For the purpose of clause (a) of sub-rule (3), the date on which the manufacture of a batch is completed shall be—
(a) in cases where a test for potency or toxicity is required by these rules or not being so required, is accepted by the Licensing Authority as sufficient for the purpose of fixing the date of completion of manufacture, the date on which the substance was removed from cold storage after having been kept at a temperature not exceeding 5°C continuously for a period not exceeding two years from the time when the last test was completed.
(b) in cases where no such test is required or accepted;
(i) if the substance is a serum obtained from a living animal, the earliest date on which any material contributing to the batch was removed from the animal;
(ii) if the substance was obtained by the growth of organisms or artificial media, the earliest date on which growth was terminated in any of the material contributing to the batch:
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Provided that if a batch of the substance (including all material contributing to this batch) has for a period of not more than three years been kept in cold storage at a temperature not exceeding 5°C continuously from the earliest practicable date after that on which growth was terminated in the material as the case may be, the date of removal from cold storage shall be treated as the date on which the manufacture of the batch is completed.
(c) in all other cases, the date on which the substance is filled in the container.
1[109-A. Labelling of Medical Devices.- The labeling of Medical Devices shall conform to the Indian Standards Specifications laid down from time to time by the Bureau of Indian Standards in addition to any other requirement prescribed under the said rules.]
110. Prohibition of sale of substance after prescribed date—No person shall sell, or exhibit for sale any substance specified in Schedule C after the date recorded on the container, label or wrapper as the date upto which the substance may be expected to retain a potency not less than, or not to acquire a toxicity greater than that required or permitted by the prescribed test as the case may be.
110-A.[ * * * Omitted by G.O.I. Notification No. GSR 1242(E) dt 17.9.1979.
2111.Standards—Every substance specified in Schedule C and C (1) intended for sale shall confirm with the standards of strength, quality and purity specified in these Rules and in Schedule F or F (1), as the case may be, and the tests for determining such conformity shall be applied to samples taken from the final product after every manufacturing process has been completed.
2112. Tests for strength and quality—The tests, if any, required for determining the strength and quality of each of the substances specified in Schedules C and C (1) shall be those set out in Schedule F or Schedule F (1) 3[or as specified]as the case may be.
[* * * Rules 113 and 114 Omitted as per G.O.I. Notification G.S.R. No.663(E) dt 3.7.1992.]
115. Application of tests for sterility—The tests shall be applied —
(a) to samples taken from each batch of the substance before the operation of filling and sealing the containers in which it is to be issues has commenced except preparations, which after being sealed in the containers are to be sterilized by heat, in a manner satisfactory to the Licensing Authority; and
(b) to the contents of sample containers when ready for issue. ____________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 109(E) dt 22.2.1994. 2Amended by G.O.I. Notification No. F.1-6/62-D, dated 2-7-1969.
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[* * * Rules 116, 117 and 118 Omitted as per G.O.I. Notification No. GSR 663(E) dt 3.7.1992.]
119. (1) If at this examination no growth of micro-organisms is found in any tube, the sample may be treated as having passed the test.
(2) If at the examination of a growth of micro-organisms is visible, further samples may be taken and the tests may be repeated on the further samples taken: but no container the contents of which form part of the batch shall be issued until such further samples have passed the test. The process of taking samples from the batch for a test may be repeated twice :
Provided that if the same organism is visible in more than one test the batch shall be treated as not sterile and the material contained in the batch shall not be issued or used as part of a further batch unless and until it has been re-sterilized and has passed the tests.
120. Notwithstanding anything contained in the last preceding Rule in any case where—
(a) a substance is required in an emergency by a registered medical practitioner, but the licensee has no filled containers in stock; or
(b) a substance which in the opinion of the Licensing Authority is so unstable in solution that the delay occasioned by the completing of the sterility test on filled containers would render its issue in active form impossible, the licensee may issue the substance from a batch which has already passed the tests for sterility and freedom from abnormal toxicity, without completing the sterility test on the filled containers, provided that he complies with the following conditions—
(i) the licensee shall before the issue take samples in the required proportion from the containers into which the batch is filled, and after the required inoculation shall examine the tube every day for five days;
(ii) if at any examination any growth is visible in any of the tubes, he shall immediately notify the Licensing Authority;
(iii) he shall keep available for inspection a record of all issues made under this Rule containing such particulars of the circumstances in which the issue is made as the Licensing Authority may require.
1[121. Test for freedom from abnormal toxicity—The test for freedom from abnormal toxicity shall be carried out as per the current edition of Indian Pharmacopoeia in the case of each batch of the serum tested by the licensee or by an institution approved by the licensing authority for the purpose of carrying out the test on its behalf.] _______________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 753(E) dt 4.11.1999.
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1121-A Test for pyrogens—Solution of substances intended for parenteral administration in large volumes (10ml or more at a time) shall be pyrogen-free and tested for pyrogens. If water or any other adequate solvent is supplied along with the substances preparing such solutions, it shall also be pyrogen-free and tested for pyrogens.
122. Substances specified in Schedule C (1)—The following provisions shall apply in the case of a substance specified in Schedule C (1):--
2(a) The container shall comply with the requirements, if any, specified in Schedule F or Schedule F (1), 3[or as specified] as the case may be.
(b) [* * * Deleted as per G.O.I. Notific ation No. GSR 19 dt 7.1.1978].
2(c) The substance shall conform to the standards of strength, quality and purity specified in Schedule F or Schedule F (1) 3[or as specified], as the case may be and the tests for determining the strength, quality and purity of the substance shall be those specified in Schedules F or Schedule F (1) 3[or as specified,] as the case may be.
2(d) The tests for determining the strength, quality and purity of a substance specified in Schedule F or Schedule F (1) 3[or as specified] as the case may be shall be applied to samples taken from the final product after each manufacturing process has been completed.
(e) The substance should be stored in a cool place and away from light.
4[PART XA
IMPORT OF MANUFACTURE OF NEWDRUG FOR CLINICAL TRIALS OR MARKETING
122-A. Application for permission to import new drug.- 5[(1) (a) No new drug shall be imported, except under, and in accordance with, the permission granted by the Licensing Authority as defined in clause (b) of rule 21.
(b) An application for the grant of permission to import a new drug shall be made in Form 44 to the Licensing Authority, accompanied by a fee of fifty thousand rupees.
Provided further that where a subsequent application by the same applicant for that drug, whether in modified dosage form or with new claims, is made, the fee to accompany such application shall be fifteen thousand rupees. ________________________________________________________________________ 1Added under G.O.I. Notification No. F.1-27/56-D, dated 18-12-1956 2Amended by G.O.I.Notification no. F.1-6/62-D, dated 2-7-1969 3Subs. by G.O.I. Notification No. GSR 663(E) dt 3.7.1992. 4 Ins. by G.O.I. Notification No. GSR 944(E) dt 21.9.1988 5Subs. by G.O.I. Notification No. GSR 900(E) dt 12.12.2001.
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Provided further that any application received after one year of the grant of approval for the import and sale of new drug, shall be accompanied a fee of fifteen thousand rupees and such information and data as required by Appendix I or Appendix I-A of Schedule Y, as the case may be].
(2) The importer of a new drug when applying for permission under sub-rule (1), shall submit data as given in Appendix I to Schedule Y including the results of local clinical trials carried out in accordance with the guidelines specified in that Schedule and submit the report of such clinical trials in the format given n appendix II to the said Schedule.
Provided that the requirement of submitting the results of local clinical trials may not be necessary if the drug is of such a nature that the Licensing Authority may, in public interest decide to grant such permission on the basis of data available from other countries.
Provided further that the submission of requirements relating to Animal Toxicology, Reproduction studies, Teratogenic studies, Perinatal studies, Mutagenicity and Carcinogenicity may be modified or relaxed in case of new drugs approved and marketed for several years in other countries if he is satisfied that there is adequate published evidence regarding the safety of the drug, subject to the other provisions of these rules.
1[(3) the Licensing authority, after being satisfied that the drug if permitted to be imported as raw material (bulk drug substance) or as finished formulation shall be effective and safe for use in the country, may issue an import permission in Form 45 and/or Form 45-A, subject to the conditions stated therein.
Provided that the Licensing Authority shall, where the data provided or generated on the drug is inadequate, intimate the applic ant in writing, and the conditions, which shall be satisfied before permission could be considered.]
122-B. Application for approval to manufacture new drug other than the drugs classifiable under Schedules C and C(1).- 1[(1)(a) No new drug shall be manufactured for sale unless it is approved by the Licensing Authority as defined in clause (b) of Rule 21.
(b) An application for the grant of approval to manufacture the new drug and its formulations shall be made in Form 44 to the Licensing Authority as defined in clause (b) of Rule 21 and shall be accompanied by a fee of fifty thousand rupees.
Provided that where the application is for permission to import a new drug (bulk drug substance) and grant of approval to manufacture its formulation/s, the fee to accompany such application shall be fifty thousand rupees only.
_____________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 900(E) dt 12.12.2001
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Provided further that where a subsequent application by same applicant for that drug, whether in modified dosage form or with the new claims, is made, the fee to accompany such subsequent application shall be fifteen thousand rupees.
Provided further also that any application received after one year of the gran t of approval for the manufacture for sale of the new drug, shall be accompanied by a fee of fifteen thousand rupees and such information and data as required by Appendix 1 or Appendix 1-A of Schedule Y, as the case may be.]
(2) The manufacturer of a new drug under sub-rule (1) when applying for approval to the Licensing Authority mentioned in the same sub-rule, shall submit data as given in Appendix 1 to Schedule Y including the results of clinical trials carried out in the country in accordance with the guideline specified in Schedule Y and submit the report of such clinical trials in the same format given in Appendix II to the said Schedule.
1[(2-A) The Licensing authority, as defined in clause (b) of Rule 21 after being satisfied that the drug if approved to be manufactured as raw material (bulk drug substance) or as finished formulation shall be effective and safe for use in the country, shall issue approval in Form 46 and/or Form 46-A, as the case may be, subject to the conditions stated therein.
Provided that the Licensing Authority shall, where the data provided or generated on the drug is inadequate, intimate the applicant in writing, and the conditions, which shall be satisfied before permission could be considered.]
(3) When applying for approval to manufacture a new drug under sub-rule (1) or its preparations, to the State Licensing Authority, an applicant shall produce along with his application, evidence that the drug for the manufacture of which application is made has already been approved by the Licensing Authority mentioned in Rule 21.
Provided that the requirement of submitting the results of local clinical trials may not be necessary if the drug is of such nature that the Licensing Authority may, in public interest decide to grant such permission on the basis of data available from other countries.
Provided further that the submission of requirements relating to Animal Toxicology, Reproduction studies, Teratogenic studies, Perinatal studies, Mutagenicity and Carnicogenicity may be modified or relaxed in case of new drugs approved and marketed for several years in other countries if he is satisfied that there is adequate polished evidence regarding the safety of the drug, subject to the other provisions of these rules.
122-C [*** Deleted as per G.O.I. Notification No. GSR 900(E) dt 12.12.2001.]
1[122-D. Permission to import or manufacture fixed dose combination.- (1) An application for permission to import or manufacture fixed dose combination of two or ore ________________________________________________________________________ 1 Ins./Subs. by G.O.I. Notification No. GSR 900(E) dt 12.12.2001
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drugs as defined in clause (c) of Rule 122-E shall be made to the Licensing Authority as defined in clause (b) of Rule 21 in Form 44, accompanied by a fee of fifteen thousand rupees and shall be accompanied by such information and data as is required in Appendix VI of Schedule Y.
(2) The Licensing Authority after being satisfied that the fixed dose combination if approved to be imported or manufactured as finished formulation shall be effective and safe for use in the country, shall issue permission in Form 45 or Form 46, as the case may be, subject to the conditions stated therein.
Provided that the Licensing authority shall where the data provided or generated on the fixed dose combination is inadequate, intimate the applicant in writing, and the conditions which shall be satisfied before grant of approval/permission could be considered.
122-DA. Application for permission to conduct clinical trials for New Drug/Investigational New Drug.- (1) No clinical trial for a new drug, whether for clinical investigation or any clinical experiment by any institution, shall be conducted except under, and in accordance with, the permission, in writing, of the Licensing Authority defined in clause (b) of Rule 21.
(2) An application for grant of permission to conduct.-
(a) human clinical trials (Phase-I) on a new drug shall be made to the Licensing Authority in Form 44 accompanied by a fee of fifty thousand rupees and such information and data as required under Schedule Y.
(b) exploratory clinical trials (Phase-II) on a new drug shall be made on the basis of data emerging from Phase I trial, accompanied by a fee of twenty- five thousand rupees;
(c) confirmatory clinical trials (Phase-III) on a new drug shall be made on the basis of the data emerging from Phase-II and where necessary, data emerging from Phase-I also, and shall be accompanied by a fee of twenty- five thousand rupees,
Provided that no separate fee shall be required to be paid along with application for import/manufacture of a new drug based on successful completion of phases clinical trials by the applicant.
Provided further that no fee shall be required to be paid along with the application by Central Government or State Government Institutes involved in clinical research for conducting trials for academic or research purposes.
(3) The Licensing Authority after being satisfied with the clinical trials, shall grant permission in Form 45 or Form 45-A or Form 46 or Form 46-A, as the case may be, subject to the conditions stated therein.
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Provided that the Licensing Authority shall, where the data provided on the clinical trials is inadequate, intimate the applicant in writing, within six months from the date of such intimation or such extended period, not exceeding a further period of six months, as the Licensing Authority may, for reasons to be recorded in writing, permit, intimating the conditions which shall be satisfied before permission could be considered.
Explanation.- For the purpose of these rules Investigational New Drug means a new chemical entity or a product having therapeutic indication but which have never been earlier tested on human beings.
122-DB. Suspension or cancellation of Permission/Approval. - If the improper or manufacturer under this Part fails to comply with any of the conditions of the permission or approval, the Licensing Authority may, after giving an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefore, suspend or cancel it.
122-DC. Appeal.- Any person aggrieved by an order passed by the Licensing Authority under this Part, may within sixty days from the date of such order, appeal to the Central Government, and the Central Government may, after such enquiry into the matter as is considered necessary, pass such an order in relation thereto as it thinks fit.]
122-E. Definition of new drug.- For the purpose of this part, new drug shall mean and include.-
1[(a) A drug, as defined in the Act including bulk drug substance which has not been used in the country to any significant extent under the conditions prescribed, recommended or suggested in the labeling thereof and has not been recognized as effec tive and safe by the licensing authority mentioned under Rule 21 for the proposed claims.
Provided that the limited use, if any, has been with the permission of the licensing authority.]
(b) A new drug already approved by the Licensing Authority mentioned in Rule 21 for certain claims, which is now proposed to be marketed with modified or new claims, namely, indications, dosage, dosage form (including sustained release dosage form) and route of administration.
(c) A fixed dose combination of two or more drugs, individually approved earlier for certain claims, which are now proposed to be combined for the first time in a fixed ratio, or if the ratio of ingredients in an already marketed combination is proposed to be changed, with certain claims, viz. indic ations, dosage, dosage form (including sustained release dosage form) and route of administration. (See items (b) and (c) of Appendix VI to Schedule Y.)
________________________________________________________________________ 1Subs. by G.O.I. NotificationNo. GSR 591(E) dt 17.8.1999.
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Explanation.- For the purpose of this rule. - (i) all vaccines shall be new drugs unless certified otherwise by the Licensing
Authority under Rule 21; (ii) a new drug shall continue to be considered as new drug for a period of four
years from the date of its first approval or its inclusion in the Indian Pharmacopoeia, whichever is earlier.]
1[PART XB
REQUIREMENTS FOR THE COLLECTION, STORAGE, PROCESSING AND DISTRIBUTION OF WHOLE HUMANBLOOD,
HUMAN BLOOD COMPONENTS BY BLOOD BANKS AND MANUFACTURE OF BLOOD PRODUCTS.
2[122-EA. Definitions.- (1) In this Part and in the Forms contained in Schedule A and in Part XII-B and Part XII-C of Schedule F, unless there is anything repugnant in the subject or context. -
(a) “apheresis” means the process by which blood drawn from a donor, after separating plasma or platelets or leucocytes, is re-transfused simultaneously into the said donor;
(b) “autologous blood” means the blood drawn from the patient for re- transfusion into himself later on;
(c) ‘blood” means a place or organization or unit or institution or other arrangements made by such organization, unit or institution for carrying out all or any of the operations for collection, apheresis, storage, processing and distribution of blood drawn from donors and/or for preparation, storage and distribution of blood components.
(d) “blood bank” means a place or organization or unit or institution or other arrangements made by such organization, unit or institution for carrying out all or any of the operations for collection, apheresis, storage, processing and distribution of blood drawn from donors and/or for preparation, storage and distribution of blood components;
(e) “blood component” means a drug prepared, obtained, derived or separated from a unit of blood drawn from a donor;
(f) “blood product” means a drug manufactured or obtained from pooled plasma of blood by fractionation, drawn from donors;
________________________________________________________________________ 1Ins. By G.O.I. Notification No. GSR 28(E) dtd 22.1.1993. 2Ins. by G.O.I. Notification No.245(E) dt 5.4.1999.
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(g) “donor” means a person who voluntarily donates blood after he has been declared fit after a medical examination, for donating blood, on fulfilling the criteria given hereinafter, without accepting in return any consideration
Explanation.- For the purposes of this clause, benefits or incentives like pins, plaques, badges, medals, commendation certificates, time-off from work, membership of blood assurance programme, gifts of little or intrinsic monetary value shall not be construed as consideration.
(h) “leucapheresis” means the process by which the blood drawn from a donor, after leucocyte concentrates have been separated is re-transfused simultaneously into the said donor,
(i) “plasmapheresis” means the process by which the blood drawn from a donor, after plasma has been separated, is re-transfused during the same sitting into the said donor;
(j) “plateletpheresis” means the process by which the blood drawn from a donor, after platelet concentrates have been separated, is re-transfused simultaneously into the said donor.
(k) “professional donor” means a person who donates blood for a valuable consideration, in cash or kind, for any source, on behalf of the recipient- patient and includes a paid donor or a commercial donor,
(l) “replacement donor” means a donor who is a family friend or a relative of the patient-recipient.]
122-F. Form of application for licence for operation of Blood Bank/processing of whole human blood for components/manufacture of blood products for sale or distribution.- (1) Application for the grant and/or renewal of licence for the operation of a Blood Bank/processing of human blood for components/manufacture of blood products shall be made to the Licensing Authority appointed under Part VII in 1[Form 27-C or Form 27-E,as the case may be], and shall be accompanied by 2[licence fee of rupees six thousand and an inspection fee of rupees one thousand and five hundred for every inspection thereof or for the purpose of renewal of licence].
Provided that if the applicant applies for renewal of licence after its expiry but within six months of such expiry the fee payable for the renewal of the licence 2[shall be rupees six thousand and inspection fee of rupees one thousand five hundred plus an additional fee at the rate of rupees one thousand per month or a part thereof in addition to the inspection fee].
Provided further that a licensee holding a licence in 1[Form 28-C or Form 28-E,as the case may be,] for operation of Blood Bank/processing of whole human blood for _____________________________________________________________________ 1 Ins. by G.O.I. Notification No.245(E) dt 5.4.1999. 2 Subs, by G.O.I. Notification No. GSR 601(E) dt 24.8.2001.
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components/manufacture of blood products shall apply for grant of licence under sub- rule(1) before the expiry of the said licence on 1[Form 27-C or Form 28E, as the case may be,] and he shall continue to operate the same till the orders on his application are communicated to him.
2[Explanation.- For the purpose of this rule, “Blood Bank” means a place or organizational unit or an institution or other arrangement made by such organizational unit or institution for carrying our all or any of the operations of manufacture of human blood components, or blood products or whole human blood for its collection, storage, processing, distribution from selected human donors.]
(2) A fee of 3[rupees one thousand] shall be paid for a duplicate copy of a licence issued under this rule, if the original is defaced, damaged or lost.
(3) Application by a licensee to manufacture additional drugs listed in the application shall be accompanied by a 3[fee of rupees three hundred] for each drug listed in the applicat ion.
(4) On receipt of the application for the grant or renewal of such licence, the Licensing Authority shall, -
(i) verify the statements made in the application form (ii) cause the manufacturing the testing establishment to be inspected in
accordance with the provision of Rule 122-I and (iii) in case the application is for renewal of licence, call for information of past
performance of the licence. (5) If the Licensing Authority is satisfied that the applicant is in a position to fulfil the
requirements laid down in the rules, he shall prepare a report to that effect and forward it 2[along with the application and the licence (in triplicate) to be granted or renewed, duly completed] to the Central Licence Approving Authority.
Provided that if the Licensing Authority is of the opinion that the applicant is not in a position to fulfil the requirements laid down in these rules, he may, by order, for reasons to be recorded in writing, refuse to grant or renew the licence, as the case may be.
(6) If, on receipt of the application and report of the Licensing Authority referred to in sub-rule (5) and after taking such measures including inspection of the premises, by the Inspector, appointed by the Central Government under Section 21 of the Act, and/or along with the Expert in the field concerned if deemed necessary, the Central Licence approving authority is satisfied that the applicant is in a position to fulfil the requirements laid down in these rules, he may grant or renew the licence, as the case may be.
_______________________________________________________________________ 1Ins. by G.O.I. Notification No.245(E) dt 5.4.1999. 2Subs. by G.O.I. Notification No. GSR 89(E) dt 14.2.1996. 3Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001
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Provided that if the Central Licence approving Authority is of the opinion that the applicant is not in a position to fulfil the requirements laid down in these rules he may, notwithstanding the report of the Licensing Authority, by order, for reasons to be recorded in writing, reject the application for grant or renewal of licence, as the case may be, and shall supply the applicant with a copy of the inspection report.
122-G. Form of Licence for the operation of a Blood Bank/processing of whole human blood for components and manufacture of blood products and the conditions for the grant or renewal of such licence. - A licence for the operation of a Blood Bank or for processing whole human blood for components and manufacture of blood products shall be issued in 1[Form 28-C or Form 28-E or Form 26-G or Form 26-I, as the case may be]. Before a licence in 1[Form 28-C or Form 28-E or Form 26-G or Form 26-I, as the case may be] is granted or renewed the following conditions shall be complied with by the applicant:-
1[(i) The operation of Blood Bank and/or processing of whole human blood for components shall be conducted under the active direction and personal supervision of competent technical staff consisting of at least one person who is whole-time employee and who is Medical Officer, and possessing-
(a) Postgraduate degree in Medicine - M.D (Pathology/Transfusion Medicines); or
(b) Degree in Medicine (M.B.B.S.) with Diploma in Pathology or Transfusion Medicines having adequate knowledge in blood group serology, blood group methodology and medical principles involved in the procurement of blood and/or preparation of its components; or
(c) Degree in Medicine (M.B.B.S.) having experience in Blood Bank for one year during regular service and also has adequate knowledge and experience in blood group serology, blood group methodology and medical principles involved in the procurement of blood and/or preparation of its components.
the degree or diploma being from a University recognized by the Central Government.
Explanation.- For the purposes of this conditions, the experience in Blood Bank for one year shall not apply in the case of persons who are approved by the Licensing Authority and/or Central Licence Approving Authority prior to the commencement of the Drugs and Cosmetics (Second Amendment) Rules, 1999].
(ii) The applicant shall provide adequate space, plant and equipment for any or all the operations of blood collection or blood processing. The space, plant and equipment required for various operation is given in Schedule ‘F’, Part XII-B and/or XII-C.
________________________________________________________________________ 1Ins. by G.O.I. Notification No.245(E) dt 5.4.1999.
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(iii) The applicant shall provide and maintain adequate technical staff as specified in Schedule F, Part XII-B and/or XII-C.
(iv) The applicant shall provide adequate arrangements for storage of whole human blood, human blood components and blood products.
(v) The applicant shall furnish to the Licensing Authority, if required to do so, data on the stability of whole human blood, its components or blood products which are likely to deteriorate, for fixing the date of expiry which shall be printed on the labels of such products on the basis of the data so furnished.
122-H. Duration of licence.- An original licence in 1[Form 28-C or Form 28-E or a renewed licence in Form 26-G or Form 26-I] unless sooner suspended or cancelled shall be 2[valid for a period of five years on and from the date on which] it is granted or renewed.
122-I. Inspection before grant or renewal of licence for operation of Blood Bank, processing of whole human blood for components and manufacture of blood products.- Before a licence in 1[Form 28-C or Form 28-E is granted or a renewal of licence inform 26-G or Form 26-I is made, as the case may be,] the Licensing Authority or the Central Licence Approving authority, as the case may be, shall cause the establishment in which Blood Bank is proposed to be operated/whole human blood for components is processed/ blood products are manufactured to be inspected by one or more Inspectors, appointed under the Act and/or along with the Expert in the field concerned. The Inspector or Inspectors shall examine all portions of the premises and appliance/equipments and inspect the process of manufacture intend to be employed or being employed along with the means to be employed or being employed for operation of blood bank/processing of whole human blood for components/manufacture of blood products together with their testing facilities and also enquire into the professional qualification of the expert staff and other technical staff to be employed.
122-J. Report by Inspector. - The Inspector or Inspectors shall forward a detailed descriptive report giving his findings on each aspect of inspection along with his recommendation in accordance with the provisions of Rule 122-I to the Licensing Authority or to the Central Licence Approving Authority.
122-K. Further application after rejection .- If within a period of six months from the rejection of application of a licence the applicant informs the Licensing Authority that the conditions laid down have been satisfied and deposits an inspection 2[fee of rupees two hundred and fifty] the Licensing Authority may, if after causing further inspection to be made is satisfied that the conditions for the 1[grant or renewal of a licence have been complied with, shall grant or renew the licence in Form 28-C or Form 28-E. _______________________________________________________________________ 1Ins. by G.O.I. Notification No.245(E) dt 5.4.1999 2Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001
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Provided that in the case of a drug notified by the Central Government under rule 68- A, the application, together with the inspection report and the Form of licence (in triplicate to be granted or renewed), duly completed shall be sent, to the Central Licence approving Authority, who may approve the same and return it to the Licensing Authority for issue of the licence.]
122-L. Delegation of powers by the Central Licence Approving Authority.- The Central Licence Approving Authority may, with the approval of the Central Government, by notification delegate his powers of signing licences and any other power under rules to persons under his control having same qualifications as prescribed for Controlling Authority under rule 50-A, for such areas and for such period as may be specified.
122-M. Provision for appeal to the State Government by a party whose licence has not been granted or renewed.- Any person who is aggrieved by the order passed by the Licensing Authority or Central Licence Approving Authority, as the case may be, may within thirty days from the date of receipt of such order, appeal to the State Government or Central Government, as the case may be, after such enquiry into the matter as it considers necessary and after giving the said person an opportunity for representing his view in the matter may pass such order in relation thereto as it thinks fit.
122-N. Additional information to be furnished by an applicant for licence or by a licensee to the Licensing Authority. - the applicant for the grant of licence or any person granted a licence under the Part shall, on demand furnish to the Licensing Authority, before the grant of the licence or during the period the licence is in force, as the case may be, documentary evidence in respect of the ownership or occupation, rental or other basis of the premises, specified in the application for licence or in the licence granted, constitution of the firm or any other relevant matter, which may be required for the purpose of verifying the correctness obtaining the licence, as the case may be.
122-O. Cancellation and suspension of licences. - (1) The Licensing Authority or Central Licence Approving Authority may for such licences granted or renewed by him after giving the licensee an opportunity to show cause why such an order should not be passed by an order in writing stating the reason thereof, cancel a licence issued under this part or suspend it for such period as he thinks fit, either wholly or in respect of some of the substances to which it relates 1[or direct the licensee to stop collection, storage, processing, manufacture and distribution of the said substances and 2[thereupon order the destruction of substances and] stocks thereof in the presence of an Inspector], if in his opinion, the licensee has failed to comply with any of the conditions of the licence or with any provision of the Act or Rules thereunder.
(2) A licensee whose licence has been suspended or cancelled may, within three months of the date of the order under sub-rule(1) prefer an appeal against the order to the State Government or Central government, which shall decide the same. _______________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 20(E) dt 11.1.1996. 2Subs. by G.O.I. Notification No. GSR 514(E) dt 5.11.1996.
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122-P. Conditions of licence. - 1[A licence in Form 28-C, Form 28-E, Form 26-G or Form 26-I shall be subject to the special conditions set out in Schedule F, Part XII-B and Part XII-C, as the case may be, which relate to the substance in respect of which the licence is granted or renewed and to the following general conditions, namely:-]
(i) (a) The licensee shall provide and maintain adequate staff, plant and premises for the proper operation of a Blood Bank for processing whole human blood, its components and/or manufacture of blood products.
(b) The licensee shall maintain staff, premises and equipment as specified in Rule 122-G. the licensee shall maintain necessary records and registers as specified in Schedule F, Parts XII-B and XII-C.
(c) The licensee shall test in his own laboratory whole human blood, its components and blood products and maintain records and registers in respect of such tests as specified in Schedule F, Parts XII-B and XII-C. The records and register shall be maintained for a period of five years from the date of manufacture.
(d) The licensee shall maintain/preserve reference sample and supply to collect the Inspector the reference sample of the whole human blood collected by him in an adequate quantity to conduct all the prescribed tests. The licensee shall supply to the Inspector the reference sample for the purpose of testing.
(ii) The licensee shall allow an Inspector appointed under the Act to enter, with or without prior notice, any premises where the activities of the Blood Bank and are being carried out for the processing of Whole Human Blood and/or Blood Products, to inspect the premises and plant and the process of manufacture and the means employed for standardizing and testing the substance.
(iii) The licensee shall allow an Inspector appointed under the Act to inspect all registers and records maintained under these rules and to take samples of the manufactured product and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and rules thereunder have been observed.
(iv) The licensee shall from time to time report to the Licensing Authority any changes in the expert staff responsible for the operation of a Blood Bank/processing of whole human blood for components and/or manufacture of blood products and any material alterations in the premises or plant used for that purpose which have been made since the date of last inspection made on behalf of the Licensing Authority before the grant of the licence.
(v) The licensee shall on request furnish to the Licensing Authority, or Central Licence Approving Authority or to such Authority as the Licensing Authority, or the Central Licence Approving Authority may direct, from any batch unit or drugs as the Licensing Authority or Central Licence Approving Authority may from time to time specify, sample of such quantity as may be considered adequate by such Authority for any examination and, if so required, also furnish full protocols of the test which have been applied.
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(vi) If the Licensing Authority of the Central Licence Approving Authority so directs, the licensee shall not sell or offer for sale any batch/unit in respect of which a sample is, or protocols are furnished under the last preceding sub- paragraph until a certificate authorizing the sales of batch/unit has been issued to him by or on behalf of the Licensing Authority or the Central Licence approving Authority.
(vii) The licensee shall on being informed by the Licensing Authority or the Controlling Authority that any part of any batch/unit of the substance has been found by the Licensing Authority or the Central Licence Approving Authority not to conform with the standards of strength, quality or purity specified in these Rules and on being directed so to do, withdraw, from sales and so far as may in the particular circumstances of the case be practicable recall all issues already made from that batch/unit.
(viii) No drug manufactured under the licence shall be sold unless the precautions necessary for preserving its properties have been observed throughout the period after manufacture. Further no batch/unit manufactured under this licence shall be supplied/distributed to any person without prescription of a Registered Medical Practitioner.
(ix) The licensee shall comply with the provisions of the Act and of these Rules and with such further requirements, if any, as may be specified in any Rules subsequently made under Chapter IV of the Act, provided that where such further requirements are specified in the Rules, these would come in force four months after publication in the Official Gazette.
(x) The licensee shall maintain an Inspection Book in Form 35 to enable an Inspector to record his impression and defects noticed.
(xi) The licensee shall destroy the stock of batch/unit which does not comply with standard tests in such way that it would not spread any disease/infection by way of proper disinfection method.
1[(xii) All bio -medical waste shall be treated, disposed of or destroyed as per the provisions of the Bio -Medical Wastes (Management and Handling) Rules, 1996.
(xii) The licensee shall neither collect blood from any professional donor or paid donor nor shall he prepare blood components and/or manufacture blood products from the blood drawn from such a donor.]
PART XI-EXEMPTION
123. The drugs specified in schedule K shall be exempted from the provisions of Chapter IV of the Act and the Rules made thereunder to the extent and subject to the conditions specified in that Schedule.
_______________________________________________________________ 1Ins. by G.O.I. Notification No.245(E) dt 5.4.1999
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PART XII STANDARDS
1124—Standards of drugs:-- (1) Drugs included in the Indian Pharmacopoeia--
(a) The standards for identity, purity and strength shall be those as may be specified in the edition of the Indian Pharmacopoeia for the time being in force.
(b) In case the standards for identity, purity and strength for drugs are not specified in the edition of the Indian Pharmacopoeia for the time being in force but are specified in the edition of the Indian Pharmacopoeia immediately preceding, the standards for identity, purity and strength shall be those occurring in such immediately preceding edition of the Indian Pharmacopoeia.
(2) For other drugs--
(a) The standards for identity, purity and strength shall be those as may be specified in the edition of the official pharmacopoeia, for the time being in force, of any country to which the drug claims to comply with,
(b) In case the standards for identity, purity and strength for drugs are not specified in the edition of such official pharmacopoeia for the time being in force, but are expected in the edition immediately preceding, the standards for identity, purity and strength shall be those occurring in such immediately preceding edition of such official pharmacopoeia to which the drug claims to comply with.
(c) For drugs for which standards are not included in the edition of the official pharmacopoeia, for the time being in force, of any country or in edition immediately preceding, but included in the official compendia of drug standards, namely, the British Pharmaceutical Codex or the National Formulary of the United States, for the time being in force, to which the drug claims to comply with.
2124A.Standards for veterinary drugs—For drugs intended for veterinary use, the standards shall be those given in the current edition for the time being in force of the 3[British Pharmacopoeia (Veterinary)].
4124-B Standards for patent or proprietary medicines : -- The standards for patent or proprietary medicines shall be those laid down in Schedule V and such medicines shall also comply with the standards laid down in the Second Schedule to the Act. ________________________________________________________________________ 1Amended by G.O.I. Notification No. GSR 19 dt 7.1.978. 2Amended by G.O.I. Notification No. F. 1-6/62-D dt 2.7.1969. 3Subs. by G.O.I. Notification No. GSR 647(E) dt 28.10.1998. 4Ins. by G.O.I. Notification No. GSR 665 dt 28.5.1977.
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1[124-C. Standards for Surgical Dressings. - The standards for Surgical Dressing shall be such as are laid down in Schedule F (II).]
2[124-D. Standards for Sterilised Umbilical tapes.- The standards for Sterilised Umbilical tapes shall be as laid down in Schedule F(III).]
3125. Standards for substances (other than food) intended to affect the structure or any function of human body—contraceptives—(1) The standards for mechanical contraceptives shall be such as are laid down in Schedule R.
(2) The standards which other contraceptives will have to comply with shall be in conformity with the formulae approved as safe and efficacious by the Central Government. Such formula shall be displayed on the label of every container of such contraceptive.
4[125-A. Standards for Medical Devices.- the standards for the Medical Devices shall be such as are laid down in Schedule R-1.]
5126. Standards for substances intended to be used for the destruction of vermin or insects which cause disease in human beings or animals.
Disinfectants. The standards of disinfectants shall be such as are laid down in Schedule O. 6126-A Standards for ophthalmic preparations7[including Homoeopathic
ophthalmic preparations] —The standards for ophthalmic preparations 7[including Homoeopathic ophthalmic preparations]shall be those laid down in Schedule FF., and such preparations shall also comply with the standards set out in the Second Schedule to the Act.
________________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 318(E0 dt 1.5.1984. 2 Ins. by G.O.I. Notification No. GSR 1115(E) dt 13.9.1986. 3 Amended by G.O.I. Notification No. F-1-28/65D dt 8.3.1966 4 Ins. by G.O.I. Notification No. GSR 109(E) dt 22.2.1994. 5 Amended by G.O.I. Notification No. F.1-20/60-D dt 24.1.1964. 6 Ins. by G.O.I. Notification No. 1-113/60-D dt 23.12.1969 7Subs. by G.O.I. Notification No. GSR 245(E) dt 17.6.1996.
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1127. List of colours permitted to be used in drugs—(1) No drug shall contain a colour other than specified below : --
(1) Natural Colours Annatto Carotene Chlorophyll Cochineal Curcumin Red Oxide of Iron Yellow Oxide of Iron 4Titanium Dioxide
2[Black Oxide of iron] (2) Artificial Colours
Caramel 3[Riboflavin]
(3) Coal Tar Colours
Common name of the colour
Colour Index Number
Chemical Name
1 2 3
GREEN Quinazarine Green S.S. 61565 1, 4-bis (p-Toluino) anthra-quinone
Alizarin Cyanine Green F. 61570 Disodium salt of 1, 4-bis (O-sulfo-p- Toluino) anthra-quinone
4Fast Green F.C.F. 42053 Disodium salt of 4-{[4-(N-ethyl- psulfobenzylamino)-phenyl-]-(4- hydroxy-2- sulfoniumphenyl)- methylene]
[1-(N-ethyl-N-p-sulfobenzyl]? 2, 5-cyclohexadienimine]-
[* * * Green S- Omitted by G.O.I. Notification No.GSR 753(E) dt 4.11.1999.]
YELLOW Tartrazine 19140 Trisodium salt of 3-carboxy-5-
Hydroxyl-1-p-sulfophenyl-4-p Sulfophenylazopyrazole
Sunset Yellow FCF 15985 Disodium salt of 1-p-sulfophenyl Azo- 2-naphthol-6-sulfonic acid.
________________________________________________________________________ 1Amended by G.O.I. Notification S.O.No. 289 dt 3.2.1973 2Ins. by G.O.I. Notification No. GSR 370(E) dt 7.4.1994. 3Ins. by G.O.I. Notification No. GSR 681(E) dt 6.6.1988. 4Ins. by G.O.I. Notification No. X.11013/3/76-DM.S dt 19.8.1978.
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1[Quinoline Yellow WS 47005 Disodium salt of disulfonic acid of 12-(2- quinolyl)-1, 3-indandione.
RED [* * * ‘Amaranth’-Omitted by G.O.I. Notification No.GSR 753(E) dt 4.11.1999.]
Erythrosine 45430 Disodium salt of 9-0-carboxypheny l6- hydroxy 2,4-5,7-tetriodo-3-isoxanthone
Eosin YS or Eosine G 45380 Disodium of salt of 2,4,5, 7-Tetrabromo 9- p-carboxyphenyl-6-hydroxy 3-isoxanthone.
Toney Red or Sudan III 26100 1-p-phenylazophenylazo-2-naphthol. Ponceau 4 R 16255 Trisodium salt of 1-(4-sulpho-1-1-
Napthylazo)-2 napthol-6 : 8-disulphonic acid.
Carmoisine 14720 Disodium salt of 2-(4-sulpho-1-nap- Thylazo)-1 napthol-4 sulphonic acid
[* * * ‘Fast Red’- Omitted by G.O.I. Notification No.GSR 753(E) dt 4.11.1999.]
BLUE
Indigo Carmine 73015 Disodium salt of indigotin-5 : -5 Disu
lphonic Acid
1Brilliant Blue FCF 42090 Disodium salt of 4-[ {4-(N-ethyl-p- sulfobenzylamino)-phenyl }-](2- sulfo -nium phenyl)-methylene)-1-(N- ethyl-N-p- sulfobenyl)- ? 2, 5-cyclohexadienimine
ORANGE Orange G 16230 Disodium salt of 1-phenylaze-2- naphthol-6,8-disulfonic acid. BROWN Resorcin Brown 20170 Monosodium salt of 4-p- sulfophenylazo-2-(2, 4-xylylazo)-1, 3 resorcinol.
BLACK Naphthol Blue Balck 20470 Disodium salt of 8-amino-7-p-nitro-phenylazo-2-phenylazo-1-naphthol-3, 6-
disulfonic acid.
______________________________________________________________________ 1Ins. by G.O.I. Notification No. X.11013/3/76 -DM.S dt 19.8.1978.
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(4) LAKES The Aluminum or calcium salts (lakes) of any of the water-soluble colours listed above.
(2) The label on the container of a drug containing a permitted colour shall indicate the common name of the colour.
128. The following rules are hereby repealed except as respect things done or omitted to be done under these rules, namely :---
Andhra Pradesh Drugs Rules, 1945. Assam Drugs Rules, 1945. Bihar Drugs Rules, 1945. Bombay Drugs Rules, 1946. East Punjab Drugs Rules, 1945. C.P. & Berar Drugs Rules, 1945. Madras Drugs Rules, 1945. Orissa Drugs Rules, 1945. Saurashtra Drugs Rules, 1953. Travancore-Cohin Drugs Rules, 1953. United Provinces Drugs Rules, 1945. West Bengal Drugs Rules, 1946. Mysore Drugs Rules, 1954.
1PART XIII-IMPORT OF COSMETICS
129. Statement to accompany imported cosmetics—All consignments of cosmetics sought to be imported shall be accompanied by an invoice or statement showing the name and quantities of each article of cosmetic included in the consignment and the name and address of the manufacturer.
130. Documents to be supplied to the Collector of Customs—Before any cosmetics are imported, a declaration signed by or on behalf of the manufacturer or by on behalf of the importer that the cosmetics comply with the provisions of Chapter III of the Act, and the Rules made there under, shall be supplied to the Collector of Customs.
131. Procedure for the import of cosmetics. - If the officer appointed at the post of entry by the Central Government has reason to believe that any cosmet ic contravenes any of the provisions of the Act or the rules made thereunder he may take sample of the cosmetic from the consignment for inspection. If on examination of the sample defects are noticed the officer shall advise the Collector of customs for further action to be taken.
______________________________________________________________________ 1Added under G.O.I. Notification No. F. 1-36/64-D, dated 17-8-1961.
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If the suspected contravention of the provisions of the Act or the Rules is such as may have to be determined by test, the officer shall send the sample to the laboratory established for the purpose for performing such that the test report on such sample is received from the Director of the said laboratory or any other officer of the laboratory empowered by him in this behalf with the approval of the Central Government.
Provided that if the importer gives an undertaking in writing not to dispose of the cosmetic without the consent of the Collector of Customs and to return the consignmentor such portion thereof, he shall return the consignment or such portion thereof as may be required, the Collector of Customs shall make over the consignment to the importer.
(2) If the importer who has given an undertaking under the proviso to sub-rule (1) is required by the Collector of Customs to return the consignment or portion thereof, he shall return the consignment or portion thereof within ten days of receipt of the notice.
Further procedure on receipt of the report of analysis
(3) If the Direc tor of the Laboratory established for the purpose by the Central Government or any other officer of the laboratory empowered by him in this behalf with the approval of the Central Government, reports to the Collector of Customs or to the officer mentioned in sub-rule (1) above that the sample of any cosmetic in a consignment contravenes the provisions of Chapter III of the Act or the Rules made there under and that the contravention is such that it cannot be remedied by the importer, the Collector of Customs shall communicate the report forthwith to the importer who shall within two months of receiving such a communication either send back all cosmetic of that description to the country in which it was manufactured or to the country from which it was imported or hand it over to the Central Government which shall cause it to be destroyed.
Provided that the importer may within thirty days of receipt of the report make a representation against the report to the Collector of Customs who shall forward the representation with a fresh sample of the cosmetic to the Drugs Controller, India, who after obtaining, if necessary, the report of the Director of the Central Drugs Laboratory shall pass orders thereon which shall be final.
(4) If the Drugs Controller or any other empowered by him in this behalf with the approval of Central Government reports to the Collector of Customs after the inspection of the sample of cosmetic and if necessary, after obtaining a test report thereon that the sample of the said cosmetic contravenes in any respect the provisions of Chapter III of the Act or the Rules made thereunder but that the contravention is such that it can be remedied by the importer, the Collector of Customs shall communicate the report forthwith to the importer and permit him to import the cosmetic on his giving an undertaking in writing not to dispose of the cosmetic without the permission of the officer authorised in this behalf by the Central Government.
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132. Exemption of cosmetics—Cosmetics as may be specified in Schedule D shall be exempted from the provisions of Chapter III of the Act and the Rules made thereunder to the extent and subject to the conditions specified in that Schedule.
133. Import through points of entry—No cosmetic shall be imported into India except through the points of entry specified in rule 43A.
1[134. Cosmetic to contain Dyes, Colours and Pigments.- No Cosmetic shall contain Dyes, Colours and Pigments other than those specified by the Bureau of Indian Standards (IS:4707 Part 1 as amended) and Schedule Q.
The permitted Synthetic Organic Colours and Natural Organic Colours used in the Cosmetic shall not contain more than:-
(i) 2 parts per million of Arsenic calculated as Arsenic Trioxide. (ii) 20 parts per million of lead calculated as lead. (iii)100 parts per million of heavy metals other than lead calculated as
the total of the respective metals.]
2134-A Prohibition of import of cosmetic containing Hexachlorophene— No cosmetic containing hexachlorophene shall be imported.
135. Import of cosmetic Lead or Arsenic compound prohibited—No cosmetic shall be imported in which a Lead or Arsenic compound has been used for purposes of colouring.
3135-A. Import of cosmetics containing mercury compounds prohibited. No cosmetic shall be imported which contains mercury compounds.
136. Import of cosmetic for personal use—Small quantities of cosmetics the import of which is otherwise prohibited under section 10 of the Act, may be imported for personal use subject to the following conditions: —
(j) The cosmetics shall form part of a passenger’s baggage and shall be the property of and intended for, the bonafideuse of the passenger; and
(ii) The cosmetics shall be declared to the Customs authorities, if they so direct.
4[PART XIV—MANUFACTURE OF COSMETIC FOR SALE OR FOR DISTRIBUTION]
________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 811(E) dt 14.11.1994. 2Added by G.O.I. Notification No. G.S.R. 116 dated 25-1-1975. 3 Ins. by G.O.I. Notification No. X.11013/76-D & MS dt 19.8.1978. 4 Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985.
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137. Manufacture on more than one set of premises—If cosmetics are manufactured on more than one premises, a separate application for each such premises shall be made and a separate licence obtained for each such premises.
138. Application for licence to manufacture cosmetics—(1) Application for grant or renewal of licence to manufacture any cosmetic for sale 1[shall be made up to ten items of each category of cosmetics categorized in Schedule M-II to the Licensing Authority appointed by the State Government for the purpose of this Part (hereafter’ in this Part referred to as the Licensing Authority) in Form 31 and shall be accompanied by a fee of rupees two thousand and five hundred and an inspection fee of rupees one thousand for every inspection thereof or for the purpose of renewal of licence.]
[* * * Omitted as per G.O.I. Notification No. GSR 331-E dt 8.5.1984] .
(2) If a person applies for the renewal of licence after expiry but within six months of such expiry, the fee payable for the renewal of such licence shall be 1[rupees two thousand five hundred plus an additional fee at the rate of rupees four hundred per month or part thereof in additional to an inspection fee of rupees one thousand.]
[* * * Omitted as per G.O.I. Notification No. GSR 331-E dt 8.5.1984]
(3) Application by a licensee to manufacturer additional items of cosmetics shall be accompanied by a fee of 1[rupees one hundred for each item subject to a maximum of rupees three thousand for each application.]
[* * * Omitted as per G.O.I. Notification No. GSR 331-E dt 8.5.1984]
(4) A fee of 1[rupees two hundred and fifty] shall be paid for a duplicate copy of a licence under sub-rule (1) and the proviso to sub-rule (1) respectively if the original is defaced, damaged or lost.
2138-A Application for loan licence to manufacture cosmetics .- (1) Application for grant or renewal of a loan licence for the manufac ture for sale of
cosmetics 1[shall be made up to ten items of each category of cosmetics categorized in Schedule M-II in Form 31-A to the Licensing Authority and shall be accompanied by a licence fee of rupees two thousand and five hundred and an inspectio n fee of rupees one thousand foe every inspection thereof].
Explanation—For the purpose of this rule a ‘loan licence’ means a licence, which a Licensing Authority may issue to an applicant who does not have his own arrangements to manufacture but who intends to avail himself of the manufacturing facilities owned by a licensee in Form 32.
______________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001. 2 Ins. by G.O.I. Notification No. GSR 444 dt 28.4.1973.
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(2) If a person applies for the renewal of a loan licence after the expiry but within six months of such expiry, the fee payable for the renewal of such a licence 1[shall be rupees two thousand and five hundred plus an additional fee at the rate of rupees four hundred for each month or part thereof.]
(3) The Licensing Authority shall before the grant of a loan licence satisfy himself that the manufacturing unit has adequate equipments, staff, capacity for manufacture and facilities to undertake the manufacture on behalf of the applicant for a loan licence.
(4) The loan licence shall be granted by the Licensing Authority to only such applicants who propose to avail of the facilities of manufacture of cosmetics in the premises of a manufacturer located in the same State where the applicant is located. In case the manufacture of cosmetic involves any special process of manufacture or use of equipments which are not available in the State where the applicant is located, the Licensing Authority after consulting the Licensing Authority where the manufacturing unit is located, may grant the loan licence.
(5) Subject to the provisions of sub-rule (2), application for manufacture of additional items on a loan licence shall be accompanied by fee of 1[rupees one hundred for each item subject to a maximum of rupees three thousand per application.]
(6) A fee of 1[rupees two hundred and fifty] shall be paid for a duplicate copy of a licence issued under sub-rule (1) if the original is defaced, damaged or lost;
139. Conditions for the grant or renewal of a licence in Form 32—Before a licence in Form 32 is granted or renewed, the following conditions shall be compiled with by applicant:
(1) The manufacture shall be conducted under the direction and personal supervision of a competent technical staff consisting of at least one person who is a whole time employee and who possesses any one of the following qualifications:
(a) holds a Diploma in Pharmacy approved by the Pharmacy Council of India under the Pharmacy Act, 1948 (8 of 1948), or .
(b) is registered under the Pharmacy Act, 1948 (8 of 1948), or
(c) has passed the Intermediate Examination with Chemistry as one of the subjects or an examination recognized by the Licensing Authority as equivalent to it.
[* * * Omitted as per G.O.I. Notification No. GSR 331-E dt 8.5.1984] [* * * Omitted as per G.O.I. Notification No. GSR 331-E dt 8.5.1984]
______________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001.
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.
1[(2) The factory premises shall comply with the requirements and conditions specified in Schedule M-II.
[* * * Omitted as per G.O.I. Notification No. GSR 723-E dt 11.8.1982.] [* * * Omitted as per G.O.I. Notification No. GSR 723-E dt 11.8.1982.]
(5) The applicant shall either--
(i) provide and maintain adequate staff, premises and laboratory equipment for testing the cosmetic manufactured, and the raw materials used in the manufacture; or
(ii) make arrangements with some institution appro ved by the Licensing Authority under Part XV (A) of these rules for such tests to be regularly carried out in this behalf by the institution.
2139-A Form of 3[ licence to manufacture cosmetics for sale or for distribution]—A 3[licence to manufacture cosmetic for sale or for distribution] against application in Form 31, shall be granted in Form 32.
4[139AA.Inspection before grant or renewal of licence.- Before a licence under this part is granted or renewed in Form 32, Form 32-A or Form 3, the Licensing Authority shall cause the establishment, in which the manufacture is proposed to be conducted or being conducted, to be inspected by one or more Inspectors appointed under the Act. The Inspector or Inspectors shall examine all portions of the premises, plant and appliances and also inspect the process of manufacture intended to be employed or being employed along with the means to be employed or being employed for standardizing and testing the substances to be manufactured and enquire into the professional qualifications of the technical staff to be employed. He shall also examine and verify the statements made in the application in regard to their correctness, and the capability of the applicant to comply with the requirements of competent technical staff, manufacturing plant, testing equipments and the requirements of plant and equipments as laid down in Schedule M-II read with requirements of maintenance of records as laid down in Schedule U-1.
139AB. Report by Inspector.- The Inspector or Inspectors shall forward a detailed descriptive report giving his or their findings on each aspect of inspection along with his or their recommendations after completion of his or their inspection to the Licensing Authority.
________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 723(E) dt 11.8.1992. 2Ins. by G.O.I. Notification No. GSR 444 dt 28.4.1973. 3Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 4Ins. by G.O.I. Notification No.493(E) dt 9.6.1995.
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139AC. Grant or refusal of licence.- (1) If the Licensing Authority after such further enquiry, if any as he may consider necessary is satisfied that the requirements of the rules under the Act have been complied with and that the conditions of the licence and the rules under Act shall be observed, he shall grant or renew a licence inform 32, Form 32-A or Form 33.
(2) If the Licensing Authority is not so satisfied, he shall reject the application and shall inform the applicant of the reasons for such rejection and of the conditions which must be satisfied before a licence can be granted or renewed and shall supply the applicant with a copy of inspection report.
130AD. Further application after rejection.- If within a period of six months from the rejection of an application for a licence, the applicant informs the Licensing Authority that the conditions laid down have been fulfilled and deposits an inspection 1[a fee of rupees two hundred and fifty], the Licensing Authority may, if, after causing further inspection to be made, he is satisfied that the conditions for the grant of licence have been complied, with issue a licence in Form 32, Form 32-A or Form 33.
139AE. Appeal to the State Government.- Any person who is aggrieved by the order passed by the Licensing Authority refusing to grant or renew a licence under this Part may, within ninety days from the date of receipt of such order, appeal to the State Government and the State Government may, after such enquiry into the matter as is considered necessary and after giving the said person an opportunity for representing the case, pass such order as it thinks fit.]
2139-B Form of loan 3[licence to manufacture cosmetics for sale or for distribution]—A loan 3[licence to manufacture cosmetics for sale or for distribution] against application in Form 31-A shall be granted in Form 32-A.
140 Duration of licence. - An original licence or a renewal licence shall unless sooner suspended or cancelled be 1[valid for a period of five years and on from the date on which] it is granted or renewed.
4Provided that if the application for renewal of a licence in force is made before its expiry or if the applications is made within six months of its expiry, after payment of additional fee, the licence shall continue to be in force until orders are passed on the application for its renewal is not made within six months of its expiry.
141. Certificate of renewal—The certificate of renewal of a licence in Form 32 shall be issued in Form 33. ______________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 723(E) dt 11.8.1992. 2Ins. by G.O.I. Notification No. GSR 444 dt 28.4.1973. 3Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 4 Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001.
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1141-A Certificate of renewal of a loan licence—The certificate of renewal of a licence in Form 32-A shall be issued in Form 330A.
1141-AA Duration of a loan licence—An original loan licence in Form 32-A or a renewed loan licence in Form 33-A, unless sooner suspended or cancelled, shall be 2[valid for a period of five years on and from the date on which] it is granted or renewed.
Provided that if the application for the renewal of a licence is made before its expiry, or if the applic ation is made within six months of its expiry, after payments of the additional fee, the licence shall continue to be in force and orders are passed on the application. The licence shall be deemed to have expired if the application for its renewal is not made within six months of expiry.
142. Conditions of licence—A licence in Form 32 shall be subject to the conditions stated therein and to the following other conditions, namely:—
(a) the licensee shall provide and maintain staff, premises and equipment as specified in rule 139.
(b) The licensee shall comply with the provisions of the Act and the Rules made thereunder and with such further requirements, if any, as may be specified in any rules to be made hereafter under Chapter IV of the Act.
3(b-1) the licensee shall keep records of the details of each batch of cosmetic manufactured by him and of raw materials used therein as per particulars specified in Schedule U(1) and such records shall be retained for a period of three years.
(c) The licensee shall test eac h batch or lot of the raw materials used by him for the cosmetics and also each batch of the final product and shall maintain records or registers showing the particulars in respect of such tests. The records or registers shall be retained for a period of three years from the date of manufacture.
(d) The licensee shall allow any Inspectors appointed under the Act to enter with or without prior notice any premises where the manufacture of a substance in respect of which the licence is issued is carried on, to inspect the premises and to take samples of the manufactured products under a receipt.
_______________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 444 dt 28.4.1973 2Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001. 3Ins. by G.O.I. Notification No. GSR 1594 dt 13.11.9176.
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(e) The licensee shall allow an Inspector to inspect all registers and records maintained under these rules and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and the Rules made thereunder have been complied.
1(f) The licensee shall maintain an Inspection Book in Form 35 to enable an Inspector to record his impression and the defects noticed.
2[Provided that clauses (b -1) and (c) shall not apply to the manufacture of soap and the procedure for testing of raw materials and the records to be maintained by the manufacturer of soap shall be such as are approved by the Licensing Authority.]
3142-A Additional information to be furnished by an applicant for licence or a licensee to the Licensing Authority.—The applicant for the grant of a licence or any person granted a licence under this Part shall, on demand; furnish to the Licensing Authority, before the grant of the licence or during the period of licence is in force, as the case may be, documentary evidence in respect of the ownership or occupation on rental or other basis of the premises specified in the application for licence or in the licence granted, constitution of the firm, or any other relevant matter, which may be required for the purpose of verifying the correctness of the statements made by the applicant or the licensee, while applying for or after obtaining the licence as the case may be.
1142-B Conditions of licence in Form 32-A.- (a) A licence in Form 32-A shall be deemed to be cancelled or suspended, if the
licence owned by the licensee, in Form 32, whose manufacturing facilities are cancelled or suspended, as the case may be under these Rules.
(b) The licensee shall comply with the provisions of the Act and these rules and with each further requirements, if any, as may be specified from time to time in Chapter IV of the Act, provided that where such further requirements are specified in the rules, these would come into force four months after publication in the Official Gazette.
5(b-1)the licensee shall keep records of the details of each batch of cosmetic manufactured by him and of raw materials used therein as per particulars specified in Schedule U (1) and such records shall be retained for a period of three years.
(c) The licensee shall test each batch or lot of the raw materials used by him for the manufacture of the cosmetics and also each batch of the final product and shall
______________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 444 dt 28.4.1973 2Ins. by G.O.I. Notification No. GSR 681(E) dt 6.6.1988. 3 Ins. by G.O.I. Notification No. S.O.2139 dt 12.8.1972. 4Ins. by G.O.I. Notification No. GSR 1594 dt 13.11.9176.
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maintain records of registration showing the particulars in respect of such tests. The records or registers shall be retained for a period of three years from the date of manufacture.
(d) The licensee shall allow an Inspector appointed under the Act to enter with or without prior notice any premises where the manufacture of a substance in respect of which licence is issued is carried on, to inspect the premises and to take samples of the manufactured products under a receipt.
(e) The licensee shall allow an Inspector to inspect all registers and records maintained under these rules and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act, and the rules made thereunder have been compiled.
(f)The licensee shall maintain an Inspection Book in Form 35 to enable an Inspector to record his impressions and the defects noticed.
143. Cancellation and suspension of licence.—(1) The Licensing Authority may, after giving the licensee an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefore, cancel a licence issued under this Part or suspend it for such period as he thinks fit, either wholly or in respect of some of the substances to which it relates, if in his opinion, the licensee has failed to comply with any of the conditions of the licence or with any provisions of the Act or the rules made thereunder.
(2) A licensee whose license has been suspended or cancelled may appeal with in a period of three months from the date of the order to the State Government which shall after considering the appeal, pass orders, and such orders shall be final.
1[144. Prohibition of manufacture of cosmetics containing colours other than those prescribed.- No Cosmetic shall be manufactured which contains Dyes, Colours and Pigments other than the one specified by the Bureau of Indian Standards (IS: 4707 Part I as amended) and Schedule Q.
The permitted Synthetic Organic colours and Natural Organic colours used in the Cosmetic shall not contain more than :
(i) 2 parts per million of arsenic calculated as arsenic trioxide. (ii) 20 parts per million of lead calculated as lead. (iii) 100 parts per million of heavy metals other than lead calculated as
the total of the respective metals.]
2144-A. Prohibition of manufacture of cosmetics containing Hexachlorophene.—No cosmetic contain ing Hexachlorophene shall be manufactured. _______________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 811(E) dt 14.11.1994. 2 Ins. by G.O.I. Notification No. GSR 116 dt 25.1.1975.
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1[Provided that in the case of soaps hexachlorophene may be used in concentrations not exceeding one per cent weight by weight.
Provided further that the following cautionary note shall be printed and shall appear in a conspicuous manner on the wrapper of package of each soap, namely:-
“Contains hexachlorophene – not to be used on babies”.]
145. Use of Lead and Arsenic compounds for the purpose of colouring cosmetics prohibited.—The use of Lead and Arsenic compounds for the purpose of colouring cosmetics is prohibited.
2145-A. Form of intimation for purpose of taking samples of cosmetics.—Where an Inspector takes a sample of a cosmetic for the purpose of test or analysis, he shall intimate such purpose in writing in Form 17 to the person from whom he takes it.
3[145-AA. Form of receipt of samples of cosmetics where fair price tendered is refused.- Where the fair price, for the samples of Cosmetics taken for the purpose of test or analysis, tendered under sub-section (1) of Section 23 has been refused, the Inspector shall tender a receipt therefore to the person from whom the said samples have been taken as specified in Form 17-A.]
145-B. Form of receipt for seized cosmetics.—A receipt by an Inspector for the stock of any cosmetic seized under clause (c) of sub-section (1) ofsection 22 of the Act, shall be in Form 15.
4[145-BA Manner of certifying copies of seized documents.- The Drugs Inspector shall return the documents, seized by him under clause (cc) or produced before him under clause (cca) of sub-section (1) of Sectio n 22 of the Act, within a period of twenty days of the date of such seize or production, to the person from whom they were seized or, as the case may be, the person who produced them, after copies thereof or extracts therefrom have been signed by the Drugs Inspector concerned and the person from whom they were seized, or, as the case may be, who produced such records.]
5145-C Form of order not to dispose of stocks of cosmetics—An order in writing by an Inspector under clause (c) of sub-section (1) of Section 22 of the Act requiring a person not to dispose of any stock of cosmetics in his possession shall be in Form 15.
______________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 1049(E) dt 29.8.1986. 2 Added by G.O.I. Notification No. S.O. 2139 dtd 12.8.1972. 3 Ins. by G.O.I. Notification No. GSR 292(E) dt 29.5.1997 4 Ins. by G.O.I. Notification No. GSR 89(E) dt 16.2.1985. 5 Ins. by G.O.I. Notification No. GSR 1594 dt 13.11.9176.
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1145-D Prohibition of manufacture of cosmetics containing mercury compounds—No cosmetics containing mercury compounds shall be manufactured.
PART XV—LABELLING, PACKING AND STANDARDS OF COSMETICS
146. Prohibition of sale or distribution—Subject to other provisions of these rules, no person shall sell or distribute any cosmetic unless the cosmetic, if of Indian origin is manufactured by a licensed manufacturer and labelled and packed in accordance with these rules.
2[147. Exemption of cosmetics not manufactured for consumption or sale in India from the provisions of this Part.- Labels on packages or containers of cosmetics not manufactured for consumption or sale in India shall be adapted to meet the specific requirements, if any, of the consignee.
Provided that where a cosmetic is required by the consignee to be not labeled with the name and address of the manufacturer, the labels on packages or containers shall bear a code number as approved by the Licensing Authority mentioned in Rule 21.]
148. Manner of labelling—Subject to other provisions of the rules, a cosmetic shall carry.-
(1) On both the inner and outer labels;
(a) The name of the cosmetic, 3[(b) The name of the manufacturer and complete address of the
premises of the manufacturer where the cosmetic has been manufactured.
Provided that if the cosmetic is contained a very small size container where the address of the manufacturer cannot be given, the name of the manufacturer and his principal place of manufacture shall be given along with pin code.]
(2) On the outer label-
A declaration of the net contents expressed in terms of weight for solids, fluid measure for liquids, weight for semi solids, combined with numerical court if the content is sub-divided:
________________________________________________________________________ 1 Ins. by G.O.I. Notification No. X.11013/3/76-D&MS dt 19.8.1978. 2Subs. by G.O.I. Notification No. GSR 682(E) dt 5.12.1980 3 Subs. by G.O.I. Notification No. GSR 352(E) dt 26.4.2000.
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Provided that this statement need not appear in case of a package of perfume, toilet water or the like the net content of which does not exceed 60ml or any package of solid or semi-solid cosmetic the net content of which does not exceed 30 grams.
(3) On the inner label, where a hazard exists— (a) Adequate direction for safe use. (b) Any warning, caution or special direction required to be observed by
the consumer, (c) A statement of the names and quantities of the ingredients that are
hazardous or poisonous.
1(4) A distinctive batch number, that is to say, the number by reference to which details of manufacture of the particular batch from which the substance in the container is taken are recorded and are available for inspection, the figures representing the batch number being preceded by the letter “B”, provided that this clause shall not apply to any cosmetic containing 10grams or less if the cosmetic is in solid or semi-solid state, and 25 milliliters or less if the cosmetic is in a liquid state.
2[Provided further that in the case of soaps, instead of the batc h number, the month and year of manufacture of soap shall be given on the label.]
3(5) manufacturing licence number, the number being preceded by the letter ‘M’.
(6) Where a package of a cosmetic has only one label, such label shall contain all the information required to be shown on both the inner and the outer labels, under these Rules.
4[148-A. Prohibition against altering inscriptions on containers, labels or wrappers of cosmetics.- No person shall alter, obliterate or deface any inscription or mark made or recorded by the manufacturer on the container, label or wrapper of any cosmetic.
Provided that nothing in this rule shall apply to any alteration, inscription or mark made on the container, label or wrapper of any cosmetic at the instance or direction or with the permission of the licensing authority.]
149. 5[Labelling of Hair dyes containing Dyes, Colours and Pigments.—Hair dyes containing Para-Phenylenediamine or other Dyes, Colours and Pigments] shall be labelled with the following legend in English and local languages and these shall appear on both the inner and the outer labels. ________________________________________________________________________ 1Amended by G.O.I. Notification No. GSR 245 dt 21.2.1976. 2Ins. by G.O.I. Notification No. 681(E) dt 6.8.1988. 3Amended by G.O.I. Notification No. GSR 245 dt 21.2.1976 4Ins. by G.O.I. Notification No.GSR 351(E) dt 26.4.2000. 5Subs. by G.O.I. Notification No.GSR 811(E) dt 14.11.1994.
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“Caution—This product contains ingredients which may cause skin irritation in certain cases and so a preliminary test according to the accompanying direction should first be made. This product should not be used for dyeing the eye-lashes or eye-brows; as such a use may cause blindness”.
Each package shall also contain instructions in English and local languages on the following lines for carrying out the test:
“This preparation may cause serious inflammation of the skin in some cases and so a preliminary test should always be carried out to determine whether or not special sensitivity exists. To make the test, cleanse a small area of skin behind the ear or upon the inner surface of the forearm, using either soap and water or alcohol. Apply a small quantity of the hair dye as prepared for use to the area and allow it to dry. After twenty-four hours, wash the area gently with soap and water. If no irritation or inflammation is apparent, it may be assumed that no hypersensitivity to the dye exists. The test should, however, be carried out before each and every applic ation. This preparation should on no account be used for dyeing eye-brows or eye-lashes as severe inflammation of the eye or even blindness may result”.
1[149-A. Special provisions relating to toothpaste containing fluoride. -
(i) Fluoride content in toothpaste shall not be more than 1000 ppm and the content of fluoride in terms of ppm shall be mentioned on the tube and carton.
(ii) Date of expiry should be mentioned on tube and carton.]
150. Report of result of test or analysis of cosmetics—Test reports on samples of cosmetics taken for test or analysis under these Rules shall be supplied in Form 34.
2[150-A. Standard for cosmetics.- Subject to the provisions of these rules, the standards for cosmetics shall be such as may be prescribed in Schedule S.]
3PART XV (A) APPROVAL OF INSTITUTIONS FOR CARRYING OUT TESTS ON DRUGS, COSMETICS AND RAW MATERIALS USED IN THEIR
MANUFACTURE ON BEHALF OF LICENSEES FOR MANUFACTURE FOR SALE OF DRUGS / COSMETICS.
150-B. Application for grant for testing drugs / cosmet ics— __________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 223(E) dt 19.4.1991. 2 Ins. by G.O.I. Notification No. GSR 510(E) dt 26.7.1982.. 3 Ins. by G.O.I. Notification No. X.1104/7/76-D&M dt 23.8.1977.
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(1) Application for grant or renewal of approval for carrying out tests for identity, purity, quality and strength on drugs or cosmetics or the raw materials used in the manufacture thereof on behalf of licensees for manufacture for sale of drugs or cosmetics, shall be made in Form 36 to the Licensing Authority appointed by the State Government for the purposes of Part VII, VII (A) or XIV of these Rules, as the case may be and referred to as the “approving authority” under this Part and shall be accompanied by an inspection fee of 1[rupees six thousand] in the case of testing of drugs specified in Schedules C and C (1) and 1[rupees one thousand five hundred] in the case of testing of drugs other than those specified in Schedule C and C (1), homoeopathic drugs and cosmetics.
Provided that the applicant shall furnish to the approving authority such additional information as may be required by him in connection with the application in Form 36;
1[Provided further that if the applicant applied for renewal of approval after its expiry but within six months of such expiry, the inspection fee payable shall be rupees six thousand in the case of testing of drugs specified in Schedule C and C (1) and rupees one thousand five hundred in the case of testing of drugs other than those specified in Schedule C and C (1), Homoeopathic medicines and cosmetics plus an additional fee at the rate of rupees one thousand per month.]
(2) A separate application shall be made for grant of approval for carrying out tests on addit ional categories of drugs or items of cosmetics and shall be accompanied by an inspection fee of rupees one thousand five hundred in the case of drugs specified in Schedule C and Schedule C(1) and rupees one thousand each in case of drugs other than those specified in Schedule C and Schedule C(1), homeopathic medicines and cosmetics.
Explanation—For the purpose of this Part, the words ‘drugs’ and ‘cosmetics’ shall also mean and include the raw materials used in the manufacture of drugs including Homoeopathic drugs or cosmetics, as the case may be.]
150-C. Form on which approval to be granted for carrying out tests on drugs / cosmetics on behalf of licensees for manufacture of drugs/cosmetics and conditions for grant or renewal of such approval—
(1) Approval for carrying out such tests of identity, purity, quality and strength of drugs or cosmetics as may be required under the provisions of these rules, ob behalf of licensee for manufacture of drugs or cosmetics shall be granted in Form 37.
(2) Before ap proval in Form 37 is granted or renewed, the following conditions shall be compiled with by the applicant—
______________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001.
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(1) The premises where the tests are being carried out shall be well lighted and properly ventilated except where the nature of tests of any drug or cosmetic warrants otherwise. Wherever necessary, the premises shall be air conditioned so as to maintain the accuracy and functioning of laboratory instruments or to enable the performance of special tests such as sterility tests, microbiological tests etc.
2) The applicant shall provide adequate space having regard to the nature and number of samples of drugs or cosmetics proposed to be tested;
Provided that the approving authority shall determine from time to time whether the space provided continues to be adequate.
3) If it is intended to carry out tests requiring the use of animals, the applicant shall provide for an animal house and comply with the following requirements. (a) The animal house shall be adequate in area, well lighted and
properly ventilated and the animals undergoing tests shall be kept in air conditioned area.
(b) The animals shall be suitably housed in hygienic surroundings and necessary provisions made for removal of excreta and foul smell.
(c) The applicant shall provide for suitable arrangements for preparation of animal feed.
(d) The applicant shall provide for suitable arrangements for quarantining of all animals immediately on their receipt in the institution.
(e) The animals shall be periodically examined for their physical fitness
(f) The applicant shall provide for isolation of sick animals as well as animals under test.
(g) The applicant shall ensure compliance with the requirements of the Prevention of Cruelty to Animal Act, 1960 (59 of 1960).
(h) The applicant shall make proper arrangements for the disposal of the carcasses of animals in a manner as not to cause to public health.
(4) The applicant shall provide and maintain suitable equipment having regard to the nature and number of samples of drugs or cosmetics intended to be tested which shall be adequate in the opinion of the approving authority.
(5) The testing of drugs or cosmet ics, as the case may be shall be under the active direction of a person whose qualifications and experience are considered adequate in the opinion of the approving authority and who shall be held responsible for the reports of test or analysis issued by the applicant.
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(6) The testing of drugs or cosmetics, as the case may be, for identity, purity, quality and strength shall be carried out by persons whose qualifications and experience of testing are adequate in the opinion of the approving authority.
(7) The applicant shall provide books of standard recognized under the provisions of the Act and the Rules made thereunder and such books of reference as may be required in connection with the testing or analysis of the products for the testing of which ap proval is applied for.
150-D: Duration of approval: An approval granted in Form 37 or renewed in Form 38, unless sooner suspended or withdrawn, shall be 1[valid for a period of five years on and from the date on which] it is granted or renewed:
Provided that if an application for the renewal of an approval in Form 37 is made before its expiry or if the application is made within six months of its expiry after the payment of the additional fee, the approval shall continue to be in force until orders are passed on the applications and the approval within six months of its expiry.
150E: Conditions of approval: An approval in Form 37 shall be subject to the following general conditions: —
(a) The institution granted approval under this Part (hereinafter referred to as the approved institution) shall provide and maintain an adequate staff and adequate premises and equipment as specified in rule 150-C.
(b) The approved institution shall provide proper facilities for storage so as to preserve the properties of the samples of the samples to be tested by it.
(c) The approved institution shall maintain records of tests for identity, purity, quality and strength carried out on all samples of drugs or cosmetics and the results thereof together with the protocols of tests showing the readings and calculation in such form as to be available for inspection and such records shall be retained in the case of substances for which an expiry date is assigned for a period of two years from the expiry of such date and in the case of other substances for a period of six years.
(d) The approved institution shall allow the Inspector appointed under this Act to enter with or without prior notice the premises where the testing is carried on and to inspect the premises and the equipment used for test and the testing procedures employed. The institution shall allow the Inspectors to inspect the registers and records maintained under these Rules and shall supply to such
______________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001.
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Inspectors such information as they may require for the purpose of ascertaining whether the provisions of the Act and Rules made thereunder have been observed.
(e) The approved institution shall from time to time report to the approving authority any changes in the person-in-charge of testing of drugs or cosmetics or in the expert staff responsible for testing as the case may be and any material alteration in the premises or changes in the equipment used for the purposes of testing which have been made since the date of last inspection made on behalf of the approving authority before the grant or renewal of approval.
(f) The approved institution shall furnish reports of the results of test or analysis in Form 39.
(g) In case any sample of a drug or a cosmetic is found on test to be not of standard quality, the approved institution shall furnish the approving authority 1[and the licensing authority of the State where the manufacturer and/or sender of the drug or cosmetic is located] with copy of the test report on the sample with the protocols of tests applied.
(h) The approved institution shall comply with the provisions of the Act and Rules made thereunder and with each further requirements, if any, may be specified in the rules subsequently made under Chapter IV of the Act of which the approving authority has given the approved institution not less than four months notice.
(i) The approved institution shall maintain an Inspection Book to enable the Inspectors to record his impression or defects noticed.
150-F:Inspection before grant of approval: Before an approval in Form 37 is granted, the approved authority shall cause the institution at which the testing of drugs or cosmetics, as the case may be, is proposed to be carried out to be inspected jointly by the Drugs Inspectors of the Central Drugs Standard Control Organisation and the State Drugs Control Organisation who shall examine the premises and the equipment intended to be used for testing of drugs or cosmetics and inquire into the professional qualifications of the expert staff to be employed.
150-G: Report of Inspection : The Drug Inspector mentioned in rule 150-F shall forward to the appointing authority a detailed report of the result of the inspection.
______________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 93(E) dt 24.2.1995.
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150-H: Procedure of approving authority: (1) If the approving authority after such further enquiry, if any, as he may consider necessary, is satisfied that the requirements of the rules made under the Act have been compiled with and that the conditions of the approval and the Rules made under the Act will be observed, he shall grant an approval in Form 37.
(2) If the appointing authority is not so satisfied, he shall reject the application and shall inform the applicant of the reasons for such rejections and of the conditions, which must be satisfied before an approval could be granted.
150-I: Further application after rejection : If within a period of six months from the rejection for approval, the applicant informs the approving authority that the conditions laid down have been satisfied and deposits inspection fee of 1[rupees two hundred and fifty], the approving authority mat, if, after causing a further inspection to be made, satisfied that the conditions for grant of approval have been compiled with, grant the approval in Form 37.
150-J: Renewal: On an application being made for renewal the approving authority may cause an inspection to be made and if satisfied that the conditions of the approval and the Rules made under the Act are and shall continue to be observed shall issue a certificate of renewal in Form 38.
150-K: Withdrawal and suspension of approvals: (1) The approving authority may, after the approved institution an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefore, withdraw an approval granted under this Part or suspend it for such period as he th inks fit either wholly or in respect of some of the categories of drugs or items of cosmetics to which it relates, if in his opinion the approved institution has failed to comply with any of the conditions of the approval or with any provisions of the Act or the Rules made thereunder.
(2) Any approved institution whose approval has been suspended or withdrawn may within three months of the date of the order, appeal to the State Government which shall dispose of the appeal in consultation with a panel of competent persons appointed by it in this behalf and notified in the Official Gazette.
2PART XVI—MANUFACTURE FOR SALE OF AYURVEDIC (INCLUDING SIDDHA) OR UNANI DRUGS .
151. manufacture on more than one set of premises—If Ayurvedic (including Siddha) or Unani drugs are manufactured are manufactured on more than one set of premises, a separate applications shall be made and a separate licence shall be obtained in respect of each such set of premises. ______________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 601(E) dt 24.8.2001. 2 Added under G.O.I.Notification No. 1-23/67-D dated the 2-2-1970.
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152. Licensing Authorities—Fore the purpose of this Part the State Government shall appoint such Licensing Authorities and for such areas as may be specified in this behalf by notification in the Official Gazette.
153. Application for licence to manufacture Ayurvedic (including Siddha) or Unani drugs.—(1) An application for the grant or renewal of a licence to manufacture for sale any Ayurvedic (including Siddha) or Unani drugs shall be made in Form 24-D to the Licensing Authority alongwith a fee of rupees sixty.
Provided that in the case of renewal the applicant may apply for the renewal of the licence before its expiry or within one month of such expiry:
Provided further that the applicant may apply for renewal after the expiry of one month but within three months of such expiry in which case the fee payable for renewal of such licence shall be rupees thirty.
(ii) A fee of rupees fifteen shall be payable for a duplicate copy of a licence issued under this rule, if the original licence is defaced, damaged or lost.
1153-A. Loan Licence.—(i) An application for the grant of renewal of a loan licence to manufacture for sale of any Ayurvedic (including Siddha) or Unani drugs shall be made in Form 25-E to the Licensing Authority along with a fee of rupees thirty.
Explanation—For the purpose of this rule, a loan licence means a licence which a Licensing Authority may issue to an applicant who does not have his own arrangements for manufacture but intends to avail himself of the manufacturing facilities owned by a licence in Form 25-D:
Provided that in the case of renewal the applicant may apply for the renewal of the licence before its expiry or within one month of such expiry:
Provided further that the applicant may apply for renewal after the expiry of one month, but within three months of such expiry in which case the fee payable for renewal of such licence shall be rupees thirty plus an additional fee of rupees fifteen.
(ii) A fee of rupees seven and paise fifty shall be payable for a duplicate copy of a licence issued under this rule, if the original licence is defaced , damaged or lost.
154. Form of licence to manufacture Ayurvedic (including Siddha) or Unani drugs: (1) Subject to the conditions of rule 157 being fulfilled, a licence to manufacture for sale any Ayurvedic (including Siddha) or Unani drugs shall be issued in Form 25-D. The licence shall be issued within a period of three months from the date of receipt of the application. _______________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 376(E)dt 20.7.1978.
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(2) A licence under this rule shall be granted by the licensing authority after consulting such expert in Ayurvedic (including Siddha) or Unani Systems of medicine as the case may be, which the State Government may approve in this behalf.
1154-A Form of loan licence to manufacture for sale of Ayurvedic (including Siddha) or Unani drugs:—
A loan licence to manufacture for sale of any Ayurvedic (including Siddha) or Unani drugs shall be issued in Form 25E.
(2) A licence under this rule shall be granted by the Licensing Authority after consulting such expert in Ayurvedic (including Siddha) or Unani systems of medicine, as the case may be, which the State Government may approve in this behalf.
(3) The Licensing Authority shall, before the grant of a loan licence, satisfy himself that the manufacturing unit has adequate equipment, staff, capacity for manufacture and facilities for testing, to undertake the manufacture on behalf of the applicant for a loan licence.
155. Certificate of renewal—The certificate of renewal of a licence in Form 25-D shall be issued in Form 26-D.
1155-A. Certificate of renewal of a loan licence.—The certificate of renewal of a loan licence in Form 25-E shall be issued in Form 26-E.
2[155-B. Certificate of award of G.M.P. of Ayurveda, Siddha and Unani Drugs.- The certificate of Good Manufacturing Practices to manufacturers of Ayurveda, Siddha or Unani drugs shall be issued to licensees who comply with the requirements of Good Manufacturing Practice of Ayurveda, Siddha and Unani drugs as laid down in Schedule T.]
156. Duration of licence—An original licence in Form 25-D or a renewed in Form 26- D, unless sooner suspended or cancelled shall be valid upto the 31st December of the year following the year in which it is granted or renewed.
Provided that if the application for the renewal of a licence is made before its expiry or within one month of its expiry after payment of the additional fee of rupees thirty, the licence shall continue to be in force until orders are passed on the application. The licence shall be deemed to have expired, if the application for its renewal is not made within three months of its expiry.
______________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 376(E)dt 20.7.1978 2Ins. by G.O.I. Notification No. GSR 561(E)dt 23.6.2000.
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1156-A. Duration of loan licence—An original loan licence in Form 25-E or a renewed loan licence in Form 26-E, unless sooner suspended or cancelled, shall be valid up to the 31st December of the year following the year in which it is granted or renewed.
Provided that if the application for the renewal of a loan licence is made in accordance with rule 153-A, the loan licence shall continue to be in force until orders are passed on the application. The licence shall be deemed to have expired, if the application for its renewal is not made within three months of its expiry.
157. Conditions for the grant or renewal of a licence in Form 25-D—Before a licence in Form 25-D is granted or renewed in Form 26-D the following conditions shall be compiled with by the applicant, namely: — (1) The manufacture of Ayurvedic (including Siddha) or Unani drugs shall be carried out in such premises and under such hygienic conditions as are specified in Schedule T.
2[1-A for getting a certificate of ‘Good Manufacturing Practices’of Ayurveda Siddha- Unani drugs, the applicant shall made application on plain paper, providing the information on existing infrastructure of the manufacturing unit, and the licensing authority shall after verification of the requirements as per Schedule ‘T’ issue the certificate within a period of 3 months in form 26-E-I]..
(2) The manufacture of Ayurvedic (including Siddha) or Unani drugs shall be conducted under the direction and supervision of competent tec hnical staff consisting at least one person, who is a whole time employee and who possesses the following qualifications, namely—
(a) A degree in Ayurveda or Ayurvedic Pharmacy, Siddha or Unani system of medicine, as the case may be, conferred by a University, a State Government or Statutory Faculties, Councils and Boards of Indian Systems of medicines recognized by the Central Government or a State Government for this purpose, or
(b) A diploma in Ayurveda, Siddha or Unani system of medicine granted by a State Government for this purpose, or
(c) A graduate in Pharmacy or Pharmaceutical Chemistry or Chemistry or Botany of a University recognized by the Central Government with experience of at least two years in the manufacture of drugs pertaining to the Ayurvedic or Siddha or Unani systems of medicines, or
(d) A Vaid or Hakim registered in a State Register of Practitioners of indigenous systems of medicines having experience of at least four years in the manufacture of Ayurvedic or Siddha or Unani drugs, or ______________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 376(E)dt 20.7.1978 2Ins. by G.O.I. Notification No. GSR 561(E)dt 23.6.2000.
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(e) A qualification as Pharmacist in Ayurvedic (including Siddha) or Unani systems of medicines, possessing experience of not less than eight years in the manufacture of Ayurvedic or Siddha or Unani drugs as may be recognized by the Central Government.
(3) The competent technical staff to direct and supervise the manufacture of Ayurvedic drugs shall have qualifications in Ayurveda and the competent technical staff to direct and supervise the manufacture if Siddha drugs and Unani drugs shall have qualification in Siddha or Unani, as the case may be.
158. Conditions of licence.—A licence in Form 25-D shall be subject to the conditions stated therein and to the following further conditions, namely —
(a) The licensee shall maintain proper records of the details of manufacture and of the tests, if any, carried out by him, or by any other person on his behalf, of the raw material and finished products.
(b) The licensee shall allow an Inspector appointed under the Act to enter any premises where the manufacture of a substance in respect of which the licence is issued is carried on, to inspect the premises, to take samples of the raw material as well as finished products, and to inspect the records maintained under these rules.
1[(c) The licensee shall maintain an Inspection Book in form 35 to enable an Inspector to record his impressions and the defects noticed.]
2158-A Conditions of loan licence.—A licence in Form 25-E shall be subject to the conditions stated therein and to the following conditions, namely—
(a) The licence in Form 25-E shall be deemed to be cancelled or suspended, if the licence owned by the licensee in Form 25-D whose manufacturing facilities have been availed of by the licensee is cancelled or suspended, as the case may be, under these rules.
(b) The licensee shall comply with the provisions of the Act and of the Rules and with such further requirements if any, as may be specified in any Rules subsequently made under Chapter IV-A of the Act, provided that where such further, requirements are specified in the Rules; these would come into force four months after publication in the Official Gazette.
(c) The licensee shall maintain proper records of the details of manufacture and of the tests, if any, carried out by him, or any other person on his behalf, of the raw materials and finished products.
____________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 376(E)dt 20.7.1978 2Ins. by G.O.I. Notification No. GSR 561(E)dt 23.6.2000.
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(d) The licensee shall allow an Inspector appointed under the Act to inspect all registers and records maintained under these rules and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and the Rules have been observed.
1[(e) The licensee shall maintain an Inspection Book in form 35 to enable an Inspector to record his impressions and the defects noticed.
159. Cancellation and suspension of licences—(1) The Licensing Authority may, after giving an opportunity to show cause within a period which shall not be less than fifteen days from the date of receipt of such notice, why such an order should not be passed, by an order in writing stating the reasons therefore, cancel a licence issued under this Part or suspend it for such period as he thinks fit, either wholly or in respect of some of the drugs to which it relates, if in his opinion, the licensee has failed to comply with any of the conditions of the licence or with any provisions of the Act and the Rules made thereunder.
(2) A licensee whose licence has been suspended or cancelled may appeal to the State Government within a period of three months from the date of receipt of the order which shall, after considering the appeal, decide the same.
160. Identification of raw materials—Raw materials used in the preparation of Ayurvedic (including Siddha) or Unani drugs shall be identified and tested, wherever test are available for their genuineness, and records of such tests as are carried out for the purpose and the methods thereof shall be maintained.
2[PART XVI-A
APPROVAL OF INSTITUTIONS FOR CARRYING OUT TESTS ON AYURVEDIC, SIDDHA AND UNANI DRUGS
AND RAW MATERIALS USED IN THEIR MANUFACTURE ON BEHALF OF LICENSEES FOR MANUFACTURE FOR SALE OF AYURVEDIC, SIDDHA AND UNANI DRUGS.
160-A. Application for grant of approval for testing Ayurvedic, Siddha and Unani drugs. - Application for grant or renewal of approval for carrying out tests for identity, purity, quality and strength of Ayurvedic, Siddha and Unani drugs or the raw materials used in the manufacture thereof on behalf of licensees for manufacture for sale of the said Ayurvedic, Siddha and Unani drugs, shall be made in Form 47 to the Licensing Authority
______________________________________________________________________ 1Ins. by G.O.I. Notification No.GSR 331(E) dt 8.5.1984. 2Ins. by G.O.I. Notification No. GSR 701(E) dt 27.7.2001 and sub. By G.S.R.73(E) dt.31.01.2003.
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appointed by the State Government for the purposes of Part XVI, XVII or XVIII of these rules, as the case may be, and referred to as the ‘approving authority’ under this Part and shall be accompanied by an inspection fee of six thousand rupees in respect of the drugs specified in First Schedule to the Act.
Provided that the applicant shall furnish to the approving authority such additional information as may be required by it in connection with the application in Form 47.
Provided further that if the applicant applies for renewal of approval after is expiry but within six months of such expiry, the inspection fee payable shall be six thousand rupees plus an additional inspection fee at the rate of one thousand rupees per month in the case of testing of Ayurvedic, Siddha and Unani drugs specified in First Schedule to the Act.
Explanation. - For the purpose of this Part, the words “Ayurvedic, Siddha and Unani drugs” shall also mean and include the raw materials used in the manufacture of Ayurvedic, Siddha and Unani drugs, as the case may be.
160-B. Form in which approval to be granted for carrying out tests on Ayurvedic, Siddha and Unani drugs on behalf of licensees for manufacture of Ayurvedic, Siddha and Unani drugs and conditions for grant or renewal of such approval. - (1) Approval for carrying out such tests of identity, purity, quality and strength of Ayurvedic, Siddha and Unani drugs as may be required under the provisions of these rules, on behalf of licensee for manufacture of Ayurvedic, Siddha and Unani drugs shall be granted in Form 48.
(2) Before approval in Form 41 is granted or renewed, the following conditions shall be complied with by the applicants, namely: -
(i) The premises where the tests are carried out shall be well lighted and properly ventilated except where the nature of tests of any Ayurvedic, Siddha and Unani drug warrants otherwise. Wherever necessary, the premises shall be air-conditioned so as to maintain the accuracy and functioning of laboratory instruments or to enable the performance of special tests such as sterility tests and microbiological tests.
(ii) (a) The applicant shall provide adequate space having regard to the nature and number of samples of drugs proposed to be tested: Provided that the approving authority shall determine from time to time whether the space provided continues to be adequate.Provided further that separate section shall be provided for (i) Chemistry, (ii) Pharmacognosy, (iii) Ayurveda, Siddha and Unani, (iv) Microbiology, (v) Sample Room, (vi) Office-cum-Record Room with proper partitions and minimum required area is 800 sq. ft.
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(b) The applicant shall provide a list of persons who may be employed with him as experts, such as Chemist, Botanist and expert in Ayurveda/Siddha/Unani or Pharmacist who shall possess a degree in Chemistry, Botany, Ayurveda/Siddha/Unani/Bachelor in Pharmacy from a recognized University or equivalent, with experience for 2 years for carrying out tests or analysis as per the Ayurvedic, Siddha and Unani Pharmacopoeias.
(c) The applicant shall provide adequate equipments essesntial for carrying out tests for identity, purity, quality and strength of Ayurvedic, Siddha and Unani drugs as per pharmacopoeial standards or other available standards.
• List of equipment recommended is given below: Chemistry section. 1. Alcohol determination apparatus complete set. 2. volatile oil determination apparatus. 3. Boiling point determination apparatus 4. Melting point determination apparatus. 5. Refractometer. 6. Polarimeter. 7. Viscometer (Ostwalds, Red Viscometer.) 8. Tablet disintegration apparatus. 9. Moisture determination apparatus (IC filtrator.). 10. U.V.Spectro-photometer. 11. Muffle furnace. 12. Electronic Balance. 13. Hot air oven(s) different range of temperature/vacuum oven. 14. Refrigerator. 15. Glass distillation apparatus/plant. 16. Water supply demineralised exchange equipment/distillation equipment. 17. Air conditioner. 18. LPG Gas cylinder with burners. 19. Water bath(temperature controlled.) 20. Heating mantle(4) as required. 21. TLC apparatus with all accessories. 22. Sieves 10 to 120 wqith sieve shaker. 23. Centrifuge machine. 24. Dehumidifier. 25. pH meter. 26. G.L.C. with F.I.detector. 27. Silica crucible. 28. Tablet friability tester. 29. Tablet dissolution tester. 30. Other related equipment, reagents, glasswares etc. Pharmacognosy Section. 1. Microscope binocular. 2. Dissecting Microscope.
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3. Microtome. 4. Chemical balance. 5. Microslide cabinet. 6. Aluminium slide trays. 7. Hot air oven. 8. Occular Micrometer. 9. Stage Micrometer. 10. Camera Lucida Prism type and mirror type. 11. Hot plates. 12. Refrigerator. 13. LPG Cylinder with burners. 14. Other related equipments,reagents, glasswares etc. Note : Instuments like HPLC, HPTLC, atomic absorption Spectrophotometer
could be arranged by tie up with other laboratories. Microbiology section. 1. Laminar air flow bench(L.A.F.) 2. B.O.D. Incubator. 3. Plain Incubator. 4. Serological water bath. 5. Oven. 6. Autoclave/sterilizer. 7. Microscope (high power). 8. Colony counter. 9. Other related equipment and reagents.
(3). The applicant shall provide and maintain suitable equipment having regard to the nature and number of samples of Ayurvedic, Siddha and Unani drugs intended to be tested which shall be adequate in the opinion of the approving authority.
(4) The testing of Ayurvedic, Siddha and Unani drugs, as the case may be, for identity, purity, quality and strength shall be carried out under the active direction of one of the experts stated in clause (b) of sub-rule (2) who shall be the person-in-charge of testing and shall be held responsible for the reports of test issued by the applicant.
(5) The testing of Ayurvedic, Siddha and Unani drugs, as the case may be, for identity, purity, quality and strength shall be carried out by persons whose qualifications and experience of testing are adequate as stated in clause (b) of sub-rule (2).
(6) The applicant shall provide books of standard recognized under the provisions of the act and the rules made there under and such books of reference as may be required in connection with the testing of analysis of the products for the testing of which approval is applied for.
(7) The applicant shall provide list of standard Ayurvedic, Siddha and Unani drugs (Reference samples) recognized under the provisions of the Act and rules made thereunder and such reference samples kept in the laboratory may be required in connection with the testing or analysis of the products of which approval is applied for.
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160-C. Duration of approval. - An approval granted in Form 47 or renewed in Form 49 unless sooner suspended or withdrawn, shall be valid for a period of three years from the date on which it is granted or renewed.
Provided that if an application for the renewal of an approval in form 47 is made before its expiry or if the application is made within six months of its expiry after the payment of the additional inspection fee, the approval shall continue to be in force until orders to the contrary are passed on the application and approval shall be deemed to have expired if the application for renewal is not made within six months of expiry.
160-D. Conditions of approval. - An approval in Form 41 shall be subject to the following conditions, namely: -
I. The Institution granted approved under this Part (hereinafter referred to as the approved laboratory) shall provide and maintain adequate staff and adequate premises and equipment as specified in Rule 160-B.
II. The approved laboratory shall provide proper facilities for storage so as to preserve the properties of the samples to be tested by it.
III. The approved laboratory shall maintain records of tests for identity, purity, quality and strength carried out on all samples of Ayurvedic, Siddha and Unani drugs and the results thereof together with the protocols of tests showing the readings and calculation in such form as to be available for inspection and such records shall be retained in the case of substances for which date of expiry is assigned; for a period of two years from such date of expiry and in the case of other substances, for a period of three years.
IV. The approved laboratory shall allow the Inspector appointed under the Act to enter with or without prior notice the premises where testing is carried out and to inspect the premises and the equipment used for test and the testing procedures employed. The laboratory shall allow the Inspectors to inspect the registers and records maintained under these rules and shall supply to such Inspectors such information as they may require for the purpose of ascertaining whether the provisions of the Act and rules made thereunder have been observed.
V. The approved laboratory shall from time to time report to the approving authority any changes in the person-in-charge of testing of Ayurvedic, Siddha and Unani drugs or the expert staff responsible for testing, as the case may be, and any material alterations in the premises or changes in the equipment used for the purposes of testing which have been made since the date of last inspection made on behalf of the approving authority before the grant or renewal of approval.
VI. The approved laboratory shall furnish reports of the results of tests or analysis in Form 50.
VII. In case any sample of Ayurvedic, Siddha and Unani drug is found on test to be not of standard quality, the approved laboratory shall furnish to the approving authority
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and the licensing authority of the State where the manufacturer and/or sender of the Ayurvedic, Siddha and Unani drugs is located, a copy of the test report of the sample with the protocols of tests applied.
VIII. The approved laboratory shall comply with the provisions of the Act and rules made thereunder and with such further requirements, if any, as may be specified in the rules made from time to time under Chapter IV-A of the Act of which the approving authority has given the approved laboratory not less than four months’ notice.
IX. The approved laboratory shall maintain an inspection book to enable the Inspector to record his impression or defects noticed.
160-E. Inspection before grant of approval. - Before an approval in form 48 is granted, the approving authority shall cause the laboratory at which the testing of Ayurvedic, Siddha and Unani drugs as the case may be, is proposed to be carried out to be inspected jointly by the Inspectors appointed or designated by the Central Government and State Government for this purpose, who shall examine the premises and the equipment intended to be used for testing of drugs and verify into the professional qualifications of the expert staff who are or may be employed by the laboratory.
160-F. Report of inspection. - The Inspectors appointed by the Central Government as stated in Rule 160-E shall forward to the approving authority a detailed report of the results of the inspection.
160-G. Procedure of approving authority. - (1) If the approving authority after such further enquiry, if any, as it may consider necessary, is satisfied that the requirements of the rules made under the Act have been complied with and that the conditions of the approval and the rules made under the Act have been observed, it shall grant appro val in Form 48.
(2) If the approving authority is not satisfied, it shall reject the application and shall inform the applicant of the reasons for such rejection and of the conditions which shall be satisfied before approval could be granted.
160-H. Application after rejection. - If within a period of six months from the rejection of an application for approval, the applicant informs the approving authority that the conditions laid down have been satisfied and deposits inspection fee of two thousand rupees, the approving authority may, if, after causing a further inspection to be made and after being satisfied that the conditions for grant of approval have been complied, with grant the approval in Form 48.
160-I. Renewal. - On an application being made for renewal, the approving authority shall, after causing an inspection to be made and if satisfied that the conditions of the approval and the rules made under the Act have been complied with, shall issue a certificate of renewal in form 49.
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160-J. Withdrawal and suspension of approvals. - (1) The approving authority may, after giving the approved laboratory an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefore, withdraw an approval granted under this Part or suspend it for such period as it thinks fit either wholly or in respect of testing of some of the categories of Ayurvedic, Siddha and Unani drugs to which it relates, if in his opinion the approved laboratory had failed to comply with any of the conditions of the approval or with any provision of the Act or the rules made thereunder.
(2) Any approved laboratory, whose approval has been suspended or withdrawn, may, within three months of the date of the order of suspension or withdrawal, appeal to the State Government which shall dispose of the appeal in consultation with a panel of competent persons appointed by the Department of Indian Systems of Medicine & Homoeopathy, Government of India in this behalf and notified in the Offic ial Gazette.]
PART XVII—1[LABELLING, PACKING AND LIMIT OF ALCOHOL IN] AYURVEDIC (INCLUDING SIDDHA) OR UNANI DRUGS
1[161. Labelling, packing and limit of alcohol. ]—(1) There shall be considerably displayed on the label of the container or package of an Ayurvedic (including Siddha) or Unani drug, the true list of all the ingredients used in the manufacture of the preparation together with quantity of each of the ingredients incorporated therein and a reference to the method of preparation thereof as detailed in the standard text and Adikarana, as are prescribed in the authoritative books specified in the First Schedule to the Act:
Provided that if the list of ingredients contained in the medicine is large and cannot be accommodated on the label, the same may be printed separately and enclosed with packing and reference be made to this effect on the label.
(2) The container of a medicine for internal use made up ready for the treatment of human ailments shall, if it is made up from a substance specified in Schedule E (1), be labelled conspicuously with the words ‘Caution: To be taken under medical supervision’ both in English and Hindi language.
(3) Subject to the other provisions of these rules, the following particulars shall be either printed or written in indelible ink and shall appear in a conspicuous manner on the label of the innermost container of any Ayurvedic (including Siddha) or Unani drug and on any other covering in which the container is packed namely--
(i) The name of the drug. For this purpose the name shall be the same as mentioned in the authoritative books included in the Firs Schedule of the Act.
________________________________________________________________________ 1Ins. By G.O.I. Notification No. GSR 904(E) dt 2.11.1992.
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(ii) A correct statement of the net content in terms of weight, measure or number as the case may be. The weight and volume shall be expressed in metric system.
(iii) The name and address of the manufacturer. (iv) The number of the licence under which the drug is manufactured, the
figure representing the manufacturing licence number being preceded by the words ‘Manufacturing Licence Number’ or ‘Mfg. Lic. No.’ or ‘M.L.’.
(v) A distinctive batch number, that is to say, the number by reference to which details of manufacture of the particular batch from which the substance in the container is taken are recorded and are available for inspection, the figure representing the batch number being preceded by the words “Batch No.” or “Batch” or “Lot Number” or “Lot No.” or “Lot No.” or “Lot” or any distinguishing prefix.
(vi) The date of manufacture. For this purpose the date of manufacture shall be the date of completion of the final products, or the date of bottling or packing for issue.
(vii) The words “Ayurvedic medicine” or “Siddha medicine” or “Unani medicine” as the case may be.
(viii) The words “FOR EXTERNAL USE ONLY” if the medicine is for external application.
(ix) Every drug intended for distribution to the medical profession, as a free sample shall, while complying with the labelling provisions under clauses (i) to (viii), further bear on the label of the container the words “Physicians sample. Not to be sold” which shall be over-printed.
1[ix (a) Preparation (Asavas) with high content of alcohol as base
Name of the drug Maximum size of packing (i) Karpur Asava 15 ml
(ii) Ahiphensava 15 ml
(iii) Mrgamadasava 15 ml
(ix (b) Preparations containing self-generated alcohol
Name of the drug Maximum content of alcohol (Ethyl alcohol v/v)
Maximum size of packing
(i) Mritsanjivani Sura
(ii) Mahadrakshasava
16 per cent
16 per cent
30 ml.
120 ml.]
_______________________________________________________________________ 1Ins. By G.O.I. Notification No. GSR 904(E) dt 2.11.1992.
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(4) Nothing in these rules shall be deemed to require the labelling of any transparent cover or of any wrapper case or other covering used solely for the purpose of packing, transport or delivery.
1[161-A. Exemption in labeling and packing, provisions for export of Ayurvedic (including Siddha) and Unani drugs.- (1) Labels and packages or containers of Ayurvedic, Siddha and Unani drugs for export may be adapted to meet the specific requirements of the law of the country to which the said drug is to be exported, but the following particulars shall appear in conspicuous position on the container in which drug is packed and on every other covering in which that container is packed, namely :
(a) Name of the Ayurvedic, Siddha and Unani drug (Single or compound formulations;
(b) the name, address of the manufacturer and the number of licence under which the drug has been manufactured;
(c) batch or lot number; (d) date of manufacture, along with the date for “Best for use before”; (e) main ingredients, if required by the import country; (f) for export;
Provided that where Ayurvedic, Siddha and Unani Single or compound drug not classified under First Schedule or Schedule E-(I), is required by the consignee to be not labeled with the name and address of the manufacturer, the labels on packages or containers shall bear a code number as approved by the Licensing Authority menti9oned in Rule 152.
(2) the provisions of Rule 161 shall not apply to a medicine made up “ready for treatment”, whether after, or without, alteration, which is supplied on the prescription of a registered medical practitioner if the medicine is labeled with the following particulars, namely:-
(a) the name and address of the suppliers; (b) the words “For External Use Only”, if the medicine is for external application.]
PART XVIII-GOVERNMENT ANALYSIS AND INSPECTORS FOR AYURVEDIC (INCLUDING SIDDHA) OR UNANI DRUGS
162. Duties of Inspectors specially authorised to inspect the manufacture of Ayurvedic (including Siddha) or Unani drugs—Subject to the instructions of the controlling authority, it shall be the duty of an Inspector authorised to inspect the manufacture of Ayurvedic (including Siddha) or Unani drugs— ________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 787(E) dt 17.10.2000
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(i) to inspect not less than twice a tear, all premises licensed for manufacture of Ayurvedic (including Siddha) or Unani drugs within the area allotted to him and to satisfy himself that the conditions of the licence and the provisions of the Act and the Rules made thereunder are being observed;
(iii) to take samples of the drugs manufactured on the premises and send them for test or analysis in accordance with these Rules;
(iv) to institute prosecutions in respect of violation of the Act and the Rules made thereunder.
1[162A-Qualification of the State Drug Licensing Authority for Licensing of Ayurvdeda,Siddha and Unani drugs:
(a) The Ayurvedic/ siddha/ Unani qualifications as per Schedule II of CCIM Act 1970/ B Pharma (Ayurveda0 of a recognized University.
(b) At least 5 years experience in the Ayurveda/ Siddha/ Unani drug manufacturing or testing of Ayurvedic, siddha and Unani drugs or enforcement of provisions of Chapter IVA of the Drugs and Cosmetics Act,1940 and Rules made there under or teaching/ research on clinical practice of Ayurveda/ siddha/ Unani System.]
163. Procedure for despatch of sample to Government Analyst and to receipt by the Government Analyst—(1) Sample for test or analysis shall be sent to the Government Analyst by registered post or by hand in a sealed package, enclosed together with a memorandum in Form 18-A in an outer addressed to the Government Analyst.
(2) The package as well as the outer cover shall be marked with a distinguishing number.
(3) A copy of the memorandum and a specimen impression of the seal used to seal the package shall be sent by registered post or by hand to the Government Analyst.
(4) On the receipt of the package from an Inspecto r, the Government Analyst or an Officer authorised by him in writing in his behalf shall open the package and shall also record the conditions of the seals on the package.
(5) After the test or analysis has been completed, one copy of the results of the test or analysis shall be supplied forthwith to the sender in Form 13-A shall also be sent simultaneously to the Controlling Authority and to the Drugs Controller, India.
164. Method of test or analysis to be employed in relation to Ayurvedic (including Siddha) or Unani drugs.—The method of test or analysis to be employed in relation to an Ayurvedic (including Siddha) or Unani drug shall be such as may be specified in the Ayurvedic (including Siddha) or Unani Pharmacopoeia, or if no such pharmacopoeias, ________________________________________________________________________ Ins. by G.O.I.Notification No G.S.R.76(E) dt03.02.2003.
206
such tests as the Government Analyst may employ, such tests being scientifically established to determine whether the drug contains the ingredients as stated on the label.
165. Qualifications of Government Analyst. —A person who is appointed a Government Analyst under section 33 F of the Act shall be a person possessing the qualifications prescribed in rule 44 or a degree in Ayurveda, Siddha or Unani System, as the case may be, conferred by a University, a State Government or Statitory Faculties, Councils and Boards of Indian Systems of Medicine recognized by the Central or State Government, as the case may be, for this purpose and has had not less than three years’ post graduate experience in the analysis of drugs in a laboratory under the control of (i) a Government Analyst appointed under the Act, or (ii) a Chemical Examiner to Government, or (iii) the Head of an institution specially approved for the purpose by the appointing authority.
166. Duties of Government Analyst—(1) The Government Analyst shall analyze or test or cause to be analyzed or tested such samples of Ayurvedic (including Siddha) or Unani drugs as may be sent to him by Inspectors or any other persons or authority authorised by the Central Government or State Government under the provisions of Chapter IV A of the Act and shall furnish reports of the results of test or analysis in accordance with these rules.
(2) A Government Analyst appointed under Section 33F shall from time to time forward to the Government reports giving the result of analytical work and research with a view to their publications at the discretion of the Government.
1167. Qualifications of Inspector—A person who is appointed an Inspector under section 33G shall be a person who—
(a) has the qualifications laid down under rule 49 and shall have undergone practical training in the manufacture of Ayurvedic (including Siddha) or Unani drug, as the case may be; or
(b) has a degree in Ayurvedic or Siddha or Unani System or a degree in Ayurveda Pharmacy, as the case may be, conferred by a University or State Government or a Statutory Faculty, Council or Board of Indian Systems of Medicine recognized by the Central Government or the State Government for this purpose; or
(c) has a diploma in Ayurveda, Siddha or Unani Systems, as the case may be, granted by a State Government or an Institution recognized by the Central Government or a State Government for this purpose.
________________________________________________________________________ 1 Amended by G.O.I. Notification No. GSR 376 dt 27.7.1978.
207
1[PART XIX STANDARDS OF AYURVEDIC, SIDDHA AND UNANI DRUGS
168. Standards to be complied with in manufacture for sale or for distribution of Ayurvedic, Siddha and Unani Drugs. -
Class of Drugs Standards to be complied with 1.
2.
Single drugs included in Ayurvedic Pharmacopoeia.
Asavas and Arishtas
The standards for identity, purity and strength as given in the editions of Ayurvedic Pharmacopoeia of India for the time being in force.
The upper limit of alcohol as self generated alcohol should not exceed 12% v/v excepting those that are otherwise notified by the Central government from time to time.]
_______________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 519(E) dt 26.6.1995.
208
SCHEDULE A FORM 1
[See Rule 4] Memorandum to the Central Drugs Laboratory
Serial Number……………………..
To the Director, Central Drugs Laboratory………………………………….
From………………………..
I send herewith, under the provisions of Section 25 (4) of the Drugs and Cosmetics Act, 1940, sample(s) of a drug purporting to be……………for test or analysis and request that a report that a report of the result of the test or analysis may be supplied to this Court.
1. The distinguishing number on the packet is ……………………………… 2. Particulars of offence alleged……………………………………………. 3. Matter on which opinion is required…………………………… 4. A fee of Rs……………..has been deposited in Court.
Date……………. ………………… Magistrate
_________________
FORM 2
[See Rule 6]
Certificate of test or analysis by the Central Drugs Laboratory
Certified that the sample bearing number………………………….. Purporting to be a separate to be a sample of. ……………received on…………… with memorandum No. …………………………………….dated……………………… from ………………………………has been tested / analysed and that the result of such test / analysis is as stated below.
2. The conditions of the seals on the packet on receipt was as follows: —
*3. In the opinion of the undersigned the sample is of standard quality as defined in the is not of standard quality as defined in
Drugs and Cosmetics Act, 1940 and Rules thereunder for the reasons given below: the Drugs and Cosmetics Act, 1940, and Rules thereunder
209
Date…………… Director Central Drugs Laboratory or other authorised officer
Details of results of test or analysis with protocols of test applied
Date………….. Director Central Drugs Laboratory or other authorised officer
* If opinion is required on any other matter, the paragraph should be suitably amended.
_____________________
1Form 3 to 7
______________________
2FORM 8
(See Rule 24)
Application for licence to import drugs (excluding those specified in Schedule X) to the Drugs and Cosmetics Rules 1945.
I/We* ………………………………………….. (full address with telephone number, fax number and e-mail address) hereby apply for a licence to import drugs specified below manufactured by M/s ………………………………(full address with telephone no, fax and e- mail no.).
2. Names of the drugs to be imported:
(1) (2) (3)
3. I/We* …………………………………. enclose herewith an undertaking in Form 9 dated………. signed by the manufacturer as required by rule 24 of the Drugs and Cosmetics Rules, 1945.
4. I/We …………………………………. enclose herewith a copy of Registration Certificate concerning the drugs to be imported in India, issued under Form 41 of the rules, vide Registration Certificate No. …………dated ………….. issued through M/s. .………………….(name and full address)……………………valid up to …………………..
210
5. I/We* ……………………………….. hold a valid wholesale licence for sale or distribution of drugs or valid licence to manufacture drugs, under the provisions of the Act and rules made thereunder. A copy of the said licence is enclosed.
6. A fee of ………….. has been credited to Government under the Head of Account “0210 – Medical and Public Health, 04-Public Health, 104-Fees and Fines” under the Drugs and Cosmetics Rules 1945 – Central vide Challan No. ……………… dated ……….. (attached in original)
Signature ………………..
Name ………………..
Designation …………
Seal/Stamp of Manufacturer’s agent in India
Place …….. Date ……….. ___________________________________________________________________________ 1Omitted under Government of India Notification No. F. 1-16/57-D, dated 15-6-1957. 2Subs. by G.O.I. Notification No. GSR 604(E) dt 24.8.2001. *delete whichever is not applicable.
FORM 8-A
[See rule 24)
Application for licence to import drugs specified in Schedule X to the Drugs and Cosmetic Rules 1945.
I/We* ……………………………(full address with telephone number, fax number and e-mail address) hereby apply for a licence to import drugs specified below manufactured by M/s………………………… (full address with telephone No, fax and e-mail No.).
2. Name of the drugs to be imported.
(1) (2) (3)
3. I/We* ………………………… enclose herewith an undertaking in Form 9 dated ………… signed by the manufacturer as required by rule 24 of the Drugs and Cosmetics Rules, 1945.
4. I/We* ………………………….. enclose herewith a copy of Registration Certificate concerning the drugs to be imported in India, issued under Form 41 of the rules, vide Registration Certificate No. …………. dated ………………. issued through M/s. ……………………….(name and full address) ………..……….. valid upto …………………
211
5 I/We* ………………. Hold a valid wholesale licence for sale or distribution of drugs or licence to manufacture drugs, under the provisions of the Act and rules made thereunder. A copy of the said licence is enclosed.
6. A fee of ……………….. has been credited to Government under the Head of Account “0210 – Medical and Public Health, 04- Public Health, 104- Fees and Fines” under the Drugs and Cosmetics Rules 1945 – Central vide Challan No. ……. dated ……….. ( attached in original).
Signature ………………..
Name ………………..
Designation …………
Seal/Stamp of Manufacturer’s agent in India
Place …….. Date ………..
FORM 9
[See Rule 24]
Form of undertaking to accompany an application for an import licence
Whereas …………………… of ………………… intends to apply for a licence under the Drugs & Cosmetics Rules, 1945, for the import into India, of the drugs specified below manufactured by us, we ………………… of …………………. hereby give this undertaking that for the duration of the said licence—
(1) the said applicant shall be our agent for the import of drugs into India;
(2) we shall comply with the conditions imposed on a licence by 1[Rules 74 and 78]of the Drugs & Cosmetics Rules, 1945;
(3) we declare that we are carrying on the manufacture of the drugs mentioned in this undertaking at the premises specified below, and we shall from time to time report any change of premises on which manufacture will be carried on and in cases where manufacture is carried on in more than one factory any change in the distribution of functions between the factories;
(4) we shall comply with the provisions of Part IX of the Drugs & Cosmetics Rules, 1945;
___________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. * delete whichever is not applicable.
212
(5) every drug, manufactured by us for import under licence into India shall as regards strength, quality and purity conform with the provisions of Chapter III of the Drugs & Cosmetics Act, 1940, and the Drugs & Cosmetics Rules, 1945;
(6) we shall comply with such further requirements, if any, as may be specified by Rules, by the Central Government under the Act and of which the licensing authority has given to the licensee not less than four months’ notice.
Names of drugs and classes of drugs
Particulars of premises where manufacture is carried on.
Date………….. 1[Signature, Name, Designation Seal/Stamp of manufacturer or on behalf of the manufacturer]
1[FORM 10 [See rules 23 and 27]
Licence to import drugs (excluding hose specified in Schedule X) to the Drugs and Cosmetic Rules, 1945.
Licence Number ………………. Date ……………
………………………………………………………… (Name and full address of the Importer) is hereby licensed to import into India during the period for which the licence is in force, the drugs specified below, manufactured by M/s. ……………………………. (name and full address) and any other drugs manufactured the said manufacturer as may from time to time be endorsed on this licence.
2. This licence shall be valid in force from …………. to ……… unless it is sooner suspended or cancelled under the said rules.
3. Names of drugs to be imported.
Place :
Date : LICENSING AUTHORITY Seal/Stamp
* Delete whichever is not applicable.
____________________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 604(E) dt 24.8.2001.
213
Conditions of Licence.
1. A photocopy of licence shall be displayed in a prominent place in a part of the premises, and the original licence shall be produced, whenever required.
2. Each batch of drug imported into India shall be accompanied with a detailed batch test report and a batch release certificate, duly signed and authenticated by the manufacturer with date of testing, date of release and the date of forwarding such reports. The imported batch of each drug shall be subjected to examination and testing as the licensing authority deems fit prior to its marketing.
3. The licensee shall be responsible for the business activities of the manufacturer in India along with the registration holder and his authorized agent.
4. The licensee shall inform the licensing authority forthwith in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the licensing authority in the name of the firm with the changed constitution.
.
FORM 10-A (See rule 23 and 27)
Licence to import drugs specified in Schedule X to the Drugs and Cosmetic Rules, 1945.
Licence Number ……………………….. Date ………………….
……………………………………………………………………….. (Name and full address of the importer) is hereby licenced to import into India during the period for which the licence is in force, the drugs specified below, manufactured by M/s. ……………………… (name and full address) and any other drugs manufactured by the said manufacturer as may from time to time be endorsed on this licence.
2. This licence shall be in force from ………………… to ………………. unless it is sooner suspended or cancelled under the said rules.
3. Names of drugs to be imported.
Place: ………… Date : …………
LICENSING AUTHORITY Seal/Stamp.
* Delete whichever is not applicable.
214
Conditions of Licence.
1. A photocopy of licence shall be displayed in a prominent place in a part of the premises, and the original licence shall be produced, whenever required.
2. Each batch of drug imported into India shall be accompanied with a detailed batch test report and a batch release certificate, duly signed and authenticated by the manufacturer with date of testing, date of release and the date of forwarding such reports. The imported batch of each drug shall be subjected to examination and testing as the licensing authority deems fit prior to its marketing.
3. The licencee shall be responsible for the business activities of the manufacturer in India along with the registration holder and his authorized agent.
4. The licencee shall inform the licensing authority forthwith in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the licensing authority in the name of the firm with the changed constitution.]
FORM 11 [See Rule 33]
Licence to import drugs for the purposes of examination, test or analysis
I…………………….of……………….is hereby licensed to import from……………………the drugs specified below for the purposes of examination, test or analysis at ……………………or in such other places as the licensing authority may from time to time authorize.
2. This licence is subject to the conditions prescribed in the Rule under the Drugs & Cosmetics Act, 1940.
3. This licence shall, unless previously suspended or revoked, be in force for a period of one year from the date specified below—
Names of drugs Quantity which may be imported
Date…………………. Licensing Authority
215
____________________
1[FORM 11 – A
(See rule 33-A)
Licence to import drugs by a Government Hospital or Autonomous Medical Institution for the treatment of patients.
Licence No. ……………… Date ………….
Dr. ……………………………………. Designation ……………………………………. of ………………………………….(Name of College/Hospital/Autonomous Institution) is hereby licenced to import from M/s. …………………………..(name and full address) the drugs specified below for the purpose of treatment of patients for the disease (name of the disease) ……………. at ………………… or in such other places as the licensing authority may from time to time authorize.
2. This licence shall, unless previously suspended or revoked, be in force for a period of one year form the date of issue specified above.
3. Name of drugs to be imported:
Names of drugs Quantity which may be imported
Place :……….. Date : ………. Licensing Authority
Seal / Stamp
_______________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 604(E) dt 24.8.2001
216
Conditions of Licence
1. The licence shall be displayed in the Office of the Medical Superintendent of government Hospital / Head of Institution of Autonomous Medical Institution.
2. The licensee shall store the drugs imported under this licence under proper storage conditions.
3. The drugs imported under this licence shall be exclusively used for the treatment of patients, and a record shall be maintained in this regard, by a registered pharmacist giving the full name(s) and address(es) of the patients , diagnosis, dosage schedule, total quantity of drugs imported and issued, and shall be countersigned by the Medical Superintendent of the Government Hospital or Head of the Autonomous Medical Institution which shall be produced, on demand by an Inspector appointed under the Act.]
FORM 12
[See Rule 34]
Application for licence to import drugs for purpose of examination, test or analysis
I ………………………………..resident of …………………………………by occupation ……………….hereby apply for a licence to import the drugs specified below for the purposes of examination, test or analysis at………………….from………………..and I undertake to comply with the conditions applicable to the licence.
1[A fee of rupees…………… has been credited to Government under the head of Account ‘0210-Medical and Public Health, 04-Public Health, 104-Fees and Fines under the Drugs and Cosmetics Rules, 1945—Central vide Challan No……. dated…… (attached in original).]
Names of drugs and classes of drugs Quantities
Date…………… Signature…………………
__________________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 604(E) dt 24.8.2001
217
1FORM 12-A
[See Rule 36, second proviso]
Application for the issue of a permit to import small quantities of drugs for personal use
I ………………………..resident of ……………………………………….by occupation……………………………….hereby apply for a permit to import the drugs specified below for personal use from……………………………………………
I attach a prescription from a registered medical practitioner in regard to the need for the said drugs.
Names of drugs Quantities
Date…………………… Signature…………………
2 [FORM 12-AA (See rule 34A)
Application for licence to import small quantities of new drugs by a Government Hospital or Autonomous Medical Institution for the treatment of patients.
I, ………………… (name and designation) ………………………………….. of ………… …………… (name of the Hospital/Autonomous Medical Institution) hereby apply for a licence to import small quantities of new drugs specified below for the purpose of treatment of patients for the disease ………………. (name of the disease) at ……………….. (name and place of the hospital) and I undertake to comply with the conditions applicable to the licence and other provisions of the Drugs and Cosmetics Act, 1940 and the rules made thereunder from time to time.
A fee of rupees ……………………… has been credited to Government under the Head of Account “0210-Medical and Public Health, 04- Medical and Public Health, 10- Fees and Fines” under the Drugs and Cosmetics Rules, 1945 – Central vide Challan No……….. dated ………… (attached in original).
2. Name of new drugs to be imported:
_____________________________________________________________________ 1Added under Government of India Notification No. F. 1-36/54-DS, dated 3-3-1955. 2Subs. by G.O.I. Notification No. GSR 604(E) dt 24.8.2001
218
Names of drugs Quantity which may be imported
Place: ………… Date : …………
Signature ………………………. Name …………………………. Seal / Stamp ………………….
CERTIFICATE
Certified that the drugs specified above for import are urgently required for the treatment of patients suffering from………………………….. and that the said drug(s) is/are not available in India.
Signature …………………. Place : ……….. Medical Superintendent of the Government of Hospital / Head of Date: ………… Autonomous Medical Institution
Seal / Stamp
FORM 12-B [See Rule 36, second proviso]
Permit for the import of small quantities of drugs for personal use
……………………………….of ………………………….is hereby permitted to import from………………………….the drugs specified below for personal use.
2. This permit is subject to the conditions prescribed in the Rules under the Drugs and Cosmetics Act, 1940.
3. This permit shall, unless previously suspended or revoked, be in force for a period of six months from date specified below.
Names of drugs Quantities, which may be imported.
Date……………………… Licensing Authority
________________
219
FORM 13 [See Rule 46]
Certificate of test or analysis by Government Analyst under Section 25 (1) of the Drugs and Cosmetics act, 1940
1. Name of Inspector from whom received……………
2. Serial No. and date of Inspector’s memorandum ………..
3. Number of sample…………………………
4. Date of receipt ………………
5. Name of drugs purporting to be contained in the sample ……….
6. Condition of seals on the 1[packet or on portion of sample or container] ……….
7. Result of test or analysis with protocols of test or analysis applied …………
In the opinion of the undersigned the sample referred to above
is of standard quality as defined in the Drugs and Cosmetics Act, 1940. and Rules thereunder is not of standard quality as defined in the Drugs and Cosmetics Act 1940 and Rules thereunder
for the reasons given below:-
Date…………… Government Analyst…………..
_______________
2FORM 13-A [See Rule 163 (5)]
Certificates of tests or analyst by Government Analyst under Section 33H of the Drugs and Cosmetics Act, 1940
1. Names of Inspector from whom received……………………….. 2. Serial No. and date of Inspector’s memorandum………………….. 3. Number of sample………………………………………………… 4. Date of receipt…………………………………. 5. Names of drugs purporting to be contained in the sample……………. 6.Condition of seals on the package…………………………………….. 7.Result of test or analysis with protocols of test or analysis applied
…………………………………………………….
Date…………… Government Analyst………….. ____________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 59(E) dt 7.2.1995. 2Added under G.O.I. Notification No. F 1-23/67-D, dated 2-2-1970.
220
FORM 14-A [See Rule 47]
Application from a purchaser for test or analysis of a drug under Section 26 of the Drugs and Cosmetics Act, 1940
1. Full name and address of the applicant……………………………………….
2. Occupation…………………………………….
3. Name of drug purporting to be contained in the sample………………………
4. Name and full address of the pharmacy or concern where the drug was purchased .
5. Date on which purchased……………………………………………..
6. Reasons why the drug is being submitted for test or analysis .…..…………………………………………………………………………
17. A fee of rupees …………………………………..vide Schedule B of the Drugs and Cosmetics Rules, 1945, has been credited to Government under the head of account “080— Medical—Miscellaneous—Fees under the Drugs and Cosmetics Rules, 1945— Central/State”—vide treasury receipt attached.
I hereby declare that the drug being submitted for test was purchased by or for me. I further declare that the sample of the drug being sent for test or analysis is exactly as it was purchased and has not been tampered with in any way to reduce its potency.
Date………………….. Signed…………
______________
FORM 14-B [See Rule 47]
Certificate of test or analysis by Government Analyst under Section 26 of the Drugs and Cosmetics Act, 1940
1. Name of person from whom sample received………………………. 2. Date of receipt……………………………………………………… 3. Name of drug purporting to be contained in the sample…………………..
____________________________________________________________________ 1Added under Government of India Notification No. F. 1-3/51-D.S., dated 15-10-1954.
221
4. Opinion of the Government Analyst—The sample referred to above is / is not of standard quality as defined in the Drugs and Cosmetics Act, 1940 and Rules hereunder.
Date…………… Government Analyst…………..
_______________
1FORM 15 [See Rule 54 and 145 C]
Order under Section 22 (1)(c) of the Drugs and Cosmetics Act, 1940 requiring a person not to dispose of stock in this possession
Whereas, I have reasons to believe that the stocks of drugs / cosmetics in your possession, detailed below contravene the provisions of section 18 of the Drugs and Cosmetic s Act, 1940;
Now, therefore, I hereby require you under clause (c) of sub-section (1) of section 22 of the said Act not to dispose of the said stock for a period of ………….days from the date of this order.
Date……………. Inspector……………….
Details of stock of drugs/ cosmetics
Date………………… Inspector……………….
------------------------------
2FORM 16 [See Rule 55 and 145-B]
Receipt for stock of drugs or cosmetics or for record, register documents or material object seized under section 22 (1) (c) or (cc) of the Drugs and Cosmetics Act, 1940.
The stock of drugs or cosmetics or records, registers, documents or material objects detailed below has / have this day been seized by me under the provisions of clause (c) or clause (cc) of sub-section (1) of section 22 of the Drugs and Cosmetics Act. 1940 (23 of 1940) from the premises of ……………………………situated at …………………………..
Date………………. Inspector……………….
Details of drugs, cosmetics, records, registers, documents or material object seized
Date………………… Inspector………………...
___________________________________________________________________ 1Amended by G.O.I. Notification No. G.S.R.1594, dtd 13-11-1976. 2Amended by G.O.I. Notification No. G.S.R. 926 dtd 16-07-1977.
222
1FORM 17 [See Rules 56 and 145-A]
Intimation to person from whom sample is taken
To…………………..
I have this day taken from the premises of ……………………..situated at……………………………samples of the drugs / cosmetics specified below for the purpose of test or analysis.
Date………………. Inspector……………….
Details of samples taken
Date………………. Inspector………………..
______________
2[FORM 17-A
I[See Rules 56-A and 145-AA]
Receipt for samples of drugs or cosmetics taken where fair price tendered thereof under sub- section (I) of Section 23 of the Drugs and Cosmetics Act, 1940 is refused.
To …………………….. ……………………..
Whereas I, this ……… day of …….19 …….. have taken, from the premises of situated at …………… samples of drugs/cosmetics as specified below:-
Details of Samples …………..
And where I had offered to pay you rupees……………….. as the fair price of the samples of drugs/cosmetics taken:
And whereas, you have refused to accept the fair price tendered thereof.
Now, therefore, I give you the receipt as the fair price tendered for the samples of the drugs/cosmetics taken by me.
Date: ……………. Inspector …………….]
__________________________________________________________________________ 1Added under G.O.I.Notification No. F 1-23/67-D, dated 2-2-1970. 2 Ins. by G.O.I. Notification No. GSR 292(E) dt 29.5.1977.
223
FORM 18 [See Rule 57]
Memorandum to Government Analyst
Serial No. of Memorandum…………………………………………………
From To
The Government Analyst
The portion of sample / container described below is sent herewith for test or analysis under the provisions of clause (i) of sub-section (4) of Section 23 of the Drugs and Cosmetics Act, 1940.
The portion of sample / container has been marked by me with the following mark.
Details of portion of sample or container with 1[name of drug/cosmetic] which it purports to contain—
Date……………. Inspector……….…….
________________
2FORM 18-A [See Rule 163 (1)]
Memorandum to Government Analyst Serial No. From To
The Government Analyst
The portion of sample / container described below is sent herewith for test or analysis under the provisions of Section 33H of the Drugs and Cosmetics Act. 1940.
The portion of sample / container has been marked by me with the following mark.
Details of portion of sample or container with name of ingredients from which it is claimed to be made.
Date………………. Inspector……………….. ____________________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 370(E) dt 7.4.1994. 2Amended by G.O.I. Notification No. S.O. 2139 dt 12-8-1972.
224
1FORM 19 [See Rule 59 (2)]
Application for grant or renewal of a2[licence to sell, stock or exhibit or offer for sale, or distribute] drugs other than those specified in Schedule X.
1. I / We ……………………hereby apply for licence to sell by wholsesale/retail drugs specified in Schedules C and C(1) excluding those specified in Schedule X *and/or drugs other than those specified in Schedules C, C(1) and X to the Drugs and Cosmetics Rules, 1945 *and also to operate a pharmacy on the premises situated at ………………………………….
2. ? The sale and dispensing of drugs will be made under the personal supervision of the qualified persons namely:-
……………………………… (Name) …………………….. (Qualification) ……………………………… (Name) …………………….. (Qualification)
3. Categories of drugs to be sold…………………………………………….. 4.O Particulars of special storage accommodation ………………………………….. 5. A fee of rupees………………….has been credited to Government under the head of
account………………………………………………
Date………………………… Signature………………..]
* Delete whichever is not applicable. ? To be deleted if drugs will be sold only by wholesale. O Required only if products requiring special storage are to be sold.
______________
FORM 19-A [See Rule 59 (2)]
Application for the grant or renewal of a restricted 2[licence to sell, stock or exhibit for sale, or offer for sale or distribute] drugs by retail by3[* * *] dealers who do not engage the
services of a qualified person
1. I / We ………………………….of………………………………..hereby Drugs other than those specified
apply for a licence to sell by retail (i) in Schedule C, C1 and X_______ 3[* * * ]
on the premises situated at……………………………………
_____________________________________________________________________ 1Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982. 2 Subs. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985. 3Omitted by G.O.I. Notification No. GSR 231(E) dt 4.6.1996. .
225
or (ii) 1[Drugs specified in Schedule C(1)] on the premises situated [Drugs specified in Schedule C(1)] as vendor in the
at……………………………………… __________________________________ area……………………………………….
2. Sales shall be restricted to such drugs as can be sold without the supervision of a qualified person under the Drugs and Cosmetics Rules.
3. Names or classes of drugs proposed to be sold……………………………..
*4. Particulars of the storage accommodation for the storage of 1[Schedules C(1)] on the premises referred to above.
**5. The drugs for sale will be purchased from the following dealers and such other dealers as may be endorsed on the licence by the Licensing Authority from time to time.
Name of dealers………………………………….Licence No. ……………………..
2[* * *] 6. A fee of rupees ___________has been credited to Government under the
twenty head of account……………………………………………………………………..
Date…………………… Signature……………….
*Delete whichever is not required. **Applies only to an itinerant vendor.
3FORM 19-AA [See Rule 62C]
Application for grant or renewal of a4[ licence to sell, stock or exhibit or offer for sale by wholesale or to distribute] drugs from a motor vehicle
1. I / We __________________________________of _________________hereby apply for 4[licence to sell, stock or exhibit or offer for sale by wholesale or to distribute] drugs specified in Schedule C and C (1) and /or drugs other than those specified in Schedule C and C (1) from the vehicle bearing registration no._______________ assigned under the Motor Vehicles Act, 1939.
2. Categories of drugs to b e sold / distributed_________________________ ___________________________________________________________________________ 1Subs. by G.O.I. Notification No.GSR 487(E) dt 2.7.1984. 2Omitted by G.O.I. Notification No. GSR 231(E) dt 4.6.1996. 3Ins. by G.O.I. Notification No.X.11013/7/76-D&MS dt 25.1.1979. 4Subs. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985.
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3. A fee of rupees________________________ has been credited to Government under the head of account_________________________________
*4. Particulars of the storage accommodation for the storage of drugs specified in Schedules C and C (1) on the vehicle referred to above.
Date______________________ Signature_____________
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FORM 19-B [See Rule 67-A]
Application for 1[licence to sell, stock or exhibit for sale, or offer for sale or distribute] Homoeopathic medicines
1. I / We ………………………of…………………….hereby apply for a licence to sell by *[wholesale / retail] Homoeopathic medicines on the premises situated at……………………..
**2. The sale and dispensing of Homoeopathic medicines shall be made under the personal supervision of the following competent person in -charge.
Name………………………
3. A fee of rupees ………………has been credited to Government under the head of account…………………………………..
Date………………. Signature………………
*Delete whichever is not required. ** To be deleted if Homoeopathic medicines will be sold by wholesale.
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2[FORM 19-C [See Rule 59(2)]
Application for grant or renewal of a1[licence to sell, stock, exhibit or offer for sale, or distribute] drugs specified in Schedule X.
1. I/We …………………………. of ………………….. hereby apply for a licence to sell by *wholesale/retail drugs specified in Schedule X to the Drugs and Cosmetics Rules, 1945. We operate a pharmacy on the premises, situated at ……………. __________________________________________________________________________ 1 Subs. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985 2 Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982
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2. ** The sale and dispensing of drugs will be made under the personal supervision of the qualified persons mentioned below:-
……………………………… (Name) …………………….. (Qualification) ……………………………… (Name) …………………….. (Qualification) 3. Names of drugs to be sold.
4. # Particulars of storage accommodation.
5. A fee of rupees ……………………….. has been credited to Government account under the head of account………………………
Date…………. Signature …………………..]
* Delete whichever is not applicable. ** To be deleted if drugs will be sold only by whole. # Required only if products requiring special storage are to be sold.
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FORM 20 [See rule 61 (1)]
1[Licence to sell, stock or exhibit or offer for sale, or distribute] drugs by retail other than those specified in 2[Schedules C, C(1) and X].
I ……………………………….is hereby 1[licensed to sell, stock or exhibit or offer for sale or distribute] by retail drugs other than those specified in 2[Schedules C,C (1) and X] of the Drugs and Cosmetics Rules 1945, *and to operate a pharmacy on the premises situated at………………..subject to the conditions specified below and to provisions of the Drugs and Cosmetics Act, 1940 and the Rules thereunder.
1. The licence shall be in force from……………………..to………………… 2. Name (s) of qualified person (s) in charge…………………………………. 3. Categories of drugs……………………………
Date……………………… Licensing Authority……………..
* Delete whichever is applicable Conditions of Licence
1. This licence shall be displayed in a prominent place in a part of the premises open to the public.
2. The licence shall comply with the provisions of the Drugs and Cosmetics Act, 1940 and the Rules thereunder for the time being in force.
_____________________________________________________________________ 1 Subs. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985 2 Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982
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3. The licence shall report to the Licensing Authority any change in the qualified staff in-charge within one month of such change.
4. No drug shall be sold unless such drug is purchased under cash or credit memo from a duly licensed dealer or a duly licensed manufacturer.
5. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm taken place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution.
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FORM 20-A [See Rule 61 (1)]
Restricted 1[Licence to sell, stock or exhibit or offer for sale, or distribute] drugs by retail other than those specified in2[Schedules C, C (1) and X] for3[* **] dealers who do not engage
the services of a qualified person.
I ………………………..is hereby 1[licensed to sell, stock or exhibit or offer for sale or distribute] on the premises situated at 3[* * *]…………….the following drugs being drugs other than those specified in 2[Schedules C,C (1) and X] of the Drugs and Cosmetics Rules, 1945, subject to the conditions specified below and to the provisions of the Drugs and Cosmetics Act, 1940 and the Rules made thereunder.
1. The licence shall be in force from……………………to………………..
2. The licensee can deal only in such drugs as can be sold without the supervision of qualified person under the Drugs and Cosmetics Rules, 1945.
3. The licence, if he be an itinerant vendor, shall buy drugs only from the following dealers and such other dealers as may be endorsed on the licence by Licensing Authority from time to time.
4. [ * * * Omitted as per G.O.I. Notification No. GSR 504(E) dt 18.7.2002.]
____________________________________________________________________ 1Subs. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985 2Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982 3Omitted by G.O.I. Notification No. GSR 231(E) dt 4.6.1996
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Name of the dealer…………………………. Licence No………………….
Date………………. Licensing Authority
Conditions of Licence
1. This licence shall be displayed in a prominent place in a part of the premises open to the public. [* * * Omitted by G.O.I. Notification No. GSR 231(E) dt 4.6.1996].
2. The licensee shall comply with the provisions of the Drugs and Cosmetics Act, 1940 and the Rules thereunder for the time being in force.
3. No drug shall be sold unless such drug is purchased under a cash or credit memo from a duly licensed dealer or a duly licensed manufacturer.
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution.
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FORM 20-B [See Rule 61 (1)]
1[Licence to sell, stock or exhibit or offer for sale, or distribute] by wholesale, drugs other than specified in2[Schedules C, C(I) and X]
1. …………………………… hereby 1[licensed to sell, stock or exhibit or offer for sale or distribute] by wholesale drugs other than those specified in 2[Schedule C,C(1) and X] on the premises situated at……………………subject to the conditions specified below and to the provisions of the Drugs and Cosmetics Act, 1940, and the Rules thereunder.
2. The licence shall be in force from ……………….. to…………………..
3[3. The sale shall be made under the personal supervision of a competent person (Name of the competent person.)]
_______________________________________________________________________ 1Subs. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985 2Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982 3 Ins. by G.O.I. Notification No. GSR 681(E) dt 6.6.1988.
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Date…………………… Licence No………………… Licensing Authority
Conditions of Licence
1. This licence shall be d isplayed in a prominent place in part of the premises open to the public
2. The licensee shall comply with the provisions of the Drugs and Cosmetics Act, 1940 and the Rules thereunder for the time being in force.
13.(i) No drug shall be sold unless such drug is purchased under a cash or credit memo from a duly licensed dealer or a duly licensed manufacturer.
(ii) No sale of any drug shall be made to a person not holding the requisite licence to sell, stock or exhibit for sale or distribute the drug. Provided that this condition shall not apply to the sale of any drug to--
(a) an officer or authority purchasing on behalf of Government or (b) a hospital, medical, educational or research institution or a registered medical
practitioner for the purpose of supply to his patients, or (c) a manufacturer of beverages, confectional biscuits and other non-
medicinal products, where such drugs are required for processing these products;
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm taken place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the changes takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution.
____________________________________________________________________________ 1 Amended by G.O.I. Notification No. F.1/63/61-D, dtd 17.7.1963.
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1[FORM 20-BB [See Rule 62-D]
2[Licence to sell, stock or exhibit or offer for sale by wholesale, or distribute] drugs other than those specified in Schedule C and Schedule C (1) to the Drugs and Cosmetics Rules, 1945 from
a motor vehicle.
1.__________________________is hereby 2[licensed to sell, stock or exhibit or offer for sale by wholesale, or distribute] to sell by wholesale, or to distribute drugs other than those specified in Schedule C and Schedule C (1) from the vehicle bearing registration no._________________________ assigned under Motor Vehicle Act, 1939, subject to the conditions specified below and to the provisions of the Drugs and Cosmetics Act, 1940 and the Rules made thereunder.
2. The licence shall be in force from__________________ to______________ 3. Categories of drugs…………………………………
Date _______________________ Licence No.__________________
Licensing Authority
Conditions of Licence
1. This licence shall be displayed in prominent place on the vehicle. 2. The licence shall comply with the provisions of the Drugs and Cosmetics Act, 1940
and the Rules made thereunder for the time being in force. 3(i)No drugs shall be sold by wholesale or distributed unless such drug is purchased
under a cash or credit memo from a duly licensed dealer or a duly licensed manufacturer.
(ii) No sale by wholesale or distribution of any drug shall be made to a person not holding the requisite licence to sell, stock, or exhibit for sale or distribute the drug:
Provided that this condition shall not apply to the sale of any drug to—
a) an officer or authority purchasing on behalf of the Government, or
b) a hospital, medical, educational or research institution or a registered medical practitioner for the purpose of supply to his patients, or
c) a manufacturer of beverages, confectionary, biscuits and other non-medical products where such drugs are required for processing these products.
___________________________________________________________________ 1 Added by G.O.I. Notification No. X. 11013/7/76-D&MS, dtd 25.1.1979. 2 Subs. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985
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4. The licensee shall inform the Licensing Authority in writing in the event of change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution.
5. The licensee shall inform the Licensing Authority in writing in the event of any change in ownership of the vehicle specified in this licence within seven days of such change.
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1FORM 20-C
[See Rule 67-C]
2[Licence to sell, stock or exhibit or offer for sale or distribute] Homoeopathic medicines by retail
1. …………………………..is hereby licensed to sell, stock or exhibit for sale or distribute by retail Homoeopathic medicines on the premises situated at…………………….subject to the conditions specified below and to the provisions of the Drugs and Cosmetics Act, 1940 and the Rules made thereunder.
2. The licence shall be in force from…………………..to……………… 3. Name of the competent person-in-charge.
Date…………………….. Licensing Authority
Conditions of Licence
1. The licence shall be displayed in a prominent place in a part of the premises open to the public.
2. The licensee shall comply with the provisions applicable to homoeopathic medicines under the Drugs and Cosmetics Act, 1940 and the Rules made thereunder for the time being in force.
3. The licensee shall report to the Licensing Authority any change in the competent staff within one month of such change.
34. This licence authorises the sale of Homoeopathic medicines made from one earlier potency up to a quantity of 30ml at a time.
_____________________________________________________________________ 1Added under G.O.I. Notification No. F. 1-35/64-D dtd 18.8.1964. 2 Subs. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985 3 Added under G.O.I.Notification No. F. 1-59/68-D, dtd 19.11.1969.
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15. Where any change in the constitution of the firm takes place, a licensee shall inform the Licensing Authority in writing about the same and the current licence shall be valid only for a period of three months from the date on which the change takes place unless, in the meantime, name of the form with the changed constitution.
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2FORM 20-D
[See Rule 67-C]
3[Licence to sell, stock or exhibit or offer for sale or distribute] Homoeopathic medicines by wholesale.
1. …………………………….is hereby 3[licensed to sell, stock or exhibit or offer for sale or distribute] by wholesale Homoeopathic medicines on the premises situated at…………………………………….subject to the conditions specified below and to the provisions of the Drugs and Cosmetics Act. 1940 and the Rules made thereunder.
2. The licence shall be in force from…………………………..
Date…………………. Licensing Authority
Conditions of Licence
1. This licence shall be displayed in a prominent place on the premises.
2. The licence shall comply with the provisions as applicable to Homoeopathic medicines under the Drugs and Cosmetics Act, 1940 and the Rules made thereunder for the time being in force.
3. No sale of any drug shall be made to a person not holding the requisite licence to sell, stock or exhibit for sale or distribute the drug. Provided that this condition shall not apply to the sale of any drug to (a) an authority purchasing on behalf of Government, or (b) a hospital, medical, educational or research institute or a Homoeopathic medical practitioner for the purpose of supply to his patients.
14 The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence and the current licence shall be valid only for a period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution.
_____________________________________________________________________ 1Added under G.O.I. Notification No. G.S.R. 665, dtd 28-5-1977.. 2Added under G.O. Notification No. F.1-35/64-D, dtd 18.8.1964. 3Subs. by G.O.I. Notification No.GSR 788(E) dt 10.10.1985
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1FORM 20-E [See Rule 67-EE]
Certificate of renewal of 2[Licence to sell, stock or exhibit or offer for sale or distribute] Homoeopathic medicines.
1. Number of licence and date of issue……………………………….certified that licence no………………….in Form 20-C / 20D granted on the …………….to………….for sale of Homoeopathic medicines at the premises situated at…………..has been renewed for a period from……..to………………….
2. Name of competent persons in-charge.
Date………………… Licensing Authority
________________
3[FORM 20-F [See Rule 61(3)]
Licence to sell, stock or exhibit for sale or distribute by retail drugs specified in Schedule X 1. …….is hereby licensed to sell, stock or exhibit for sale or distribute by retail drugs specified in Schedule X to the Drugs and Cosmetics Rules, 1945 on the premises situated at ………………………………….
2. Name of drugs 3. This licence shall be in force from ……………. to ………………... 4. Name(s) of qualified person-in-charge. 5. the licence is subject to the conditions stated below and the provisions of the Drugs and
Cosmetics Act, 1940 and the Rules, made thereunder.
Date: ……………. Licence No. ………..
Licensing Authrotity.
Conditions of the licence.
1. This licence shall be displayed in a prominent place in a part of the premises open to the public.
_________________________________________________________________________ 1Ins. by G.O.I. Notification No. F.1-14/67-D dt 3.2.1969. 2 Subs, by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 3 Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982
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2. The licencee shall report to the licensing authority any change in the qualified staff incharge within one month of such change.
3. No drug shall be stocked or sold unless such drug has been purchased under cash/credit memo from a duly licensed dealer or a duly licensed manufacturer.
4. The licensee shall inform the licensing authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless in the meantime, a fresh licence has been taken from the licensing authority in the name of the firm with the changed constitution.
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FORM 20-G
[See Rule 61(3)] 1[Licence to sell, stock or exhibit or offer for sale, or distribute] by wholesale
drugs specified in Schedule X.
1. …….is hereby licensed to sell, stock or exhibit for sale or distribute by retail drugs specified in Schedule X to the Drugs and Cosmetics Rules, 1945 on the premises situated at ………………………………….
2. Name of drugs 3. This licence shall be in force from ……………. to ………………... 4. The licence is subject to the conditions stated below and the provisions of the Drugs
and Cosmetics Act, 1940 and the Rules, made thereunder.
Conditions of the licence.
1. This licence shall be displayed in a prominent place in a part of the premises open to the public.
2. The licensee shall comply with the provisions of the Drugs and Cosmetics Act, 1940 and the rules made thereunder.
3. No drug shall be stocked or sold unless such drug has been purchased under a cash or credit memo from a duly licensed dealer or a duly licensed manufacturer.
4. The licensee shall forward to the licensing authority copies of the invoices of sales made to the retail dealers.
5. No sale of any drug by wholesale shall be made to a person not possessing the requisite licence to sell, stock or exhibit for sale or distribute drugs specified in Schedule X :
____________________________________________________________________ 1Subs, by G.O.I. Notification No. GSR 788(E) dt 10.10.1985.
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Provided that this condition shall not apply to the sale of any drug to –
(a) an officer or authority purchasing on behalf of Government;
(b) a hospital, medical, educational or research institution, nursing home, Registered Medical Practitioner for the purpose of supply to its/his patients or manufacturer holding a licence in Form 25-E or 28-B to manufacture the drugs containing drug included in Schedule X.]
1[The licensee shall inform the licensing authority in writing in the event of any change in the constitution of the firm operating under the licence, where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless in the meantime, a fresh licence has been taken from the licensing authority in the name of the firm with the changed constitution.]
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FORM 21 [See Rule 61 (2)]
1[Licence to sell, stock or exhibit or offer for sale distribute] by retail drugs specified in Schedules C and C (1) 2[excluding those specified in Schedule X.]
31. …………………..is hereby 1[licensed to sell, stock or exhibit or offer for sale or distribute] by retail the following categories of drugs specified in Schedules C and C (1) 2[excluding those specified in Schedule X.] to the Drugs and Cosmetics Rules, 1945* and to operate a pharmacy on the premises situated at……………..subject to the conditions specified below and to the provisions of the Drugs and Cosmetics Act, 1940 and the Rules thereunder.
2. The licence shall be in force from………….to……………… 3. Name(s) of qualified persons in charge………………………….
34. Categories of drugs…………………………………………..
Date………………………… Licensing Authority Licence No…………………………
*Delete if not applicable.
________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 2 Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982 3 Amended by G.O.I. Notification No. S.O. 2139 dt 12-8-1972.
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Conditions of Licence
1. This licence shall be displayed in a prominent place in a part of the premises open to the public.
2. The licensee shall report to the Licensing Authority any change in the qualified staff in charge within one month of such change.
3. [ * * * Omitted by G.O.I.Notification No. GSR 17(E) dt 7.1.1986.]
4. If the licensee wants to sell, stock or exhibit for sale or distribute, during the currency of the licence, additional categories of drugs listed in Schedules C and C (1) 2[excluding those specified in Schedule X.]but not included in this licence, he should apply to the Licensing Authority for the necessary permission. This licence will be deemed to extend to the categories of drugs in respect of which such permission is given. This permission shall be endorsed on the licence by the Licensing Authority.
15 No drug shall be sold unless such drug is purchased under a cash or credit memo from a duly licensed dealer or a duly licensed manufacturer.
6. The licence shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place, unless in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution.
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FORM 21-A [See Rule 61 (2)]
3Licence to sell, stock or exhibit or offer for sale distribute] by retail drugs specified in 5[Schedules C (1)] 4[* * *] dealers who do not engage the services of a qualified person.
1. …………………………..is hereby [licensed to sell, stock or exhibit or offer for sale or distribute] by retail on the premises situated at /4[* * *] …………………the following rugs being drugs specified in 5[Schedule C (1)] to the Drugs and Cosmetics Rules, 1945, subject to the conditions specified below and to the provisions of the Drugs and Cosmetics Act, 1940 and the Rules thereunder.
____________________________________________________________________________ 1 Ins. by G.O.I. Notification No. F. 1-63/61-D dtd 17.7.1963. 2 Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982 3 Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 4Omitted by G.O.I. Notification No. GSR 231(E) dt 4.6.1996 5 Subs. by G.O.I. Notification No. GSR 487(E) dt 2.7.1984.
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2. The licence will be in force from……………..to………………….. 3. Particulars of 1[Schedule C (1)] drugs to be sold…………………….
4. [ * * * Omitted as per G.O.I. Notification No. GSR 504(E) dt 18.7.2002.]
Date…………………. Licensing Authority……
Conditions of Licence
1. This licence shall be displayed in a prominent and conspicuous place in a part of the premises open to public or shall be kept on the process of the vendor who shall produce it on demand by an Inspector or an officer authorised by the State Government in this behalf.
2. [ * * * Omitted as per G.O.I. Notification No. GSR 17(E) dt 7.1.1986.]
3. The licensee shall deal only in such drugs as can be sold without the supervision of a “qualified person” as defined in the Explanation to sub -rule (15) of rule 65 of the Drugs and Cosmetics Rules, 1945.
4. No drug shall be sold unless such drug is purchased under cash or credit memo from duly licensed manufacturer.
5. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution.
FORM 21-B [See Rule 61 (2)]
2[Licence to sell, stock or exhibitor offer for sale or distribute] by wholesale drugs specified in Schedules C and C (1) 3[excluding those specified in Schedule X].
1…………………….is hereby licensed to sell, stock or exhibit for sale or distribute by wholesale on the premises situated at……………..the following categories of drugs specified in Schedule C and C (1) 3[excluding those specified in Schedule X] to the Drugs and Cosmetics Rules, 1945.
__________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 487(E) dt 2.7.1984. 2Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 3Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982
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Categories of drugs
2. This licence shall be in force from……………to…………………
1[2-A. The sale shall be made under the person supervision of a competent person. (Name of the competent person.)].
3. This lic ence is subject to the conditions stated below and to the provisions of the Drugs and Cosmetics Act, 1940 and the Rules thereunder.
Licence No……………
Date…………………. Licensing Authority……
Conditions of Licence
1. This licence shall be displayed in a prominent place in a part of the premises open to the public.
2. [ * * * Deleted by G.O.I. Notification No. GSR 17(E) dt 7.1.1986.] 3. If the licensee wants to sell, stock or exhibit for sale or distribute during the
currency of the licence additional categories of drugs listed in Schedule C and C (1) 2[excluding those specified in Schedule X] but not included in this licence. He should apply to the Licensing Authority for the necessary permission. This licence will be deemed to extend to the categories of drugs in respect of which such permission is given. This permission shall be endorsed on the licence by the Licensing Authority.
34. (i) No drug shall be sold unless such drug is purchased under a cash or credit memo from a duly licensed dealer or a duly licensed manufacturer.
(ii) No sale of any drug shall be made for purposes of resale to a person not holding the requisite licence to sell, stock or exhibit for sale or distribute the drug.
Provided that this condition shall not apply to the sale of any drug to —
(a) an officer or authority purchasing on behalf of Government, or (b) a hospital, medical, educational or research institute or a registered medical
practitioner for the purpose of supply to his patients, or 4(c) a manufacturer of hydrogenated vegetable oils, beverages, confectionary and other
non-medicinal products, where such drugs are required for processing these products
____________________________________________________________________________ 1Ins. by G.O.I. Notification No.GSR 681(E) dt 6.6.1988. 2Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982 3Added under G.O.I. Notification No. F. 1-63/61-D, dtd 17.7.1963. 4Added under G.O.I. Notification No. F. 1-113/69-D, dtd 23.12.1969.
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5. The licence shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from Licensing Authority in the name of the firm with the changed constitution.
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FORM 21-BB [See Rule 62-D]
Licence to sell by wholesale or to distribute drugs specified in Schedule C and Schedules C (1) to the Drugs and Cosmetics Rules, 1945 from a motor vehicle.
1 ……………………is hereby licensed to sell by wholesale, or to distribute drugs specified in Schedule C and Schedule C (1) from the vehicle bearing registration no. ………………………..assigned under Motor Vehicles Act, 1939, subject to the conditions specified below and to the provisions of the Drugs and Cosmetics Act, 1940 and the Rules made thereunder.
2. The licence shall be in force from …………….. to……………..
3. Categories of drugs………………………………………..
Date …………… Licence No. ……………………..
Licensing Authority
Conditions of licence
1. This licence shall be displayed in a prominent place on the vehicle.
2. No drugs to which this licence applies shall be sold by the Licensing Authority from time to time in the Official Gazette have been observed throughout the period during which it has been in the possession of the licensee.
3. If the licensee wants to sell by wholesale or distribute during the currency of the licence, additional categories of drugs listed in Schedule C and C (1) not included in this licence, he shall apply to the Licensing Authority for necessary permission. This licence shall be deemed to extend to the categories of drugs in respect of which such permission is given. This shall be endorsed on the licence by the Licensing Authority.
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4. (i) No drugs shall be sold by wholesale or distributed unless such drug is purchased under a cash or credit memo from a duly licensed manufacturer.
(ii) No sale for wholesale or distribution of any drug shall be made for the purpose of resale to a person, not holding the requisite licence to sell, stock or exhibit for sale or distribute the drug:
Provided that this condition shall not apply to the sale of any drug to.—
(a) an officer or authority purchasing on behalf of the Government.
(b) a hospital, medical, educational or research institution or a registered medical practitioner for the purpose of supply to his patients, or
(c) a manufactures of hydrogenated vegetable oils, beverages, confectionary and other non-medical products, where such drugs are required for processing their products.
5. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution.
6. The licensee shall inform the Licensing Authority in writing in the event of any change in the ownership of the vehicle specified in this licence within seven days of such change.
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FORM 21 - C [See Rule 63-A]
Certificate of renewal of 1[licence to sell, stock or exhibit or offer for sale or distribute] drugs
1. Certified that licence No……………….in 2[Form 20, 20A, 20-B, 20-F, 20-G, 21, 21-A, 21-B], granted on the…………….to………….for sale of the following drugs at the premises situated at……………has been renewed for a period from…………………to……….
2. Categories or particulars of drugs……………………………….
3. Name (s) of qualified person (s) in-charge……………………..
Date………………………. Licensing Authority _________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 2Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982
242
FORM 21-CC [See Rule 63-B]
Certificate of renewal of 1[licence to sell, to stock or exhibit or offer for sale by wholesale or distribute] drugs from a motor vehicle.
Number of licence and date of issue_________________________________
1. Certified that licence no. _________ in Form 20-BB or Form 21-BB granted on the __________________________ to ________________________ for sale by wholesale or distribution of the following drugs from the vehicle having registration No. ____________________________ assigned under the Motor Vehicle Act, 1939 has been renewed for a period from _________________ to ____________________________
2. Categories of the drugs: ______________________ ________________________ ______________________ ________________________
Date ___________________ Licensing Authority
FORM 24 [See Rule 69]
Application for the grant of or renewal of a 1[ licence to manufacture for sale or for distribution of] drugs other than those specified in Schedules C and C (1).
1. I / We …………………………..of………………………… hereby apply for the grant / renewal of a licence to manufacture on the premises situated at ……………….. the following drugs being drugs other than those specified in Schedules C and C (1) of the Drugs and Cosmetics Rules, 1945.
2. Names of drugs categorized according to Schedule M. ……………………………… .
3. Names, qualifications and experience of technical staff employed for manufacture and testing.
4. A fee of rupees ………………………………. has been credited to Government under the head of account……………………………………………..
Date……………………… Signature…………….
NOTE.—The application should be accompanied by a plan of the premises. ___________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985
243
FORM 24-A [See Rule 69-A]
Application for grant or renewal of a loan 1[licence to manufacture for sale or for distribution of] drugs other than those specified in Schedule C and C (1).
1. I / We*…………………………………off …………………………..hereby apply for the grant / renewal of a loan licence to manufac ture on the premises situated at…………………………………………..C /o§ ………………………… the under- mentioned drugs, other than those specifies in Schedule C and C (1) to the Drugs and Cosmetics Rules.
Names of drugs (each substance to be separately specified).
2. The names, qualifications and experience of the expert staff actually connected with the manufacture and testing of the specified products in manufacturing premises.
4. I / We enclose
(a) A true copy of a letter from me / us to the manufacturing concern whose manufacturing capacity is intended to be utilized by me / us.
(b) A true copy of a letter from the manufacturing concern that they agree to lend the services of their expert staff, equipment and premises for manufacture of each item required by me / us and that they will analyze every batch of finished product and maintain the registers of raw materials, finished products and reports of analysis separatly in this behalf.
(c) Specimens of labels, cartons of the products proposed to be manufactured.
4, A fee of rupees ……………………………………….has been credited to Government under the head of account ……………………………………
Date …………………………. Signature…………………….
* Enter here the name of the proprietor, partners of Managing Director as the case may be. f .Enter here the name of the applicant form and the address of the principal place of business. § Enter here the name and address of the manufacturing concern where the manufacture will be actually carried out and also the Licence number under which the latter operates.
___________________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985
244
FORM 24-B [See Rule 69]
Application for grant or renewal of licence to repack for sale or distribution of drugs, being drugs other than those specified in Schedules C and C (1) 1[excluding those specified in
Schedule X]
1. I / We ………………………..of ……………………………..hereby apply for grant / renewal of a licence to repack the following drugs at the premises situated at………………………………………………
2. Names of the drugs to be repacked……………………………………..
3. Name, qualification and experience of competent staff……………………
4. A fee of rupees forty has been credited to Government under the head of account……………………………………..
Date………………………….. Signature of applicant…………
NOTE :—The applications shall be accompanied by a plan of the premises. ___________________
1FORM 24-C [See Rule 85-B]
Application for the grant or renewal of a2[licence to manufacture for sale or for distribution of]Homoeopathic medicines or a licence to manufacture potentised preparations from back
potencies by licensees holding licence in Form 20-C
3[1. I / We ………………………….. of ……………………….. holder of licence no……………………………………in Form 20-C hereby apply for the grant / renewal of licence to manufacture the under mentioned Homoeopathic mother tinctures / potentised preparations on the premises situated at…………………….
Name of the Homoeopathic preparations………………………. (Each item to be separately specified)].
2. Names, qualifications and experience of technical staff employed for manufacture and testing of Homoeopathic medicines.
___________________________________________________________________________ 1Amended by G.O.I. Notification No. F. 1-598-D, dtd 19.11.1969 2Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985 3Subs. by G.O.I. Notification No. GSR 13(E) dt 7.1.1983.
245
3. A fee of rupees……………………….has been credited to Government under head of account…………………………………………………………………………
Date………………………. Signature…………………..
NOTE 1. Delete whichever portion is not applicable. 2. The application should be accompanied by a plan of the premises.
_________________
1FORM 24-D [See Rule 153]
Application for the grant / renewal of a licence to manufacture for sale of Ayurvedic / Siddha or Unani drugs
1. I / We ……………………….. of ………………………………..hereby apply for the grant / renewal of a licence to manufacture Ayurvedic (including Siddha) or Unani drugs on the premises situated at…………………………………….
2. Names of drugs to be manufactured (with details)
3. Names, qualification and experience of technical staff employed for manufacture and testing of Ayurvedic (including Siddha) or Unani drugs ………………………………..
4. A fee of rupees………………..has been credited to the Government under the head of account……………………….and the relevant Treasury Challan is enclosed herewith.
Date…………………………… Signature……………………….. (applicant)
NOTE—The application should be accompanied by a Plan of the premises. ____________________
2FORM 24-E
[See Rule 154-A]
Application for grant or renewal of a loan licence to manufacture or sale Ayurvedic (including Siddha) or Unani Drugs
1. I / We*……………………………………………..of**……………………hereby apply for the grant / renewal of a loan licence to manufacture Ayurvedic (including Siddha) or Unani Drugs…………………………………..on the premises situated at…………………………………………………………………………………….. C/o ***……………………………………………….. ____________________________________________________________________________ 1Ins. by G.O.I. Notification No.1-23/67-D dt 2.2.1970. 2 Added by G.O.I. Notification No.GSR 376 (E) dtd 20.7.1978.
246
2. Names of drugs to be manufactured (with details).
3. The names, qualifications and experience of technical staff actually connected with the manufacture and testing of Ayurvedic (including Siddha) or Unani drugs in the manufacturing premises.
4. I / We enclose,
a) A true copy of a letter from me / us to the manufacture concern whose manufacturing capacity is intended to be utilized by me / us.
b) A true copy of a letter from the manufacturing concern that they agree to lend the services of their competent technical staff, equipment and premises for the manufacture of each item required by me / us and that they shall maintain the registers of raw materials and finished products separatly in this behalf.
c) Specimen of labels, cartons of the drugs proposed to be manufactured.
4. A fee of Rs…………………………………..has been credited to Government under the head of account……………………….and the relevant Treasury Challan is enclosed herewith.
Date………………… Signature………………] (applicant)
____________________________________________________________________ * Enter here the name of the proprietor, partners or Managing Director as the case may be. ** . Enter here the name of the applicant firm and the address of the principal place of business. *** Enter here the name and address of the manufacturing concern where the manufacture will be actually carried out and also the licence number under which the letter operates.
________________
1[FORM 24-F
[See Rule 69]
Application for grant or renewal of a 2[licence to manufacture for sale or for distribution of] drugs specified in Schedule X and not specified in Schedules C and C(1).
1. I/We……………………. of …………………….. hereby apply for the grant/renewal of licence to manufacture on premises situated at …………………the undermentioned drugs, specified in Schedule X to the Drugs and Cosmetics Rules, 1945.
_________________________________________________________________________ 1 Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982 2Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985.
247
2. Name of drugs.
3. Names, qualifications and experience of technical staff employed for manufacture and testing.
4. A fee of rupees………….. has been credited to Government account under the head of account…………………………………
Signature…………… Date: …….. Designation ………..]
____________
FORM -25 [See Rule 70]
1[Licence to manufacture for sale or for distribution of] drugs other than those specified in Schedules C and C(1).
Number of Licence and date of issue…………………………………………
1…………………………………………….is hereby to manufacture the following categories of drugs being drugs other than those specified in Schedules C and C (1) to the Drugs and Cosmetics Rules, 1945, on the premises situated at………………………………………………………………under the direction and supervision of the following 2[competent technical staff]
a) 2[competent technical staff] b) Names of Drug (each item to be separately specified)…………………………
2. The licence authorizes the sale by way of wholesale dealing and storage for sale by the licensee of the drugs manufactured under the licence, subject to the conditions applicable to licence for sale.
3. The licence shall be in force from…………………………..to……………
__________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985 2 Subs. by G.O.I. Notification No. GSR 5(E) dt 6.1.1997.
248
4. The licence is subject to the conditions stated below and to such other conditions as may be specified in the Rules for the time being in force under the Drugs & Cosmetics Act, 1940.
Date………………………… Signature………………………
Designation……………………. 1[*Licensing Authority *Central Licence Appoving Authority.]
*Delete whichever is not applicable.
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to the Licensing Authority.
3. If the licensee wants to manufacture for sale additional items of drugs not included above he should apply to the Licensing Authority for the necessary endorsement as provided in Rule 69 (5). This licence will be deemed to extend to the categories so endorsed.
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with th e changed constitution.
_________________
FORM 25-A [See Rule 70-A]
Loan 2[licence to manufacture for sale or for distribution of] drugs other than those specified in Schedules C and C (1)
1. Number of licence and date of issue……………………………………… 2. ……………………………….of……………………..is hereby granted a loan
licence to manufacture the following drugs other than those specified in Schedules C and C (1) to the
______________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 923(E) dt 14.12.1992. 2 Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985
249
Drugs and Cosmetics Rules, 1945, on the premises situated at………………………………C/o……………………………………under the direction and supervision of the following 1[competent technical staff]
a) 1[competent technical staff] b) Name of drugs……………………………
3. The licence authorizes the sale by way of wholesale dealing and storage for sale by the licensee of the drugs manufactured under the licence subject to the conditions applicable to licences for sale.
4. The licence is subject to the conditions stated below and to such other conditions as may be specified in the Rules for the time being in force under the Drugs & Cosmetics Act, 1940.
Date…………………… Signature…………………… Designation…………………...
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to the Licensing Authority.
3. If the licensee wants to undertake during the currency of the licence the manufacture for sale additional drugs he should apply to the Licensing Authority for the necessary endorsement to the licence as provided in Rule 69-A. This licence will be deemed to extend to the drugs so endorsed.
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
______________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 923(E) dt 14.12.1992.
250
1FORM 25-B [See Rule 70]
Licence to repack for sale or distribution of drugs being drugs other than those specified in Schedules C and C (1) 2[excluding those specified in Schedule X]
Number of licence and date of issue……………………………………….
1……………………………of……………………….is hereby granted a licence to repack the following drugs for sale or distribution on the premises situated at…………………….under the supervision of the following competent staff.
a) Names of drugs to be repacked. b) Names of competent staff.
2. The licence shall be in force from……………………..to …………………
3. The licence authorizes the sale by way of wholesale dealing by the licensee and storage for sale by the licensee of the drugs repacked under the licence subject to conditions applicable to licences for sale.
4. The licence is subject to the conditions stated below and to such other conditions as may be specified in the Rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date……………………….. Signature……………………..
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to the Licensing Authority.
3. If the licensee wants to repack for sale or distribution additional items he should apply to the Licensing Authority for the necessary endorsement to this licence. This licence will be deemed to extend to only those items so endorsed.
____________________________________________________________________________ 1 Added under G.O.I.Notification No. F. 1-22/59-D, dtd 9-4-1960. 2 Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982
251
4. The drugs repacked under this licence shall bear on their label, apart from other particulars required by these Rules, the name and address of the licensee and the number of the licence under which the drug is repacked proceeded by the words “Rpg. Lic. No.”.
5. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
________________
1FORM 25-C [See Rule 85-D]
2[Licence to manufacture for sale or for distribution of] Homoeopathic medicines
Number of Licence and date of issue…………………………………….
3[1,…………………………………who holds a licence in Form 20-C is hereby licensed to manufacture Homoeopathic mother tinctures / potentised and other preparations on the premises situated at…………………………….under the direction and supervision of the following technical staff :
Name of the Homoeopathic preparations (Each item to be separately specified). Names of the Technical Staff …………………………]
2. The licence shall be in force from…………………………….to……………
3. The licence is subject to the conditions stated below and to such other conditions as may be specified in the Rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date……………………….. Signature………………………
Designation…………………….
_______________________________________________________________________ 1 Added under G.O.I. Notification No. F.1-36/64-D, dated 18th August 1964. 2 Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985 3 Subs. by G.O.I. Notification No. GSR 13(E) dt 7.1.1983.
252
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to the Licensing Authority.
13. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
______________
2FORM 25-D [See Rule 154]
Licence to manufacture for sale of Ayurvedic (including Siddha) or Unani drugs
No. of Licence…………………………..
1……………………………is / are hereby licensed to manufacture the following Ayurvedic (including Siddha) or Unani drugs on the premises situated at……………………………………………………………….under the direction and supervision of the following technical staff: —
a) Technical staff (Name) b) Names of drugs (each item to be separatly specified).
2. The licence shall be in force from…………………………..to……………
_____________________________________________________________________ 1 Added by G.O.I. Notification No.S.O. 903 dtd 28-2-1976. 2 Added under G.O.I. Notification No. 1-23/67-D, dtd 2-2-1970
253
3. The licence is subject to the conditions stated below and to such other conditions as may be specified in the Rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date……………………………… Signature………………
Designation……………
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to the Licensing Authority.
3. This licence shall be deemed to extend to such additional items as the licensee may intimate to the Licensing Authority from time to time, and as may be endorsed by the Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
______________
1FORM 25-E [See Rule 154-A]
Loan Licence to manufacture for sale Ayurvedic (including Siddha) or Unani Drugs
1. Number of Licence………………………………….
2…………………………………..of……………………………is hereby granted a loan licence to manufacture for sale Ayurvedic (including Siddha) or Unani drugs, on the premises situated at…………………………………C/o…………………………………under the direction and supervision of the following expert technical staff.
a) Technical staff b) Names of drugs (each item to be separately specified)
_________________________________________________________________________ 1 Added by G.O.I. Notification No. GSR 376 (E), dtd 20.7.1978
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3. The licence shall be in force from………………….to………………………
4. The licence is subject to the conditions stated below and to such other conditions as may be specified in the Rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date of Issue………………………………. Signature………………….
Designation………………..
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to the Licensing Authority.
3. This licence shall be deemed to extend to such additional items as the licensee may intimate to the Licensing Authority from time to time, and as may be endorsed by the Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
______________
1[FORM 25-F
[See Rule 70]
2[Licence to manufacture for sale or for distribution of] drugs specified in Schedule X and not specified in Schedules C and C(I).
1. ………………………….. of ……………. is hereby licensed to manufacture at the premises situated at …………… the following drugs specified in Schedule X to the Drugs and Cosmetics Rules, 1945.
2. Name of drugs.
3. Names of approved 1[competent technical staff]
____________________________________________________________________________ 1Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982 2Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985.
255
4. The licence authorizes the sale by way of wholesale dealing and storage for sale by the licensee of the drugs manufactured under the licence subject to the onditions applicable to licence for sale.
5. The licence shall be in force ……….. to ……………………..
6. The licence is subject to conditions stated below and to other conditions as may be specified in the rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date of issue …………. Signature ………………….. Licence No. …………… Designation………………..
2[*Licensing Authority *Central Licence Approving Authority.
Conditions of Licence
1. The licence and any certificate of renewal in force shall be kept on the licensed premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. If the licensee wishes to undertake during the currency of the licence the manufacture of any drug specified in Schedule X not included above, he should apply to the Licensing Authority for the necessary endorsement of this licence. This licence shall be deemed to extend to only those items so endorsed.
3. Any change in the 1[competent technical staff] shall be forthwith reported to the Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
5. The licensee shall furnish to the Licensing Authority copies of the invoices of sales made to dealers.
6. The licensee shall not manufacture drugs covered by this licence for use as ‘Physician’s Samples’.]
_________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 231(E) dt 4.6.1996. 2Subs. by G.O.I. Notification No. GSR 923(E) dt 14.2.1992.
256
1[FORM 26 [See Rules 73 and 83]
Certificate of renewal of licence to manufacture for sale of drugs other than those specified in Schedule X
1. Certified that licence no……………………………………………granted on the…………..to………………for the manufacture of the following categories of drugs being *drugs other than those specified in Schedules C and C (1) and X *drugs covered by Schedules C and C (1) excluding those specified in Schedule X to the Drugs and Cosmetics Rules, 1945, at the premises situated at ……………. ……………………….has been renewed from………………to ……………
2. Name (s) of 2[competent technical staff]……………….. 3[3 Name of the drugs (each item to be separately specified) …………..]
Signature………………….. Date ……… Designation……………
*Delete whatever portion is not required.
___________________
1FORM 26-A [See Rules 73-A and 83-A]
Certificate of renewal of loan licence to manufacture for sale of drugs other than those specified in Schedule X
1. Certified that loan licence No………………………………………..granted on the……………………………..to…………………………...for the manufacture of the under mentioned drugs being *drugs other than those than drugs in Schedule C, C (1) and X drugs specified in Schedules C and C (1) excluding those specified in Schedule X. to the Drugs and Cosmetics Rules, 1945, at the premises situated at…………………..C/o……………….has been renewed from………………..to……………
2. Names of the drugs (each substance to be separately specified).
___________________________________________________________________________ 1 Subs.by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 2 Subs. by G.O.I. Notification No. GSR 231(E) dt 4.6.1996 3 Ins. by G.O.I. Notification No. GSR 370(E) dt 7.4.1994.
257
3. Name of the 1[competent technical staff] Signature……………….
Designation…………….. Date…………………….
* Delete whichever is not applicable. ______________
2FORM 26-B [See Rule 73-B]
Certificate of renewal of licence to repack for sale or distribution of drugs being drugs other than those specified in Schedules C and C (1) 3[excluding those specified in
Schedule X]
1. Certified that licence No…………………………granted on the………………to……………………….for the repacking of the following drugs at the premises situated at………………………….has been renewed from……………. to…………………………………………
Names of drugs to be repacked……………………………….
2. Names of competent staff…………………………
Date : …… Signature ……………. Designation ……………… 4[*Licensing Authority. * Central Licence Approving Authority.
* Delete whichever is not applicable.
_________________
FORM 26-C [See Rule 85-G]
Certificate of renewal of licence to manufacture for sale of Homoeopathic medicines
1. Certified that licence No………………..granted on the ………….to……………for the manufacture for sale of the Homoeopathic mother tinctures / potentised preparation at the premises situated at……………………..has been renewed for a period from the…………………..to……………………….
_________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 231(E) dt 4.6.1996 2Added under G.O.I. Notification No. F.1-22/59-D, dtd 9.4.1964 3Subs.by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 4Subs. by G.O.I. Notification No. GSR 923(E) dt 14.2.1992.
258
2. Name of the technical staff…………………………………….. 1[3. Names of the drugs (each item to be separately specified) …………]
Signature…………………….. Designation……………………...
Date……………………………….
________________
2FORM 26-D [See Rule 155]
Certificate of renewal of licence to manufacture for sale of Ayurvedic / Siddha or Unani drugs
1. Certified that licence No…………………………….granted on the…………………………………………to Shri/ Messers…………………………..for the manufacture of Ayurvedic/Siddha/Unani drugs at the premises situated at………………..has been renewed from………………………….to………………………….
2. Name of technical staff………………………………………….
33. Names of drugs (each item to be separately specified).]
Signature………………. Designation…………….
Date……………………… ----------------------
3FORM 26-E [See Rule 155-A]
Certificate of renewal of loan licence to manufacture for sale of Ayurvedic / Siddha or Unani Drugs
1. Certified that Loan Licence No…………………..granted on the………………………………………to…………………………….for the manufacture of Ayurvedic / Siddha or Unani drugs at the premises situated at……………………………………………….C/o………………………..has been renewed from……………………………………….to………………………………….
__________________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 370(E) dt 7.4.1994. 2Ins. by G.O.I. Notification No. 1-23/67-D, dtd 2-2-1970. 3Ins. by G.O.I. Notification No. GSR 376 (E), dtd 20.7.1978
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2. Name of technical staff……………………………………………….
Date…………………………. Signature………………….. Designation………………..
_______________
1[FORM 26-E-1
(See Rule 157 155-B)
(Certificate of Good Manufacturing Practices (GMP) to manufacture of Ayurveda, Siddha or Unani drugs):
Certified that manufacturing unit licensee, namely …………...situated at ………… State ………….. Licence No. ……………… comply with the requirements of Good Manufacturing Practices of Ayurveda-Siddha-Unani drugs as laid down in Schedule T of the Drugs and Cosmetic Rules, 1945.
This certificate is valid for a period of three years.
Dated :….. Signature …………. Place : …. Designation ………..
Licensing Authority for Ayurveda/ Siddha/ Unani Drugs.]
______________
2[FORM 26-F
[See Rules 73 and 83]
Certificate of renewal of licence to manufacture for sale of drugs specified in Schedule X
1. Certified that licence No. ……………….. granted on the ……….. to ………. For the manufacture of drugs specified in Schedule X to the Drugs and Cosmetics Rules, 1945, at the premises situated at ………………… has been renewed from ………… to ………….
2. Names of drugs (each substance to be separately specif ied). _________________________________________________________________________ 1Ins. by G.O.I. Notification No.GSR561(E) dt 23.6.2000 and subs. By G.O.I.Notification No.G.S.R.198(E) dt.07.03.2003. 2 Ins. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982.
260
3. Names of the 1[competent technical staff].
Signature ……………. Designation ……………… 2[*Licensing Authority. * Central Licence Approving Authority.
* Delete whichever is not applicable.
Date of issue ……………………….. ____________________
3[FORM 26-G
[See Rule 122-F]
Certificate of renewal of licence to operate f Blood Bank for processing of whole human blood and/or* for preparation for sale or distribution of its components.
1. Certified that Licence No………….. granted on ……………… to M/s. ……………… for the operation of a Blood Bank for processing of whole human blood and/or for preparation of its components at the premises situated…………………….. is hereby renewed with effect from …………….. to ……………..
2. Name(s) of items : 1. 2. 3.
3. Name(s) of competent Technical Staff: 1. 2. 3. 4. 5.
Date ……….. Signature ……………… Name and Designation ………
Licensing Authority. Central Licence Approving Authority.
* Delete whichever is not applicable.]
________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 231(E) dt 4.6.1996. 2Subs. by G.O.I. Notification No. GSR 923(E) dt 14.12.1992. 3Subs. by G.O.I. Notification No. GSR 244(E) dt 5.4.1999.
261
1[FORM 26-H
[See Rules 68-A, 76, 78]
Certificate of renewal of licence to manufacture for sale of Large Volume Parenterals/Sera and Vaccines specified in Schedules C and C(I)
excluding those specified in Schedule X.
1. Certified that Licence No. …………. granted on the ………… to……… for the manufacture of following Large Volume Parenterals/Sera and Vaccines at the premises situated at …………….has been renewed from …………… to …………….
2. Name(s) of drug(s) ………………………(each item to be separately specified).
3. Name(s) of competent technical staff:
(a) responsible for manufacturing (b) responsible for testing
a) 1. b) 2. c) 3. d) 4.
Signature ……………… Designation …………………. Licensing Authority Central Licence Approving Authority
Date ……………………..]
___________________
2[FORM 26-I [See Rules 122-I]
Certificate of renewal of licence for manufacture of blood products.
1. Certified that Licence No. …………. granted on the ………… to……… for the manufacture of blood products at the premises situated at …………….has been renewed from …………… to …………….
2. Name(s) of item (s). 1. 2. 3.
_________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 119(E) dt 11.3.1996. 2Ins. by G.O.I. Notification No. GSR 245(E) dt 5.4.1999.
262
3.Name(s) of competent technical staff:
(a) responsible for manufacturing (b) responsible for testing
1. 1. 2. 2. 3. 3. 4. 4.
Signature ……………… Designation …………………. Licensing Authority Central Licence Approving Authority
Date ……………………..]
___________________
FORM -27 Application for grant or renewal of a 1[licence to manufacture for sale or for
distribution of] drugs specified in Schedules C and C (1) 2[excluding those specified in Schedule X]
1. I / We ……………………………………hereby apply for the grant / renewal of a licence to manufacture on the premises situated at…………………………..the under mentioned drugs, being drugs specified in Schedule C and C (1) 2[excluding those specified in Schedule X] to the Drugs and Cosmetics Rules, 1945.
Names of drugs (each item to be separately specified).
2. The names, qualifications and experience of the expert staff responsible for the manufacture and testing of the above mentioned drugs.
a) Name (s) of staff responsible for test……………………… b) Name (s) of staff responsible for manufacture……………….
3. The premises and plan are ready for inspection will be ready for inspection on
4. A fee of rupees ……………………. ……………and an inspection fee of rupees
___________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 2Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982.
263
has been credited to Government under the head of account.
Date…………………………. Signature………………… Designation……………………
FORM 27-A [See Rule 75-A]
Application for grant or renewal of a loan 1[licence to manufacture for sale or for distribution of] drugs specified in Schedules C and C (1)
1. I / We*……………………….of**………………………………..hereby apply for the grant / renewal of Loan Licence to manufacture on the premises situated at……………………………………………C/o***…………………………………… the undermentioned drugs, being drugs specified in Schedules C and C (1) to the Drugs and Cosmetics Rules.
Names of drugs (each substance to be separately specified) .
2. The names, qualifications and experience of the expert staff actually connected with the manufacture and testing of the specified products in the manufacturing premises.
a) Name (s) of expert staff responsible for manufacture………………. b) Name (s) of the expert staff responsible for testing…………………….
3. I /We enclose
(a) A true copy of a letter from me / us to manufacturing concern whose manufacturing capacity is intended to be utilized by me / us.
(b) A true copy of a letter from the manufacturing concern that they agree to lend the services of their competent technical staff, equipment and premises for the manufacture of each item required by me / us and that they shall maintain the registers of raw materials, finished products and reports of analysis separately on this behalf.
(c) Specimens of labels, cartons of the drugs proposed to be manufactured.
* Enter here name of the proprietor, partners or Managing Director, as the case may be. ** Enter here name of the applicant firm and the address of the principal place of business. *** Enter here the name and address of the manufacturing concern where the manufacture will
be actually carried out and also the licence number under which the latter operates.
_________________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985.
264
4. A fee of Rs…………………………………..has been credited to Government under the head of account………………………………………………..
Date………………………… Signature……………….. Designation……………………..
___________________
1[FORM 27-B
Application for grant or renewal of a 2[licence to manufacture for sale or for distribution of] drugs specified in Schedule C, C(I) and X
1. I/We ………………. of ………………..hereby apply for the grant/renewal of a licence to manufacture on the premises situated at …………………….the under-mentioned drugs, specified in Schedule C, C(I) and X to the Drugs and Cosmetics Rules, 1945.
2. Name of drugs.
3. The names, qualifications and experience of the expert staff responsible for the manufacture and testing of the above-mentioned drugs:
(a) Name(s) of staff responsible for testing (b) Name(s) of staff responsible for manufacture.
4. The premises and plant* are ready for inspection/will be ready for inspection on ……...
5. A fee of rupees ……………………………….and an inspection fee of rupees…….has been credited to the Government under the head of account………………….
Date ………….. Signature …………..
The application shall be accompanied by a plan of the premises.] * Delete whichever is not applicable.
________________
3[FORM 27-C [See Rule 122-F]
Application for grant/renewal* of licence for the operation of a Blood Bank for processing of whole blood and/or* preparation of Blood Components.
1. I/We…………………….of M/s………………………………….hereby apply for the grant of licence/renewal of licence number………..dated………..to operate a Blood Bank, for processing of whole blood and/or* for preparation of its components on the premises situated at……………………..
2. Name(s) of the item(s)
265
1. 2.
__________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 2 Ins. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 3 Subs. by G.O.I. Notification No.GSR 245(E) dt 5.4.1999.
3.
3. The name(s), qualification and experience of competent Technical Staff are as under:
(a) Name(s) of Medical Officer, (b) Name(s) of Technical Supervisor (c) Name(s) of Registered Nurse. (d) Name(s) of Blood Bank Technician.
4. The premises and plant are ready for inspection/will be ready for inspection on……..
5. A licence fee of rupees ……………….and an inspection fee of rupees…………..has been credited to the Government under the Head of Account………………(receipt enclosed).
Signature……………….. Dated………… Name and Designation………….
* Delete whichever is not applicable.
Note :
1. The application shall be accompanied by a plan of the premises, list of machinery and equipment for collection, processing, storage and testing of whole blood and its components, memorandum of association/constitution of the firm, copies of certificate relating to educational qualifications and experience of the competent technical staff and documents relating to ownership or tenancy of the premises.
2. A copy of the application together with the relevant enclosures shall also be sent to the Central Licence Approving Authority and to the Zonal/Sub-Zonal Officers concerned of the Central Drugs Standard Control Organization].
______________
1[FORM 27-D [See Rule 75]
Application for grant or renewal of a licence to manufacture for sale or for distribution of Large Volume Parenterals/Sera and Vaccines excluding those
specified in Schedule X. _________________________________________________________________________
1 Ins. by G.O.I. Notification No. GSR119(E) dt 11.3.1996.
266
1. I/We………………………of……………………..hereby apply for grant/renewal of a licence to manufacture for sale or distribution on the premises situated at………………….the under-mentioned Large Volume Parenteral/Sera and Vaccines, specified in Schedules C and C(1) to the Drugs and Cosmetics Rules, 1945.
2. Name(s) of drug(s)……………………………(each item to be separately specified).
3. The name(s), qualification and experience of the competent technical staff responsible for the manufacture of the above mentioned drugs.
(a) Name(s) of staff responsible for testing…………………… (c) Name(s) of staff responsible for manufacturing………………..
4. The premises and plant are ready for inspection/will be ready for inspection on………
5. A fee of rupees……………………...and an inspection fee of rupees……….has been credited to the Government under the Head of Account……………….
Date: ……….. Signature…………………….. Designation…………………
* Delete whichever is not applicable. Note :
1. The application is to be accompanied by a plan of the premises, list of machinery and equipment to be employed for manufacture and testing, memorandum of association/constitution of the firm, copies of certificate relating to educational qualifications and experience of the competent technical staff and documents relating to ownership or tenancy of the premises.
2. A copy of the application together with the relevant enclosures shall also be sent each to the Central Licence Approving Authority and concerned Zonal/Sub-Zonal Officers of the Central Drugs Standard Control Organization].
_______
1[FORM 27-E [See Rule 122-F]
Application for grant/renewal* of licence to manufacture blood products for sale or distribution..
1. I/We…………………….of M/s………………………………….hereby apply for the grant of licence/renewal of licence number………..dated………..to manufacture Blood products on the premises situated at ………………………
__________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 245(E) dt 5.4.1994.
267
2. Name(s) of the item(s)
1. 2. 3.
3. The name(s), qualification and experience of competent Technical Staff are as under:
(a) responsible for manufacturing (b) responsible for testing 1. 1. 2. 2. 3. 3.
4. The premises and plant are ready for inspection/will be ready for inspection on……..
5. A licence fee of rupees ……………….and an inspection fee of rupees…………..has been credited to the Government under the Head of Account………………(receipt enclosed)
Signature……………….. Dated………… Name and Designation………….
* Delete whichever is not applicable.
Note :
1. The application shall be accompanied by a plan of the premises, list of machinery and equipment for manufacture of blood products, memorandum of association/constitution of the firm, copies of certificate relating to educational qualifications and experience of the competent technical staff and documents relating to ownership or tenancy of the said premises.
2. A copy of the application together with the relevant enclo sures shall also be sent to the Central Licence Approving Authority and to the Zonal/Sub-Zonal Officers concerned of the Central Drugs Standard Control Organization].
______________
FORM 28 [See Rule 76]
1[Licence to manufacture for sale or for distribution of] drugs specified in Schedules C and C (1)
Number of Licence and date of issue………………………………….
1…………………………………….is hereby licensed to manufacture at the premises situated at the…………………………………………………..the following drugs, being drugs specified in Schedules C and C (1) to the Drugs and Cosmetics Rules, 1945. __________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985
268
Names of drugs……………………………………………
2. Names of approved 1[competent technical staff]……………….
3. The licence authorises the sale by way of wholesale dealing and storage for sale by the licensee of the drugs manufactured under the licence subject to the conditions applicable to licences for sale.
4. The licence wil l be in force from………………………….to………………
5. The licence is subject to the conditions stated below and to such other conditions as may be specified in the Rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date of Issue……………………………. Signature……………….. Designation ……………… 2[*Licensing Authority. * Central Licence Approving Authority.
* Delete whichever is not applicable.
Conditions of Licence
1 This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. If the licensee wants to undertake during the currency of the licence the manufacture for any drug specified in Schedules C and C (1) not in cluded above, he should apply to the Licensing Authority for the necessary endorsement to the licence as provided in Rule 75 (3). This licence will be deemed to extend to the items so endorsed.
3. Any change in the expert staff named in the licence shall be forthwith reported to the Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
____________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 231(E) dt 4.6.1996. 2Subs. by G.O.I. Notification No. GSR 923(E) dt 14.12.1992.
269
FORM 28-A [See Rule 76-A]
Loan1[Licence to manufacture for sale or for distribution of] drugs specified in Schedules C and C (1)
1. Number of licence and date of issue…………………………………….
2………………………………………..of…………………………is hereby granted a loan licence to manufacture on the premises situated at…………………….C/o………………………the following drugs being drugs specified in Schedules C and C (1) to the Drugs and Cosmetics Rules, 1945.
Names of Drugs…………………………………
3. Names of 2[competent technical staff.]……………………………… 33 A The licence shall be in force from…………………………to……………
4. The licence authorizes the sale by way of wholesale dealing by the licensee and storage for sale by the licensee of the drugs manufactured under the licence subject to the conditions applicable to licence for sale.
5. The licence is subject to the conditions stated below and to such other conditions as may be specified in the Rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date of Issue…………………………. Signature………………. Designation……………..
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. If the licensee wishes to undertake during the currency of the licence the manufacture for any drug specified in Schedules C and C (1) not included above, he should apply to the Licensing Authority for the necessary endorsement to the licence as provided in Rule 75 (3). This licence will be deemed to extend to the items so endorsed.
3. Any change in the expert staff named in the licence shall be forthwith reported to the Licensing Authority.
_____________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985 2 Subs. by G.O.I. Notification No. GSR 231(E) dt 4.6.1996. 3 Ins. by G.O.I. Notification No. F.1-10/62-D, dtd 11.4.1964
270
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
______________
1[FORM 28-B [See Rule 76]
2[Licence to manufacture for sale or for distribution of] drugs specified in Schedules C, CI and X.
No. of Licence…………………
1. ……………………….……………. is hereby licensed to manufacture at the premises situated at …………… the following drugs specified in Schedule C, CI and X to the Drugs and Cosmetics Rules, 1945.
Name of drugs.
2. Names of 3[competent technical staff]
3. The licence authorizes the sale by way of wholesale dealing and storage for sale by the licensee of the drugs manufactured under the licence subject to the onditions applicable to licence for sale.
4. The licence shall be in force ……….. to ……………………..
5. The licence is subject to conditions stated below and to other conditions as may be specified in the rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date of issue …………. Signature ………………….. Licence No. …………… Designation………………..
4[*Licensing Authority *Central Licence Approving Authority.
Conditions of Licence 1. The licence and any certificate of renewal in force shall be kept on the approved
premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
____________________________________________________________________________ 1Subs. by G.O.I. Notification No.GSR 462(E) dt 22.6.1982 2Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 3Subs. by G.O.I. Notification No. GSR 231(E) dt 4.6.1996. 4Subs. by G.O.I. Notification No. GSR 923(E) dt 14.2.1992 .
271
2. If the licensee wishes to undertake during the currency of the licence the manufacture of any drug specified in Schedule X not included above, he should apply to the Licensing Authority for the necessary endorsement as provide in Rule 75(4). This licence will be deemed to be applicable to the items so endorsed.
3. Any change in the 1[competent technical staff] shall be forthwith reported to the Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
5. The licensee shall furnish to the Licensing Authority copies of the invoices of sales made to dealers.
6. The licensee shall not manufacture drugs covered by this licence for use as ‘Physician’s Samples’.]
---------------
2[FORM 28-C [See Rule 122-G]
Licence to operate a Blood Bank for collection, storage and processing of whole human blood and/or* its components for sale or distribution
1.Number of licence………………..date of issue……………………at the premises situated at……………..
2. M/s…………………………..is hereby licensed to collect, store, process and distribute while blood and/or its components.
3. Name(s) of the item(s) : 1. 2. 3.
4. Name(s) of the competent Technical Staff : 1. 2. 3.
_________________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 923(E)dt 14.12.1992 2 Ins. by G.O.I. Notification GSR 245(E) dt 5.4.1999.
272
5. The licence authorises licensee to collect, store, distribute and processing of whole blood and/or blood components subject to the conditions applicable to this licence.
6. The licence shall be in force from…………….to………………
7. The licence shall be subject to the conditions stated below and to such other conditions as may be specified from time to time in the Rules made under Drugs and Cosmetics Act, 1940.
Dated :……… Signature………………. Name and Designation………… Licensing Authority Central Licence Approving Authority
* Delete whichever is not applicable.
Conditions of Licence 1. The licensee shall neither collect blood from any professional donor or paid
donor nor shall be prepare blood components from the blood collected from such donor.
2. The licence and any certificate of renewal in force shall be displayed on the approved premises and the original shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
3. any cnange in the technical staff shall be forthwith reported to the Licensing Authority and/or Central Licence Approving Authority.
4. The licensee shall inform the Licensing Authority and/or Central Licence approving Authority in writing in the event of any change in the constitution of the firm operating under the licence, where any change in the constitution of the firm takes places, the current licence shall be deemed to be valid for maximum period of three months from the date on which the change has been taken place unless, in the meantime, a fresh licence has been taken from the Licensing Authority and/or Central Licence approving Authority in the name of the firm with the changed constitution.]
___________
1[FORM 28-D [See Rules 76]
Licence to manufacture for sale of Large Volume Parenterals/Sera and Vaccines specified in Schedules C and C(I)
excluding those specified in Schedule X.
Number of licence………………………and date of issue…………………
___________________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 119(E) dt 11.3.1996.
273
1. …………………is hereby licensed to manufacture at the premises situated at…………………..the following Large Volume Parenterals/Sera and Vaccines specified in Schedules C and C(1) excluding those specified in Schedule X to the Drugs and Cosmetics Rules, 1945.
2. Name(s) of drug(s) ………………………(each item to be separately specified).
3. Name(s) of competent technical staff:
(a) responsible for manufacturing (b) responsible for testing
1. 1. 2 2 3 3
4. The license authorizes the sale by way of wholesale dealing and storage for sale by the licensee of the drugs manufactured under the licence, subject o the conditions applicable to licence for sale.
5. The licence shall be in force from………………………….to……………..
6. The licence shall be subject to the conditions stated below and to such other conditions as shall be specified in the rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Signature ……………… Designation …………………. Licensing Authority Central Licence Approving Authority
Date ……………………..]
Conditions of Licence
1. The licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. If the licensee wishes to undertake during the currency of the licence the manufacture of any drug specified in Schedule X not included above, he should apply to the Licensing Authority for the necessary endorsement as provided in Rule 75(4). This licence will be deemed to be applicable to the items so endorsed.
3. Any change in the competent technical staff shall be forthwith reported to the Licensing Authority. (c) The licensee shall inform the licensing authority and/or Central Licence
Approving Authority in writing in the event of any change in the constitution of the firm operating under the licence, where any change in the constitution of the firm takes place, the current licnece shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been applied
274
for along with prescribed fee and necessary documents to the Licensing Authority and/or Central Licence Approving Authority in the name of the firm with the changed constitution.]
_____________
1[FORM 28-E [See Rule 122-G]
Licence to manufacture and store blood products for sale or distribtion.
1.Number of licence………………..date of issue……………………at the premises situated at……………..
2. M/s…………………………..is hereby licensed to manufacture, store, sell or distribute the following blood products:-
3. Name(s) of the item(s) : 1. 2. 3.
4. Name(s) of the competent Technical Staff : a) responsib le for manufacturing b) responsible for testing 1. 1. 2. 2. 3. 3.
5. The licence authorises licensee to manufacture, sore, sell or distribute the blood products, subject to conditions applicable to this licence.
6. The licence shall be in force from…………….to………………
7. The licence shall be subject to the conditions stated below and to such other conditions as may be specified from time to time in the Rules made under Drugs and Cosmetics Act, 1940.
Dated :……… Signature………………. Name and Designation………… Licensing Authority Central Licence Approving Authority
* Delete whichever is not applicable.
_________________________________________________________________________ 1Ins. by G.O.I. Notification GSR 245(E) dt 5.4.1999.
275
Conditions of Licence 1. The licensee shall not manufacture blood products from the blood drawn from
any professional donor or paid donor. 2. The licence and any certificate of renewal in force shall be displayed on the
approved premises and the original shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
3. Any cnange in the technical staff shall be forthwith reported to the Licensing Authority and/or Central Licence Approving Authority.
4. The licensee shall inform the Licensing Authority and/or Central Licence approving Authority in writing in any change in the constitution of the firm operating under the licence. In the event of any change in the constitution of the firm, the licence shall be deemed to be valid for maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority and/or Central Licence approving Authority in the name of the firm with the changed constitution.]
___________
FORM 29 [See Rule 89]
Licence to manufacture drugs for purposes of examination, test or analysis
1.……………………………….of………………………..is hereby licensed to manufacture the drugs specified below for purposes of examinat ion, test or analysis at………………………………………………………………………………
2. This licence is subject to the conditions prescribed in Part VII of the Drugs and Cosmetics Rules, 1945.
3. This licence shall be in force from one year from date specified below.
Names of drugs
Date………………………………. Licensing Authority……..
______________
FORM 30 [See Rule 90]
Application for licence to manufacture drugs for purposes of examination, test or analysis
I……………………………………………of……………………by occupation............. ………………hereby apply for licence to manufacture the drugs specified below for purposes of examination test or analysis at……………………………… and I undertake to comply with the conditions applicable to the licence.
276
Names of Drugs
Date…………………………. Signature……………………….
________________
FORM 31 [See Rule 139]
Application for grant or renewal of a 1[licence to manufacture cosmetics for sale for distribution.]
1. I / We …………………………of……………….hereby apply for grant / renewal of a licence to manufacture on the premises situated at…………………………..the following cosmetics:-
2. Name of Cosmetics……………………………………………..
3. Names, qualifications and experience of technical staff employed for manufacture and testing……………………………………..
4. A fee of rupees ………………………….has been credited to Government under head of account………………………………………………
Date……………………….. Signature…………………….
Note:—The application should be accompanied by plan of the premises.
2[FORM 31-A [See Rule 138-A]
Application for grant or renewal of loan1[ licence to manufacture cosmetics for sale or for distribution]
1. I / We ……………………………..of…………………..hereby apply for grant / renewal of a loan licence to manufacture cosmetics for sale on the premises situated at…………………………………….C/o…………………………................…….the following cosmetics:--
2. Names of Cosmetics……………………………………….
3. The names, qualifications and experience of the expert shall actually connected with the manufacture and testing of the specified products in the manufacturing premises.
_________________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 788(E) dt 10.10.1985. 2 Ins. by G.O.I. Notification No. GSR 444 dtd 28-4-1973.
277
4. I /We enclose
a) A true copy of a letter from me / us to the manufacture concern whose manufacturing capacity is intended to be utilized by me / us.
b) A true copy of a letter from the 2manufacturing concern that they agree to lend the services of their competent technical staff, equipment and premises for the manufacture of each item required by me / us and that they shall maintain the registers of raw materials and finished products separately in this behalf.
c) Specimen of labels, cartons of the drugs proposed to be manufactured.
5. A fee of Rs…………………………………..has been credited to Government under the head of account………………………………………………..
Date………………………… Signature……………………… ______________
FORM 32 [See Rule 140]
1[Licence to manufacture cosmetics for sale or for distribution]
Number of Licence and date of issue…………………………….
1…………………..is hereby licensed to manufacture on the premises situated at……………………..the following cosmetics under the supervision of the following technical staff:--
a) Names of cosmetics. b) Names of technical staff
2. Enter here the name and address of the manufacturing concern where the manufacture will be actually carried out and also their licence number.
2. The licence shall be in force from…………………………….to…………………….
3. The licence is subject to the conditions stated below and to such other conditions as may be specified in the Drugs and Cosmetics Rules, 1945.
Date………………………….. Signature………………. Designation……………..
_____________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 788 (E) 10.10.1985.
278
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to the Licensing Authority.
3. If the licensee wants to manufacture for sale of additional items he should apply to the Licensing Authority for necessary endorsement to the licence as provided in rule 138 (3). This licence shall be deemed to extend to the cosmetics so endorsed.
14.The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence. Where any change in the constitution of the firm takes place, the current licence shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the form with the changed constitution.
_________________
2FORM 32-A [See Rule 139-B]
Loan 3[Licence to manufacture cosmetics for sale or for distribution]
1. Number of Licence and date of issue
2………………………………..of……………………………..is hereby granted a loan licence to manufacture the following cosmetics on the premises situated at…………………….C/o……………………………………under the direction and personal supervision of the following technical staff: -
a) Names of technical staff. b) Names of cosmetics. 3. The licence shall remain in force from…………………to………….. 4. The licence is subject to the conditions stated below and to such other conditions as
are specified in the rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date……………………… Signature…………… Designation………..
_____________________________________________________________________ 1. 1Ins.by G.O.I. Notification No. S.O. 903 dtd 28-2-1976. 2Ins. by G.O.I. Notification No.GSR 444 dtd 28-4-1973. 3Ins. by G.O.I. Notification No. GSR 788 (E) 10.10.1985.
279
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved premises and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. Any change in the technical staff shall be forthwith reported to the Licensing Authority.
3. If the licensee wants to manufacture for sale additional items he should apply to the Licensing Authority for the necessary endorsement to the licence as provided in rule 138-A (5). This licence shall be deemed to extend to the cosmetics so endorsed.
_____________________
FORM 33 [See Rule 141]
Certificate of renewal of loan licence to manufacture Cosmetics for sale
1. Certified that licence no………………granted on the …………………………to…………………for the manufacture for sale of the following cosmetics at the premises situated at………………has been renewed from…………………..and shall expire on…………………………..
1. Names of cosmetics 2. Names of technical staff
Date………………………… Signature…………………….. Designation…………………..
_________________
1FORM 33-A [See Rule 141-A]
Certificate of renewal of loan licence to manufacture Cosmetic for sale
1. Certified that loan licence No………………granted on the ………………to…………………………for the manufacture for sale of the following cosmetics at the premises situated at C/o…………………………………has been renewed from……………………….to………………….
1. Names of cosmetics. 2. Names of technical staff.
Date………………………… Signature………………….. Designation………………..
_____________________________________________________________________ 1Ins. by G.O.I. Notification No.GSR 444 dtd 28-4-1973.
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FORM 34 [See Rules 131 and 150]
Certificate of test or analysis of cosmetic by the Central Drugs Laboratory or the Government Analyst
1. Name of the officer or Inspector from whom received…………………….. 2. Serial number and date of the Officer’s / Inspector’s
memorandum………………………………………… 3. Number of sample…………………………….. 4. Date of receipt……………………………….. 5. Name of the Cosmetic purporting to be contained in the
sample…………………………………………………………….. 6. Condition of seals on the 1[packet or on portion of sample or container] 7. Results of test or analysis:--
The sample of cosmetics— (a) contains a prescribed colour only
does not contain a prescribed colour.
(b) does not contain harmful ingredients contains harmful ingredients
(c) conforms to claims made on the label as to the nature and quality of the cosmetic does not conform to claims made on the label as to the nature nature and quality of the cosmetic
2[d) contains not more than……………………………….parts per million of Lead and………………………………….parts per million of Arsenic………………………………………….. _______________________________________ contains more than……………………………….. parts per million of Lead and ……………………………….. parts per million of Arsenic.].
Date………………………… Director, Central Drugs Laboratory / Government Analyst
_________________
__________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 59(E) dt 7.2.1995. 2Subs. by G.O.I. Notification No. GSR 510(E) dt 26.7.1982.
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1FORM 35 2[See Rule 65, 67-G, 74, 74A, 74B, 78A, 85H, 142 and 142-A, 158 and 158A]
Form in which the Inspection Book shall be maintained
(A) The cover of the Inspection Book shall contain the following particulars, namely:--
1. The name and address of the Licensee………………………………… 2. Licence number and the date upto which the licence is valid……………………….
(B) (i) The pages of the Inspection Book shall be serially numbered and duly stamped by the Licensing Authority. The pages, other than the first and the last pages, shall have the following particulars:--
Name and designation of the Inspector who inspects the premises of the Licensee:- Date of Inspection……………. Observations of the Inspector…………….
Signature of the Inspector
(ii) The first and last pages of the Inspection Book shall be endorsed by the Licensing Authority with the following words, namely:-- Inspection Book maintained by M/s…………………………… Situated at……………………..for license number……………………………. In Form…………………………………….under the Drugs and Cosmetics Rules.
Seal and Signature of the Licensing Authority
Notes : (i) Printed copy of the Inspection Book may be obtained by the licensee from the Licensing Authority on payment. (ii) The Inspection Book shall be maintained at the premises of the Licensee. (iii) The observations made by the Drug Inspector shall be in triplicate. The original copy shall be retained in the Inspection Book to be maintained in the premises of the Licence. The duplicate copy shall be sent to the Licensing Authority. The triplicate copy shall be taken as record by the Inspector.
___________________________________________________________________________ 1Ins. by G.O.I. Notification No.F.1-14/68-D, dtd 26.10.1968. 2 Subs. by G.O.I. Notification No. GSR 331(E) dt 8.5.1984.
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1FORM 36 [See Rule 150-B]
Application for grant or renewal of approval for carrying out tests on drugs / cosmetics or raw materials used in the manufacture thereof
on behalf of licensees for manufacture for sale of drugs / cosmetics
(1) I / We ………………………………….of………………………………hereby, apply for the grant or renewal of approval for carrying out tests hereby, apply for the grant or renewal of approval for carrying out tests of identity, purity, quality and strength on the following categories of drugs / items of cosmetics or raw materials used in the manufacture thereof on behalf of licensees for manufacture for sale of drugs / cosmetics.
(2) *Categories of drugs, items of cosmetics:-- (a) Drugs other than those specified in Schedule C and C (1) and also excluding
Homoeopathic Drugs:--
1. Crude vegetable drugs. 2. Mechanical contraceptives 3. Surgical dressings 4. Drugs requiring the use of ultravoilet / Infra Red Spectrophotometer
or Chromatography. 5. Disinfectants 6. Other drugs
(b) Drugs specified in Schedule C and C (1):—
1. Sera, Vaccines, Antigens, Toxins, Antitoxins, Toxoids, Bacteriophages and similar Immunological Products.
2. Antibiotics. 3. Vitamins. 4. Parenteral preparations. 5. Sterilized surgical ligature / suture. 6. Drugs requiring the use of animals for their test. 7. Drugs requiring the use of Ultravoilet/ Infra Red/ Spectrophotometer
or Chromatography. 8. Other drugs.
(c) Homoeopathic drugs. (d) Cosmetics
(3) Name, qualifications and experience of expert staff employed for testing and the person-in-charge of testing.
* Delete whichever is not applicable _____________________________________________________________________ 1 Ins.by G.O.I. Notification No.X. 11014/7/76-D&MS, dtd 23-8-1977.
.
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(4) List of testing equipments provided.
(5) I / We enclose a plan of the testing premises showing the location and area of the different sections thereof.
(6) An inspection fee of rupees………………………………….has been credited to Government under Head of Account……………………………
Date……………….. Signature………………
_________________
FORM 37 [See Rule 150-C]
Approval for carrying out tests on drugs / cosmetics and raw materials used in their manufacture on behalf of licensees for manufacture for sale of drugs / cosmetics
Number of approval and date of issue:
(1) Approval is hereby granted to……………………………………..for carrying out tests for identity, purity, quality and strength on the folowing categories of drugs/items of cosmetics and the raw materials used in the manufacture thereof on the premises situated……………………………………………..
Categories of drugs / items of cosmetics
…………………………………………
…………………………………………
…………………………………………
(2) Names of 1[competent technical staff] employed for testing and the person-in- charge of testing.
(3) The approval shall be in force from……………………….to………………
(4) The approval is subject to the conditions stated below and such other conditions as may be specified in the rules for the time being in force under the Act.
Date………………………. Signature……………………… Designation…………………….
_________________________________________________________________________ 1Subs. by G.O.I. Notification No. GSR 231(E) dt 4.6.1996.
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Conditions of Approval
(1) This approval and any certificate of renewal in Form 38 shall be kept in the approved premises and shall be produced at the request of the Inspectors appointed under the Act.
(2) If the approved institution wishes to undertake during the currency of the approval the testing of any other category of drugs or items of cosmetics it should apply to the approving authority for necessary endorsement meant as provided in rule 150-B. This approval will be deemed to extend to the item so endorsed.
(3) Any change in the analytical staff or in the person-in-charge of the testing shall be forthwith to the approving authority.
1[(4) The approved institution shall inform the approving authority in writing in the event of any change of the constitution of the institution operating under this Form. Where any change in the constitution of the institution takes place, the current approval shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless in the meantime, a fresh approval has been taken from the approving authority in the name of the institution with the changed constitution.]
__________________
FORM 38 [See Rule 150-J]
Certificate of renewal of approval for carrying out tests on drugs / cosmetics and raw materials used un the manufacture thereof on behalf of licensees for manufacture for sale of
drugs / cosmetics
(1) Certified that approval number…………………..granted on the …………………………………for carrying out tests of identity, purity, quality and strength on the following categories of drugs / items of cosmetics and the raw materials used in the manufacture thereof at the premises situated at…………………………………………..has been renewed from………………………..to…………………………………………..
Categories of drugs / items of cosmetics
………………………………………..
……………………………………….
(2) Names of 2[competent technical staff] and person-in-charge of testing. …………………………………. ………………………………….
_____________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 681(E) dt 5.12.1980. 2 Subs. by G.O.I. Notification No. GSR 231(E) dt 4.6.1996
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Date…………………… Signature……………….. Designation……………..
--------------------
FORM 39
[See Rule 150-E (f)]
Report of test or analysis by approved institution
(1) Name of the manufacturer from whom sample received together with his manufacturing licence number under the Act and under the Rules made thereunder.
(2) Reference number and date of the letter from the manufacturer under which the sample was forwarded.
(3) Date of receipt of the sample.
(4) Name of drug / cosmetics / raw material / final product in bulk / final product (in finished pack)* as obtained from the manufacturer.
(a) Original manufacturer’s name (in the case of raw materials and drugs repacked). (b) Batch number. 1[(c)Batch size as represented by sample.]. (d) Date of manufacture, if any. (e) Date of expiry, if any.
(6) Results of test or analysis with protocols of test or analysis applied.
In the opinion of the undersigned, the sample referred to above is *of standard quality/is not of standard quality as defined in the Act and the Rules made thereunder for the reasons given below.
Date…………………….. ………………………………….. Signature of Person-in-charge of testing
Note:- Final product includes repacked material. *Delete whichever is not applicable _____________________________________________________________________ .1 Subs. by G.O.I. Notification No.GSR 681(E) dt 6.6.1988.
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*Form 40
[See rule 24-A]
Application for issue of Registration Certification for import of drugs into India under the Drugs and Cosmetics Rules 1945.
I/We_______________________________________________________________ ___________________________ (Name and full address) hereby apply for the grant of Registration Certificate for the manufacturer, M/s. ___________________ (full address with telephone, fax and E-mail address of the foreign manufacturer) for his premises, and manufactured drugs meant for import into India.
1. Names of drugs for registration.
(1)
(2)
(3)
2. I/We enclose herewith the information and undertakings specified in Schedule D (1) and Schedule D (II) duly signed by the manufacturer for grant of Registration Certificate for the premises stated below.
3. A fee of _______________ for registration of premises, the particulars of which are given below, of the manufacturer has been credited to the Government under the Head of Account “0210-Medical and Public Health, 04-Public Health, 104-Fees and Fines under Drugs and Cosmetics Rules, 1945 – Central vide Challan No. ________ dated, (attached in original).
4. A fee of __________________ for registration of the drugs for import as specified at Serial No.2 above has been credited to the Government under the Head of Account “0210-Medical and Public Health, 04-Public Health, 104- Fees and Fines” under the Drugs and Cosmetics Rules, 1945 – Central vide Challan No. _______, dated ___________. (attached original).
5. Particulars of premises to be registered where manufacture is carried on:
___________________________________________________________________ * Ins. by G.O.I. Notification G.S.R. No.604(E) dt. 24-8-2001 w.e.f. 1-1-2003.
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Address (es) ___________________________________________ Telephone No. __________________________________________ Fax __________________________________________ E-mail __________________________________________
I/We undertake to comply with all terms and conditions required to obtain Registration Certificate and to keep it valid during its validity period.
PLACE DATE
Signature __________________ Name ______________________ Designation _________________
Seal/Stamp of manufacturer or his authorized Agent in India.
(Note: - In case the applicant is an authorised agent of the manufacturer in India, the Power of Attorney is to be enclosed).
*Form No. 41 [See rule 27-A]
Registration Certificate
Registration Certificate to be issued for import of drugs into India under Drugs and Cosmetics Rules, 1945.
Registration Certificate No. ____________ Date _____________
M/s ___________________________________ (Name and full address of registered office) ________________________________________________having factory premises at ___________________________________________(full address) has been registered under rule 27-A as a manufacturer and is hereby issued this Registration Certificate.
2. Name (s) of drugs which many be imported under this Registration Certificate: (1) (2) (3)
____________________________________________________________________ * Ins. by G.O.I. Notification G.S.R. No.604(E) dt. 24-8-2001 w.e.f. 1-1-2003
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3. This Registration Certificate shall be in force from __________ to ____________ unless it is sooner suspended or cancelled under the rules.
4. This Registration Certificate is issued through the office of the manufacturer or his authorized agent in India M/s ……………………………… (name and full address) who will be responsible for the business activities of the manufacturer, in India in all respects.
5. This Registration Certificate is subject to the conditions, stated below and to such other conditions as may be specified in the Act and the rules, from time to time.
Place: _________
Date: _________ LICENSING AUTHORITY Seal / Stamp
Conditions of the Registration Certificate.
1. The Registration Certificate shall be displayed at a prominent place by the authorized agent.
2. No drug shall be registered unless it has a free sale approval in the country of origin, and/or in other major countries.
3. The manufacturer or his authorized agent in India shall comply with the conditions of the import licence issued under the Drugs and Cosmetics Rules, 1945.
4. The manufacturer or his authorised agent in India shall inform the licensing authority forthwith in the event of any administrative ac tion taken due to adverse reaction, viz. market withdrawal, regulatory restrictions, or cancellation of authorization, and/or not of standard quality report of any drug pertaining to this Registration Certificate declared by the Regulatory Authority of the country or origin or by any Regulatory Authority of any other country, where the drug is marketed/sold or distributed.
The dispatch and marketing of the drug in such cases shall be stopped immediately, and the licensing authority shall be informed immediately. Further action in respect of such stopped marketing of drug shall be followed as per the direction of the licensing authority. In such cases, action equivalent to that taken with reference to the concerned drug in the country of origin or in the country of marketing shall be followed in India also, in consultation with the licensing authority. The licensing authority may, however, direct any
289
further modification to this course of action, including the withdrawal of the drug from Indian market within 48 hours time period.
5. The manufacturer or his authorized agent in India shall inform the licensing authority within 30 days in writing in the vent of any change in manufacturing process, or in packaging, or in labeling or in testing, or in documentation of any of the drug pertaining to this Registration Certificate.
In such cases, where there shall be any major change/modification in manufacturing or in processing or in testing, or in documentation as the case may be, at the discretion of the licensing authority, the manufacturer or his authorized agent in India shall obtain necessary approval within 30 days by submitting a separate application along with the registration fee, as specified in clause (ii) of sub rule (3) of rule 24-A.
6. The manufacturer or his authorized agent in India shall inform the licensing authority immediately in writing in the event or any change in the constitution of the firm and / or address of the registered office / factory premises operating under this Registration Certificate. Where any such change in the constitution of the firm and/or address takes place, the current Registration Certificate shall be deemed to be valid for a maximum period of three months from the date on which the change has taken place unless, in the meantime, a fresh Registration Certificate has been taken from the licensing authority in the name of the firm with the changed constitution of the firm and/or changed address of the registered office or factory premises.
( Forms 40 to 43 pertaining to Ayurveda, Siddha and Unani drugs replaced by Forms Nos.47 to 50.)
**FORM 44 [See rules 122A, 122B, 122D and 122 DA]
Application for grant of permission to import or manufacture a New Drug or to undertake clinical trial.
I/We …………………………………………………………of M/s. ……………………………….… (address) hereby apply for grant of permission for import and/or clinical trial or for approval to manufacture a new drug or fixed dose combination or subsequent permission for already approved new drug. The necessary information / date is given below :
___________________________________________________________________ **Forms 44 to 46 A inserted as per G.O.I. Notification No.G.S.R.900 (E) dt. 12.12.2001.
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1. Particulars of New Drug : (1) Name of the drug : (2) Dosage Form : (3) Composition of the formulation : (4) Test specification :
(i) active ingredients : (ii)inactive ingredients :
(5) Pharmacological classification of the drug : (6) Indications for which proposed to be used : (7) Manufacturer of the raw material (bulk drug substances) (8) Patent status of the drug.
2. Data submitted along with the application (as per Schedule Y with indexing and page numbers:)
A. Permission to market a new drug :- (1) Chemical and Pharmaceutical information (2) Animal Pharmacology (3) Animal Toxicology (4) Human / Clinical Pharmacology (Phase I) (5) Exploratory Clinical Trials (Phase II) (6) Confirmatory Clinical Trials (Phase III) (including published review articles) (7) Bio-availability, dissolution and stability study Data (8) Regulatory status in other countries (9) Marketing information :
(a) Proposed product monograph (b) Drafts of labels and cartons
(10) Application for test license
B. Subsequent approval / permission for manufacture of already approved new drug : (a) Formulation: (1) Bio-availability / bio-equivalence protocol (2) Name of the investigator/center (3) Source of raw material (bulk drug substances) and stability study data.
(b)Raw material (bulk drug substances) (1) Manufacturing method (2) Quality control parameters and/or analytical specification, stability report. (3) Animal toxicity data.
C. Approval / Permission for fixed dose combination: (1) Therapeutic Justification.
(authentic literature in pre-reviewed journals/text books) (2) Data on pharmacokinetics / pharmacodynamics combination.
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(3) Any other data generated by the applicant on the safety and efficacy of the combination.
D. Subsequent Approval or approval for new indication – new dosage form (1) Number and date of Approval / permission already granted. (2) Therapeutic justification for new claim / modified dosage form (3) Data generated on safety, efficacy and quality parameters.
A total fee of rupees…………………………….(in words)………………….) has been credited to the Government under the Head of Account ………………….(Photocopy of receipt is enclosed).
Dated :….. Signature ……………………. Designation ………….
FORM 45 [See rules 122 A, 122 D and 122 DA]
Permission to import Finished Formulation of the New Drug.
Number of the permission and date of issue ………………………………………………..
M/s. …………………………………………. .of ……………………………………………… (address) is hereby permitted to import the following new drug formulation under rule 122 A / 122 D/ 122 DA of the Drugs and Cosmetics Rules 1945.
(1) Name of the New Drug : (2) Dosage form : (3) Composition : (4) Indications :
Dated ………….. Signature …………………
Name and designation of Licensing Authority …………
Conditions for Grant of Approval / Permission.
(1) The formulation shall conform to the specifications approved by the Licensing Authority.
(2) The proper name of the drug shall be printed or written in indelible ink and shall appear in a more conspicuous manner than the trade name, if any, which shall be shown immediately after or under the proper name on the label of the innermost container of the drug or every other covering in which the container is packed.
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(3) The label of the innermost container of the drug and every other covering in which the container is packed shall bear a conspicuous red vertical line on the left side running throughout the body of the label which shall not be less than 1 mm in width and without disturbing the other conditions printed on the label to depict it is prescription drug.
(4) The label on the immediate container of the drug as well as the packing in which the container is enclosed should contain the following warning: “WARNING : To be sold by retail on the prescription of a …………… Only.”
(5) Post marketing surveillance study shall be conducted during initial period of two years of marketing of the new drug formulation, after getting the protocol and the names of the investigator duly approved by the Licensing Authority.
(6) All reported adverse reactions related to the drug shall be intimated to the Drugs Controller, India and Licensing Authority and regulatory action resulting from their review should be complied with.
(7) No claims except those mentioned above shall be made for the drug without the prior approval of the Licensing Authority.
(8) Specimen of the carton, labels, package insert that will be adopted for marketing the drug in the country shall be got approved from the Licensing Authority before the drugs is marketed.
(9) Each consignment of imported drug shall be accompanied by a test/analysis report.
FORM 45 A [See rules 122 A and 122 DA]
Permission to import raw material (new bulk drug substance)
Number of the permission and date of issue ……………………………………………….
M/s.…………………………………………………….of ……………………….(address) is hereby permitted to import the following raw material (new bulk drug substances) under rule 122 A / 122DA of the Drugs and Cosmetics Rules, 1945, namely :-
Name of the raw material (new bulk drug substances) : (1)…………………………… (2) …………………………… (3)……………………………
Dated ………….. Signature ……………………………..
Name and Designation of the Licensing Authority.
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Conditions for Grant of Approval / Permission
(1) The raw material (new bulk drug substance) shall conform to the test specifications as approved by the Licensing Authority.
(2) For manufacture of raw material (new bulk drug substance) or its formulation in the country, separate approval under rule 122-B shall be obtained from the Licensing Authority.
(3) The permission to import shall not be used to convey or imply that the raw material (new bulk drug) is categorized as “life saving or essential drug.”
FORM 46 [See Rules 122 B, 122 D and 122 DA]
Permission / Approval for manufacture of new drug formulation.
Number of permission and date of issue ………………M/s…………………………… of …………………………………… (address) is hereby granted Permission / Approval to manufacture following new drug formulation under rule 122 B / 122 D / 122 DA of the Drugs and Cosmetics Rules, 1945, namely :-
(1) Name of the formulation: (2) Dosage form: (3) Composition: (4) Indications:
Signature ……………………… Date : …………….. Name and designation of Licensing Authority
Conditions for Grant of Approval / Permission.
(1) The formulation shall conform to the specifications approved by the Licensing Authority.
(2) The proper name of the drug shall be printed or written in indelible ink and shall appear in a more conspicuous manner than the trade name, if any, which shall be shown immediately after or under the proper name on the label of he innermost container of the drug or every other covering in which the container is packed.
(3) The label of the innermost container of the drug and every other covering in which the container is packed shall bear a conspicuous red vertical line on the left side running throughout the body of the label which shall not be less than 1 mm in width and without disturbing the other conditions printed on the label to depict it is prescription drug.
(4) The label on the immediate container of the drug as well s the packing in which the container is enclosed should contain the following warning:
“WARNING : To be sold by retail on the prescription of a ……………. only”
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(5) Post marketing surveillance study shall be conducted during initial period of two years of marketing of the new drug formulation, after getting the protocol and the names of the investigator duly approved by the Licensing Authority.
(6) All reported adverse reactions related to the drug shall be intimated to the Drugs Controller, India and Licensing Authority and regulatory action resulting from their review should be complied with.
(7) No claims except those mentioned above shall be made for the drug without the prior approval of the Licensing Authority.
(8) Specimen of the carton, labels, package insert that will be adopted for marketing the drug in the country shall be got approved from the Licensing Authority before the drug is marketed.
FORM 46 A [See rules 122 B and 122 DA)
Name of the permission / approval and date of issue ………………………………
Permission / Approval for manufacture of raw material (new bulk drug substance) M/s. …………………………of…………………………..(address) is hereby granted
Permission / Approval to manufacture the following raw material (new bulk drug substance) under rule 122 B / 122 DA of the Drugs and Cosmetics Rules, 1945.
Name of the raw material (new bulk drug substance)
(1) ……………………………………………… (2) …………………………………………….. (3) …………………………………………….
Dated ……………………. Signature ………………………… Name and designation of Licensing
Authority ………………………….
Conditions for Grant of Permission / Approval
(1) The raw material (new bulk drug substance) shall conform to the specifications approved by the Licensing Authority.
(2) The raw material (new bulk drug substance) can be sold to only those manufacturers who have permission, in writing, from Licensing Authority, either to use the drug for development purpose/c linical trial-b io-equivalence study or to manufacture the formulation.
(3) For manufacture of the formulation in the country, separate approval under rule 122- B shall be obtained from the Licensing Authority.
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[**FORM 47 [See rule 160 A]
Application for grant or renewal of approval for carrying out tests on Ayurvedic, Siddha and Unani drugs or raw materials used in the manufacture thereof on behalf of licensees for manufacture for sale of Ayurv edic, Siddha and Unani drugs.
(1) *I/We ………………………… of …………………….. hereby apply for the grant / renewal of approval for carrying out tests of identity, purity, quality and strength on the following categories of Ayurvedic Siddha and Unani drugs or raw materials used in the manufacture thereof on behalf of licensee for manufacture for sale of Ayurvedic, Siddha and Unani drugs.
(2)*Categories of Ayurvedic, Siddha and Unani drugs other than those specified in the First schedule to this Act for which testing will be carried out :
AYURVEDA AND SIDDHA UNANI 1. Asava and Arista 1. Nabeez, Khal (Sirka) 2. Arka-Tinir 2. Majoon and its sub-categories
Itrifal, Jawarish, Khameera, Laooq, Halwa
3. Avaleha and Paka-Ilakam 3. Sufoof, Zuroor, Sunoon. 4. Kavatha Curna-Kutinir Curanam 4. Namak, Khar 5. Guggulu . 5. Raughan 6. Ghrita-Ney 6. Zimad 7 Churna-Curanam 7. Habb (Pill) 8. Taila-Tailam 8. Shiyaf 9. Dravaka-Tiravakam 9. Qutoor (drops)
10. Lavana-Uppu 10. Kohal (Surma), Kajal 11. Kshara-Saram 11. Satt, Usara 12. Lepa-Pacai 12. Kushta 13. Vati, Gutika-Kulikai 13. Joshanda (Single drugs) 14. Varti 14. Sharbat Sikanjabeen 15. Netrabindu (Aschyotan) 15. Sayyal, Arq (Distillates) 16. Anjana-Kanmai 16. Qurs (Tablet) 17. Sattva-Sattu 17. Marham, Qairooti 18. Kupipakva Rasayana-Kuppi Centuram 18. Humool, Furzaja 19. Parpati 19. Bakhoor 20. Pishti 20. Nabati Advia 21. Bhasma-Parpam 21. Maadni Advia 22. Mandura-Atai kutinir 22. Asjad Advia
________________________________________________________________________ **Ins. by G.O.I. Notification G.S.R. No.701(E) dt. 27-9-2001 and subs.by G.O.I. Notification No.G.S.R.73(E) dt31.01.2003.
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23. Rasayoga-Centuram 23. Haiwani Advia 24. Lauha 24. Jauhar 25. Ghana Sattva 25. Natool 26. Kvath Pravahi- Kutinir 26. Nashooq,Naswar 27. Panak (Syrup)-Manappaku 27. Shamoom 28. Tablet-Mattirai 28. Saoot (Nasal drops) 29. Capsule 29. Mazoogh 30. Ointment-Kalimapu 30. Tila 31. Phalavarti 31. Lashooq 32. Dhoomravarti/Doopan 32. Gulqand 33. Kshar Sutra/Kshar Varti 33. Fateela 34. Single drugs:
(a) Plant based (b) Mineral based (c) Metal based (d) Animal based (e) Synthetic (f) Any other Ayurvedic, Siddha,
Unani formulation
34. Ghaza, Utban, Sabagh
35. Pushp (Phool) 35. Capsule 36. Nasya 36. Huqna 37. Swarasa (Fresh juice) 37. Naurah 38. Karna Bindu (Ear drops) 38. Latook 39. Any other dosage of patent and
Proprietary and Ayurvedic, Siddha, Unani Drug
39. Vajoor (Throat paint)
40. Mazmazah (Mouth washer)
(3) Names, qualifications experience of experts employed for testing and the person- in-charge of testing.
(4) List of testing equipment provided.
(5) *I/We enclose a plan of the testing premises showing the location and area of the different sections thereof.
(6) An inspection fee of rupees ……………………has been credited to Government under the head of account………………………………………………
Dated ………… Signature …………………..
Full address of the Applicant
*Delete whichever is not applicable.
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[**FORM 48 (See Rule 160 B)
Approval for carrying out tests or analysis on Ayurvedic, Siddha and Unani drugs or raw materials used in the manufacture thereof on behalf of licensees for manufacture
for sale of Ayurvedic, Siddha and Unani drugs.
Number of approval and date of issue:
(1)Approval is hereby granted to ……………………………………….. for carrying out tests in identity, purity, quality and strength on the following categories of Ayurvedic, Siddha or Unani drugs and the raw materials used in the manufacture thereof on the premises situated at …………………………………………………
Categories of Ayurvedic, Siddha and Unani drugs. ………………………………………………………. ………………………………………………………. ………………………………………………………. ……………………………………………………….
(2) Name of experts employed for testing and the person-in-charge of testing …….. ……………………………………………(experts) and …………… (person in charge).
(3)The approval shall be in force from ………………….. to ……………………..
(4)The approval is subject to the conditions stated below and such other conditions as may be specified in the rules for the time being in force under the Act.
Date ………………… Signature ……………………. Place ……………….. Designation ………………….
Seal of State Licensing Authority
Conditions of Approval
(1) The approval and any certificate of renewal in Form 42 shall be displayed in the approved premises and shall be produced in the request of the Inspectors appointed under the Act.
(2) If the applicant wishes to undertake during the currency of the approval the testing of any other category of Ayurvedic, Siddha or Unani drugs it should apply to the approving authority for necessary endorsement as provided in Rule 160A, this approval will be deemed to extend to the items so endorsed.
(3) Any change in the experts or in the person in-charge of the testing shall be forthwith reported to the approving authority.
____________________________________________________________________ ** Ins. by G.O.I. Notification G.S.R. No.702(E) dt. 27-9-2001 and subs.by G.O.I. Notification No.G.S.R.73(E) dt31.01.2003.
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(4) The applicant shall inform the approving authority in writing in the event of any change of the constitution of the laboratory operating under this Form. Where any change in the constitution of the laboratory takes place, the current approval shall be deemed to be valid for a maximum period of three months from the date on which the change takes place unless in the meantime, a fresh approval has been taken from the approving authority in the name of the laboratory with the changed constitution.]
[**Form 49 (See rule 160 I)
Certified of renewal for carrying out tests of analysis on Ayurvedic Siddha or Unani drugs of raw materials used in the manufacture thereof on behalf of licensees for
manufacture for sale of Ayurvedic, Siddha or Unani drugs.
(1) Certified that approval number …………………..granted on the ……… day of…………..2001 for carrying out tests of identity, purity, quality and strength on the following categories of Ayurvedic, Siddha or Unani, dugs and the raw materials used in the manufacture thereof at the premises situated at …………………….. has been renewed from ……………….. to ……………….. (Date).
Catagories of Ayurvedic, Siddha or Unani drugs ……………………………………………………… ………………………………………………………
(2) Names of experts and the person-in-charge of testing ………….(experts) and ………………………………….. (person-in-charge).
Date: …………….. Signature ………………….. Place : …………… Designation ………………
Seal of State Licensing Authority ]
[**FORM 50 (See Rule 160 D(f))
Report of test analysis by approved Laboratory
____________________________________________________________________ ** Ins. by G.O.I. Notification G.S.R. No.701(E) dt. 27-9-2001 and subs.by G.O.I. Notification No.G.S.R.73(E) dt31.01.2003. .
299
(1) Name of manufacturer from which sample received together with his manufacturing license number under the Act or the rules made thereunder, ………………………………………………………………………………………………
(2) Reference number and date of the letter from the manufacturer under which the same was forwarded. ……….……………………………………………………………………………………
(3) Date of receipt of the sample ……………………………………………………………………………………………
(4) Name of Ayurvedic, Siddha and Unani drug of raw material purporting to be contained in the sample. …………………………………………………………………………………………
(5) Details of raw material of final product (in bulk finished pack)* as obtained from the manufacturer:
(a) Original manufacturer’s name in the case of raw materials and drugs packed …………………………………………………………………….
(b) Batch number ………………………………………………….
(c) Batch size as represented by sample……………………………. (d) Date of manufacture, if any …………………………………….
(6)Results of test or analysis with protocols of test or analysis applied or as per Ayurvedic, Siddha or Unani Pharmacopocial standards.
(7) Other specific tests for identity, purity, quality and strength of Patent and Proprietary drugs.
In the opinion of the undersigned, the sample referred to above is of standard *quality / is not standards quality as defined in the Act or the rules made thereunder for the reasons given below ………………………………………………………… ……………………………………
Date : (F.No. ……………………………)
Place : Name & Designation & Seal ………………………… Name & Address of the Laboratory …………………….. Licence No. ………………………………..
Note : Final product includes repacked material. * Delete whichever is not applicable.]
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*“SCHEDULE B” [See rules 7 & 48)
Fees for test or analysis by the Central Drugs Laboratories or State Drugs Laboratories :
1. Fees for test and assay of Drugs requiring use of animals -
Rupees
Adrenocorticotrophic hormone assay 1000 Gonadotrophic hormone for LH activity 1000 FSH Activity 1000 Posterior pituitary extract or its synthetic substitute for oxytocin activity
400
Vasopressor activity 400 Insulin and insulin in combination for hypoglycaemic activity 2000 Hyaluronidase 500 Glucagon 2000 Heparin for anticoagulant activity 600 Protamine sulphate 300 Depressor or Histamine like substane 300 Pyrogen test 500 Antigenecity or foreign protein test 300 Abnormal or undue toxicity or safety test 200 Determination of Lethal doses, LD10 or LD 50 in mice 800 Skin sensitivity/eye irrigation 250 Implantation test 2000
2. Microbiological tests and assays -
Bioassay of Antibiotic 400 Microbiological assay of vitamins 300 Phenol coefficient 300 Preservatives – Microbial challenge test 2000 Sterility test – Parenteral preparations 100 Surgical dressings 200 Syringes and needles 300 Transfusion and infusion sets of assemblies Other sterile devices
400
3. Identification tests -
(a) Chemical Methods 50 ________________________________________________________________________ * Subs. by G.O.I. Notification G.S.R. No.478(E) dt. 7-8-1998.
301
(b) Microscopical 50 (c) IR Spectroscopy 150 (d) (e)
UV Spectroscopy Chromotography
100
(i) Paper (ii) Thin layer (iii) Column (iv) GLC (v) HPCL (vi) Gel Filtration
100 150 100 250 500 300
(f) Electrophoresis
(i) Paper and Cellulose acetate 200 (ii) Polyacrylamide Gel, starch gel, agar gel 300 each
4. Physical tests – (a) Optical rotation, specific gravity, refractive index,
weight per ml, fluorescence. 75 each
(b) Viscocity 100 (c) pH, Solubility, loss on drying, net content, ash, sulphated
ash etc. 20 each
(d) Absorbancy, wt/unit area (surgical), foreign matter, extractive value, thread count etc.
30 each
(e) Uniformity of weight (i) Tablets 15 (i) Capsules 20
(f) Acid value, iodine value, peroxide value, Soponification value, acetyl value.
100 each
(g) Disintegration tests –
(i) Ordinary tablets (ii) Capsule (iii) Sugar Coated tablets (iv) Enteric coated tablets
20 30 50
100
(h) Dissolution test 250 (i) Uniformity of content. 500 (j) Wt. per unit area (powder), particle size, count, methoxy
value. 200 each
(k) Limit test for impurities 100 each (l) Related substances
(i) T LC method (A) Without reference standard (B) With reference standard
150 250
302
(ii) Gas Liquid Chromatography (A) Without reference standard (B) With reference standard
(iii)High pressure Liquid Chromatography (A)Without reference standards (B)With reference standards
250 350
500 500
(m) Water (Karl Fisher) 200
(5) Assays -
(a) General chemical methods 100 for
each ingredient
(b) Non-aqueous/instrumental 200 for
each ingredient
(c) Chromatography (i) TLC (ii) Column (iii) GLC (iv) HPCL (v) Gel filtration
250 200 350 500 400
(d) Nitrogen determination 200 (e) Medicinal gases 400
(6) Polymorph test - (Content of polymorph A in chloramphenicol palmitate) Surgical sutures (Depending on number of test to be carried).. …. 200-500 Other miscellaneous tests 100-500
II Fees for Sera and Vaccine –
Sterility test 100 Abnormal toxicity test 400 Specific toxicity test 800 Inactivation test (Rabies) 200 Potency testing of rabies vaccine 2025 Potency testing of pertussis fraction of DPT vaccine 2025 Potency testing of tetanus fraction of DPT/DT/TT vaccine
2500
Potency testing of diphtheria Fraction of DPT/DT vaccine.
2700
Testing of antisera for the specific titre 1000 Potency testing measles/Mumps/Rubella vaccine 760 each
Testing of Oral Polio Vaccine (OPV) –
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Potency Identity Stability
4550 1000 800
Potency testing of Japanese Encephalitis Vaccine 3900 Potency testing of Snake Venom serum
400 for each venom
Identity testing for vaccines/sera Cell culture (Other than OPV) 400 Other than cell culture 100 Estimation of volume/PH/total solids/No. of organisms/Physical checking.
50 each
Estimation of total proteins/aluminium content/phenol/formaldehyde/thiomersal/moisture. 200 each Pyrogen testing 500 Stability test for vaccines other than Oral Polio Vaccine 4550
III Cosmetics 400 – 1500
(The exact amount of the fee shall be determined by the Director of Laboratory or the Government Analyst, as the case may be).
IV Rubber Condoms 1000
V Homoeopathic medicines: 1. Identification test for raw material of botanical origin
(other than assay of constituents). 125
2. Identification test for raw material of chemical origin (other than assay)
100
3. Limit test for drugs of chemical origin 150 4. Assay of total alkaloids or of drugs of chemical origin 100 5. Identification test for drugs of animal origins or
microbiological. 100
6. Fees for testing of Mother tincture, lower potencies upto 3xor equivalent.
100
7. Determination of Biochemic drug through atomic absorbance spectrophotometer.
75
Note:-1For tests not listed in the Schedule, charges will be determined by the Director or the Government Analyst of the laboratory / institute as the case may be.
2.For the tests relating to Ayurvedic, Unani and Siddha medicines, charges will be determined by the Adviser (Indigenous System of Medicine), Director or Government Analyst of the Laboratory / Institute, as the case may be.
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1SCHEDULE C [See Rules 23, 61 and 76 and Part X)
Biological and Special Products
1. Sera. 2. Solution of serum proteins intended for injection.
23. Vaccines for parenteral injections. 4. Toxins. 5. Antigen. 6. Antitoxins. 7. Neo-arsphenamine and analogous substances used for the specific treatment of
infective diseases. 8. Insulin. 9. Putuitary (Posterior Lobe) Extract.
10. Adrenaline and Solutions of Salts of Adrenaline. 3[11. Antibiotics and preparations thereof in a form to be administered parenterally.] 4[12 Any other preparation which is meant for parenteral administration as such or
after being made up with a solvent or medium or any other sterile product and which-
a) requires to be stored in a refrigerator; or b) does not require to be stored in a refrigerator.]
13. Sterilized surgical ligature and sterilized surgical suture. 14. Bacteriophages.
5[15 Ophthalmic preparations.] 6[16 Sterile Disposable Devices for single use only.]
1. Amended by G.O.I. Notification No. F. 1-30/47-A, dated 5-1-1950 2. Amended by G.O.I. NotificationNo. F. 1-8/60-D, dated 31-8-1960 3. Subs. by G.O.I. Notification No. G.S.R. 487(E) dt 2.7.1984. 4. Amended by G.O.I. Notification No. F. 1-14/68-D, dated 26-10-1968 5. Ins. by G.O.I. Notification No. G.S.R. 1242(E) dt 17.9.1979 6. Ins. by G.O.I. Notification No. G.S.R. 109(E) dt 22.2.1994.
305
1SCHEDULE C (1) [See Rule 23, 61 and 76] Other Special Products
1 Drugs belonging to the Digitalis groups and preparations containing drugs belonging to the Digitalis group not in a form to be administered parentally.
2 Ergot and preparations containing Ergot not in a form to be administered parentally. 3 Adrenaline and preparations containing Adrenaline not in a form to be administered
parenterally. 4 Fish Liver Oil and preparations containing Fish Liver Oil. 5 Vitamins and preparations containing any vitamins not in a form to be administered
parenterally. 6 Liver extract and preparations containing liver extract not in a form to be administered
parenterally. 7 Hormones and preparations containing Hormones not in a form to be administered
parenterally. 8 Vaccine not in a form to be administered parenterally. 2[9 Antibiotics and preparations thereof not in a form to be administered parenterally.] 5[10 In-vitro Blood Grouping Sera.
11 In-vitro diagnostic Devices for HIV, HbsAg and HCV.]
SCHEDULE D
[See Rule 43]
Class of drugs Extent and conditions of exemption
1. Substances not intended for medicinal use
All provisions of Chapter III of the Act and Rules thereunder subject to the conditions that if the substance is imported in bulk, the importer shall certify that the substance is imported for non-medicinal uses, and if imported otherwise than in bulk, each container shall bear a label indicating that the substance is not intended for medicinal use or is intended for some purposes other than medicinal use or is intended for some purposes other than medicinal use or is of commercial quality.
2. 3[* * *] 3. 3[* * *] 4. 4[* * *]
1Amended under G.O.I. Notification No. F. 1-22/59-D, dated 9-4-1960 2Subs. by G.O.I. Notification No.G.S.R.487(E) dt 2-7-1984. 3Entry 2 and 3 of Schedule D omitted by G.O.I. Notification No. F.1-6/62-D dt 2-7-1969 4Entry 4 of Schedule D omitted as per GOI Notification No.604 (E) dt 24-8-2001 5 Ins by G.O.I. Notification No G,S,R, 600(E) dt 27.08.2002.
306
Class of drugs Extent and conditions of exemption 5. The following substances, which
are used both as articles of food as well as drugs: --
All provisions of Chapter III of the Act and Rules there under.
i)
ii)
iii)
iv)
All condensed or powered milk whether pure, skimmed or malted, fortified with vitamins and minerals. Farex, Oats, Lactose and all
other similar cereal preparations whether fortified with vitamins or otherwise excepting those for parenteral use. Virol, Bovril, Chicken essence and all other similar predigested food.
Ginger, Pepper, Cumin, Cinnamon and all other similar spices and condiments unless they are specifically labelled as conform - ing to the standards in the Indian Pharmacopoeia or the official pharmacopoeias and the official compendia of the drug standards prescribed under the Act and Rules made thereunder.
**SCHEDULE D (I). [See rule 21 (d) and rule 24 A]
Information and undertaking required to be submitted by the manufacturer or his authorized agent with the Application Form for Registration Certificate. The format shall be properly filled in for each application in Form 40. The detailed information, secret in nature, may be furnished on a Computer Floppy.
1. Particulars of the manufacturer and manufacturing premises 1.1 Name and address f the manufacturing premises (Telephone No.,
Fax No.,E- mail address) to be registered. 1.2 Name (s) and address (es) of the Proprietor /ProprietorS /Partners / Directors. 1.3 Name and address of the authorized Agent in India, responsible for
the business of the manufacturer.
** Ins. by G.O.I. Notification G.S.R. No.604(E) dt 24-8-2001 w.e.f. 1-1-2003,
307
1.4 A brief profile of the manufacturer’s business activity, in domestic as well as global market.
1.5 A copy of Plant Master File (duly notarised)
1.6 A copy of Plant Registration / approval Certificate issued by the Ministry of Health/National Regulatory Authority of the foreign country concerned (duly notarised)
1.7 A brief profile of the manufacturer’s research activity.
2. Particulars of the manufactured drugs to be registered under Registration Certificate.
a. Name of drugs (Bulk/Formulations/Special product) to be registered meant for import into and use in India.
b. A copy of the approved list showing the bulk drugs/formulations/special products mentioned in 2.1 above are permitted for manufacturing / marketing in the country of origin, (duly notarized)
c. A copy of Good Manufacturing Practice (GMP) certificate, as per WHO- GMP guidelines, or Certificate of Pharmaceutical Products (CPP), issued by the National Regulatory Authority of the foreign country concerned, in relation to the bulk drugs or formulations or special products, meant for import into India.
d. The domestic prices of the drugs to be registered in India, in the currency of the country of origin.
e. The name(s) of the drugs which are original research products of the manufacturer.
3.Undertaking to declare that: -
3.1. We shall comply with all the conditions imposed on the Registration Certificate, read with rules 74 and 78 of the Drugs and Cosmetics rules, 1945.
3.2 We declare that we are carrying on the manufacture of the drugs mentioned in this Schedule, at the premises specified above, and we shall from time to time report any change of premises on which manufacture will be carried on and in the cases where manufacture is carried on in more than one factory any change in the distribution of functions between the factories.
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3.3 We shall comply with the provisions of Part IX of the Drugs and Cosmetics Rules, 1945.
3.4 Every drug manufactured by us for import under the Registration Certificate into India shall be as regard strength, quality and purity conforms with the provisions of Chapter III of Drugs and Cosmetics Act, 1940 and Part IV of the Drugs and Cosmetics Rules 1945, and their amendments from time to time.
3.5 We shall from time to time report for any change or manufacturing process, or in packaging, or in labeling, or in testing, or in documentation of any of the drugs, pertaining to the Registration Certificate, to be granted to us. Where any change in respect of any of the drugs under the Registration Certificate has taken place in respect of any of the above matters, we shall inform the same to the licensing authority in writing within 30 days from the date of such changes. In such cases, where there will be any major change/modification in manufacturing or in processing or in testing, or in documentation, as the case may be, at the discretion of the licensing authority, we shall obtain necessary approval within 30 days by submitting a separate applic ation, alongwith the registration fee as specified in clause (ii) of sub rule (3) of rule 24-A.
3.6 We shall from time to time report for any administrative action taken due to adverse reaction, viz. market withdrawal regulatory restriction, or cancellation of authorization and/or “not of standard quality report” of any drug pertaining to the Registration Certificate declared by any Regulatory Authority of any country where the drug is marketed/sold or distributed. The despatch and marketing of the drug in such cases, shall be stopped immediately and the licensing authority shall be informed immediately. Further action in respect of stop marketing of drug shall be taken as per the directions of the licensing authority. In such cases, action equivalent to that taken with reference to the concerned drug(s) in the country of origin or in the country of marketing will be followed in India also, in consultation with the licensing authority. The licensing authority may direct any further modification to this course of action, including the withdrawal of the drug from Indian market within 48 hours time period.
3.7 We shall comply with such further requirements, if any, as may be specified, by the Government of India, under the Act and the rules made there under.
3.8 We shall allow the licensing authority and/or any person authorized by him in that behalf to enter and inspect the manufacturing premises and to examine the process/procedure and documents in respect of any drug manufactured by us for which the application for Registration Certificate has been made.
3.9 We shall allow the licensing authority or any person authorized by him in that behalf to take samples of the drugs concerned for test, analysis or examination, if considered necessary by the licensing authority.
309
Place: Date:
Signature of the manufacturer Seal / Stamp
**SCHEDULE D (II) (See rule 21 (d) and rule 24 A)
Information required to be submitted by the manufacturer or his authorized agent with the Application Form for the registration of a bulk drug/formulation/special product for its import into India. The format shall be properly filled in and the detailed information, secret in nature, may be furnished on a Computer Floppy.
1. GENERAL
1.1. Name of the drug/formulation/special product, a brief description and the therapeutic class to which it belongs.
1.2. Regulatory status of the drug. Free Sale Certificate and/or Certificate of Pharmaceutical Products (CPP) issued by the Regulatory Authority of the country of origin. Free sale approval issued by the Regulatory Authorities of other major countries.
1.3. Drugs Master File (DMF) for the drug to be registered (duly notarised).
1.4. GMP Certificate in WHO formats or Certificate of Pharmaceutical Products (CPP) issued by National Regulatory Authority of the country of origin (duly notarised).
1.5. List of countries where marketing authorization or import permission for the said drug is granted with date (respective authorisation shall be enclosed).
1.6. List of countries where marketing authorisation or import permission for the said drug is cancelled/withdrawn with date.
1.7. List of countries where marketing authorisation or import permission for the said drug is pending since (date).
1.8. Domestic price of the drug in the currency followed in the country of origin.
1.9. List of countries where the said drug is patented.
_________________________________________________________ ** Ins. by G.O.I. Notification G.S.R. No.604(E) dt 24-8-2001 w.e.f. 1-1-2003,
310
2. CHEMICAL AND PHARMACEUTICAL INFORMATION OF DRUGS.
2.1 Chemical name. Code name or number, if any Non-proprietory or generic name, if any Structure Physico-chemical properties.
2.2 Dosage form and its composition. Qualitative and Quantitative composition in terms of the active substances(s) and excipient(s)
List of active substance(s) separately from the constituent(s) of excipients.
2.3 Specifications of active and inactive ingredient (s) including pharmacopoeal references.
2.4 Source of active ingredient(s), name and address.
2.5 Tests for identification of the active ingredient(s),
Method of its assays and tests for impurity profile with reference standards for the impurities (Protocol to be submitted alongwith reference standards for the impurities / relative substances).
2.6 Outline method and flow chart of manufacture of the bulk drug or finished formulation or special product.
2.7 Detailed test protocol for the drug with pharmacopoeal reference or in- house specification as approved by the registration authority, in the country of origin.
2.8 Stability data including accelerated stability and real time stability analysis.
2.9 Documentation on pack size.
2.10 Numerical expression on EAN bar code on the labels and cartons,
2.11 Safety documents on conta iners and closures.
2.12 Documentation on storage conditions.
2.13 Three samples of medicinal product/drug and outlet packing are to be submitted with batch certificates. Additional samples as well as reference substances with batch certificates including date of manufacture, shelf life, and storage conditions of reference substance may be required both during
311
registration procedure and during validity of registration decision.
2.14 Batch test reports/certificate of five consecutive production batches in details of the medicinal product are to be submitted for every site of manufacturing premises.
2.15 Manner of labeling as per rule 96 of the Drugs and Cosmetics Rules 1945.
2.16 Package insert.
2.17 Details of safety handling procedure of the drug.
2.18 Details of PMS study report for marketing period not exceeding five years .
3. BIOLOGICAL AND BIOPHARMACEUTICAL INFORMATION OF DRUGS.
3.1 Biological control tests applied on the starting material, if applicable.
3.2 Biological control tests applied on the intermediate products, if applicable.
3.3 Biological control tests applied on the finished medical products, if applicable.
3.4 Stability of the finished products in terms of biological potency of the drug, if applicable.
3.5 Sterility tests, if applicable, specification and protocol therein.
3.6 Pyrogen tests, if applicable, specification and protocol therein.
3.7 Acute and sub-acute toxicity tests, if applicable specification and protocol therein.
3.8 Bio-availability studies and bio-equivalence data, if applicable.
3.9 Data relating to the environmental risk assessment for r-DNA products.
3.10 Other information relevant under the section.
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4. PHARMACOLOGICAL AND TOXICOLOGICAL INFORMATION OF DRUGS.
Executive summary of the product is to be submitted mentioning the specific and general pharmacological actions of the drug and pharmacokinetic studies on absorption, metabolism, distribution and excretion. A separate note is to be given on acute and sub-acute toxicity studies and long term toxicity studies. Specific studies on reproductive toxicity, local toxicity and carcinogenic activity of the drug is to be elaborated, as far as possible.
5 CLINICAL DOCUMENTATION
A new drug as defined under rule 122-E of the Drugs and Cosmetics Rules, 1945 is required to be permitted separately by the licensing authority under rule 122-A of the said rules prior to its registration. Such a new drug requires a brief summary and clinical documentation, alongwith permission under 122-A of the said rules for its Registration Certificate.
6. LABELLING AND PACKAGING INFORMATION OF DRUGS.
6.1 Labels should conform as per the specifications under the Drugs and Cosmetics Rules 1945.
6.2 Package insert should be in English and shall indic ate the following therapeutic indications: - Posology and method of administration . Contra-indications. Special warnings and special precautions for use, if any. Interaction with other medicaments and other forms of interaction. Pregnancy and lac tation, if contra-indicated. Effects on ability to drive and use machines, if contra-indicated. Undesirable effects/side effects. Antidote for overdosing.
6.3 Package insert should indicate the following pharmaceutical information: -
List of excipients Incompatibilities Shelf life in the medical product as packaged for sale. Shelf life after dilution or reconstitution according to direction. Shelf life after first opening the container. Special precautions for storage. Nature and specification of the container. Instructions for use/handling.
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7 SPECIFIC INFORMATION REQUIRED FOR THE SPECIAL PRODUCTS (to be supplied, separately in annexure, as ‘A’, ‘B’ and ‘C’)
The information submitted above is true to the best of my knowledge and belief.
Place Date Signature of the manufacturer
Seal/Stamp
NB: 1. Any change in the process of manufacture, method of testing, labeling, packing, designing of the sale pack, medical literature and documentation is to be intimated to the licensing authority forthwith and permission to be obtained from him within 30 days time period.
2. Information relating to Serial No.4 and Serial No.5 are not applicable for drugs figuring in Indian Pharmacopoeia and also for the drugs figuring in United States of Pharmacopoeia, European Pharmacopoeia, and British Pharmacopoeia provided such drugs have already been approved for marketing in India for the applicant under rules 122A, 122B, 122C or 122D of the Drugs and Cosmetics Rules 1945.
ANNEXURE-A (See Schedule D-II, item No.7)
INFORMATION TO BE SUBMITTED IN SCHEDULE D-II
SPECIFIC INFORMATION REQUIRED FOR THE BLOOD PRODUCTS.
A product dossier showing the: -
1. Details of source Plasma, its viral screening, storage and transport from Collection Centres to Fractionation Centre. Regulatory status of Collection Centres.
2. Details of Fractionation Centre, Regulatory Status, Method of Fractionation and Control Processes.
3. Details of viral inactivation process for enveloped and non-enveloped virus(es) and viral validation studies to assess the viral load of the product. Testing of viral screening at any stage is to be high lighted with the details of the kits used with their respective sensit ivity and specificity.
4. Bulk filtration prior to pharmaceutical packing giving the full details of Micro- filtration or nanofiltration followed.
5. Complete details of pharmaceutical processing and utilization.
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6. Test protocol of the product showing the specification and pharmacopoeia method followed for various testing parameters. Specific batch test report for at least 3 batches showing the specifications of each testing parameter.
7. Pack size and labeling.
8. Product insert.
9
.
Specimen Batch Release Certificate issued by the National Regulatory Authority of the country of origin. Specific processings like safe handling, material control, area control, pasteurization, stability studies, storage at quarantine stage and finished stage and packaging should be highlighted in the product dossier.
The information submitted above is true to the best of my knowledge and belief.
Place:
Date: Signature of the manufacturer Seal / Stamp
NB: 1. Any change in the process of manufacture, method of testing, labeling, packing, designing of the sale pack, medical literature and documentation is to be intimated to the licensing authority forthwith and permission to be obtained from him within 30 days time period.
ANNEXURE-B (See Schedule D-II, item No.7)
INFORMATION TO BE SUBMITTED IN SCHEDULE D-II SPECIFIC INFORMATION REQUIRED FOR THE DIAGNOSTIC KITS.
A product dossier showing the :-
1. The details of source antigen or antibody as the case may be and characterization of the same. Process control of coating of antigen or antibody on the base material like Nitrocellulose paper, strips or cards or ELISA wells etc.
Details of composition of the kit and manufacturing flow chart process of the kit showing the specific flow diagram of individual components or source of the individual components.
2. Test protocol of the kit showing the specifications and method of testing.
315
In house evaluation report of sensitivity, specific ity and stability studies carried out by the manufacturer.
3. The report of evaluation in details conducted by the National Control Authority of country of origin.
Specimen batch test report for at least consecutive 3 batches showing specification of each testing parameter.
4. The detailed test report of all the components used/packed in the finished kit.
5. Pack size and labeling.
6. Product insert.
Specific evaluation report, if done by any laboratory in India, showing the sensitivity and specificity of the kit.
Specific processing like safe handling, material control, area control, process control, stability studies, storage at quarantine stage and finished stage, packaging should be highlighted in the product dossier.
The information submitted above is true to the best of my knowledge and belief.
Place:
Date: Signature of the manufacturer Seal / Stamp
NB: 1. Any change in the process of manufacture, method of testing, labeling, packaging, designing of the sale pack, medical literature and documentation is to be intimated to the licensing authority forthwith and permission to be obtained from him within 30 days time period.
ANNEXURE-C (See Schedule D-II, item No.7)
INFORMATION TO BE SUBMITTED IN SCHEDULE D-II SPECIFIC INFORMATION REQUIRED FOR VACCINES.
A product dossier showing the: -
1. History, source, date of receipt, storage, identity and characterization of the seed strain.
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2. Detailed flow chart of manufacturing process showing al the details of inprocess control on toxicity, potency study and stability data of the final bulk and the final finished product including the storage temperature.
3. Complete details of chemical and pharmaceutical data for the product.
Composition and dosage form – method of manufacture with detailed flow chart – control of starting material – control tests on intermediate and finished products – certificate of analysis of finished products – validation of critical manufacturing steps.
4. Test protocol of the vaccines showing the specification and method of testing including pharmacopoeal specification.
5. Specimen batch test report for at least consecutive three batches showing the specification of each testing parameter.
6. The detailed test reports of all the components used / packed in the finished vaccine.
7. Pack-size and labelling. 8. Product insert 9. Specimen batch release certificates issued by the National Regulatory Authority
of the country of origin. 10. Summary of pre-clinical and clinical data including :
(a)Prescribing information.
(b) Pharmacological and toxicological data pertaining to tests on animals Characterisation of immune response and safety study in human use, in specific conditions.
Specific information on source of seed strain, its characterization, inactivation, etc. and processings like safe handling, material control area control, process control, stability studies, storage at quarantine stage and finished state, packing should be highlighted in the product dossier.
Specimen production and quality control protocols for at least three consecutive lots showing the specifications for each quality control parameter including pharmacopoeial requirement shall be submitted for study.
The information submitted above is true to the best of my knowledge and belief.
Place Signature of the manufacturer Date: Seal / Stamp
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NB: 1. Any change in the process of manufacture, method of testing, labelling, packaging, designing of the sale pack, medical literature and documentation is to be intimated to the licensing authority forthwith and permission to be obtained from him within 30 days time period.
2. All vaccines shall be new drugs unless certified otherwise by the liencesing authority approved under Rule 21 of the Drugs and Cosmetic Rules, 1945. A copy of approval of the vaccine issued by the said licensing authority is to be enclosed, prior to issue of Registration Certificate of the said vaccines.
SCHEDULE E [Omitted as per GOI Notification No.G.S.R. 462(E) dt 22-6-1982]
*[SCHEDULE E (1) [See Rule 161 (2)]
List of poisonous substances under the Ayurvedic (including Siddha) and Unani Systems of Medicine
A. AYURVEDIC SYSTEM I Drugs of vegetable origin
Ahipena Papaver somniferum Linn. Arka Calotropis gigantea (linn.)R. Br. ex. Ait. Bhallataka Semecarpus anacardium Linn. F Bhanga Cannabia eativa Linn. Danti Baliospermum monatanum Mull. Arg Dhattura Datura metal Linn.. Gunj Abrus precatirius Linn. Jaipala (Jayapala) Croton tiglium Linn Karaveera Rerium indicum Mill Langali Gloriosa superba Linn Parasika Yavani Hyoseyamus inibar Linn Snuhi Euphorbia neriifolia Linn Vatsanabha Acontium Chasmanthum Stapfex Holm Vishamushti Strychnox nuxvomica Linn. Shringivisha Acontium chasmanthum Stapfex Holm.
II Drugs of Animal Origin . Sarpa Visha Snake poison
III Drugs of Mineral Origin Gauripashana Arsenic Hartala Arseno sulphide Manahashila Arseno sulphide Parada Mercury Rasa Karpura Hydrargyri subchloridum Tuttha Copper sulphate Hingula Cinnabar
________________________________________________________________ * Added under G.O.I. Notification No. 1-23/67-D dated 2-2-1970
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Sindura Red oxide of lead Girisindura Red oxide of mercury
B. SIDDHA SYSTEM
Abini Papaver Somniferum Linn. Alari Nerium indicum Mill. Azhavanam Lawsonia inermis Linn. Attru thummatti Citrullis colocynthis Scharad. Anai Kunri Adanathera pavonina Linn. Rattha Polam Aloe barbadensis Mill. Ilaikalli Euphorbia neriifolia Linn. Eezhaththalari Plumeria acuminota Ait. Gomatthai Datrua stramonium Linn. Etti Strychnos nuxvomica Linn. Ganja Cannabis sativa Linn. Kalappaik Kizhangu Gloriosa superba Linn. Kodikkalli Euphorbia tiruqalli Linn. Chadurakkalli Euphorbia antiquorium Linn. Karia polam Aloe sp. Kattamanakku Jatropha glandulifera Roxb. Kattu thumatti Cucmis trigonus Roxb . Kunri Abrus precotorusu Linn. Cheran Kottai Semicorpus anacardium Linn. Thillai Exoecoria agallocha Linn. Nabi Aconitum ferox Wall. Nervalam Croton tiglium Linn. Pugai Elai Nicotiana tobucum Linn. Marukkarai Randia dumetorum Lam. Mansevikkalli Euphorbia sp.
C. UNANI SYSTEM
I Drugs of vegetable origin
Afiyun Papaver somniferum Linn. Bazrul-banj Hyoscyamus niger Linn Bish Aconitum chasmanthum Strapfex Holmes Bhang Cannabis sativa Linn. Charas Canabis sativa Linn Dhatura seeds Datura metal Linn (seeds) Kuchla Strychnos nuxvomica Linn Shokran Conium maculatum Linn
II Drugs of Animal origin
Sanp (head) Snake (head)
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Telni makkhi Mylabris cichori Linn Mylabaris pustulataThund Mylabris macilenta
III Drugs of Mineral origin
Darchikna Hydrargryi perchloridum Hira Diamond Ras Kapoor Hydrargryi Subchloridum (calomel) Shingruf Hydrargryi bisulphuratum Zangar Cupri subacetas Sammul-Far (Abyaz, Asfar, Aswad and Ahmar)
Arsenic (white, yellow, black and red)
Tootiya Copper Sulphate Para Hydrargyrum Hartal Arsenic trisulphide (yellow)
_________________________
SCHEDULE F
Part I – Omitted as per G.O.I. Notification GSR 663(E) dt 3-7-1992 and corrected as per GOI Notification No. GSR 27 (E) dt 22-1-1993.
Part II, Part III, Part IV, Part V, Part VI, Part VII, Part VIII, Part IX, Part X, Part X, Part XI, Part XII and Part XII-A omitted as per G.O.I. Notification No. GSR 663(E) dt 3-7- 1992.
____________________________________________
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1PART XII B REQUIREMENTS FOR THE FUNCTIONING AND OPERATION OF A BLOOD BANK
AND / OR FOR PREPARATION OF BLOOD COMPONENTS. BLOOD BANKS / BLOOD COMPONENTS.
A. GENERAL 1. Location and Surroundings : The blood bank shall be located at a place which
shall be away from open sewage, drain, public lavatory or similar unhygienic surroundings.
2. Building : The building (s) used for operation of a blood bank and/or preparation of blood components shall be constructed in such a manner so as to permit the operation of the blood bank and preparation of blood components under hygienic conditions and shall avoid the entry of insects, rodents and flies. It shall be well lighted, ventilated and screened (mesh), wherever necessary. The walls and floors of the rooms, where collection of blood or preparation of blood components or blood products is carried out shall be smooth, washable and capable of being kept clean. Drains shall be adequate size and where connected directly to a sewer, shall be equipped with traps to prevent back siphonage.
3. Health, clothing and sanitation of staff: The employees shall be free from contagious or infectious diseases. They shall be provided with clean overalls, headgears, foot-wears and gloves, wherever required. There shall be adequate, clean and convenient hand washing and toilet facilities.
B. ACCOMMODATION FOR A BLOOD BANK.
A blood bank shall have an area of 100 square meters for its operations and an additional area of 50 square meters for preparation of blood components. It shall be consisting of a room each for –
(1) Registration and medical examination with adequate furniture and facilities for registration and selection of donors;
(2) Blood collection (air-conditioned);
(3) Blood component preparation. (This shall be air-conditioned to maintain temperature between 20 degree centigrade to 25 degree centigrade);
___________________________________________________________________ 1Schedule “M” substituted by G.O.I. Notification G.S.R. No.245(E) dtd 05.04.1999.
(4) Laboratory for blood group serology. (air -conditioned);
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(5) Laboratory for blood transmissible diseases like Hepatitis, Syphilis, Malaria, HIV-antibodies (air-conditioned);
(6) Sterilization-cum-washing; (7) Refreshment-cum-rest room (air-conditioned);
(8) Store-cum-records.
NOTES :
(1) The above requirements as to accommodation and area may be relaxed, in respect of testing laboratories and sterilization-cum-washing room, for reasons to be recorded in writing by the Licensing Authority and/or the Central Licence Approving Authority, in respect of blood banks operating in hospitals, provided the hospital concerned has a pathological laboratory and a sterilization-cum-washing room common with other departments in the said hospital.
(2) Refreshments to the donor after phlebotomy shall be served so that he is kept under observation in the Blood Bank.
C PERSONNEL
Every blood bank shall have following categories of whole time component technical staff:-
(a) Medical Officer, possessing the qualification specified in condition (i) of rule 122-G.
(b) Blood Bank Technician(s) possessing – (i) Degree in Medical Laboratory Technology (M.L.T) with six months experience in the testing of blood and/or its components; or
(ii) Diploma in Medical Laboratory Technology (M.L.T) with one year’s experience in the testing of blood and / or its components. the degree or diploma being from a University / Institution recognized by the Central Government or State Government.
(c) Registered Nurse(s); (d) Technical supervisor (where blood components are manufactured), possessing-
(i) Degree in Medical Laboratory Technology (M.L.T) with six month’s experience in the preparation of blood components; or (ii) Diploma in Medical Laboratory Technology (M.L.T) with one year’s experience in the preparation of blood components the degree or diploma being from a University / Institution recognized by the Central Government or State Government.
.
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NOTES :
(1) The requirements of qualification and experience in respect of Technical Supervisor and Blood Bank Technician shall ap ply in the cases of persons who are approved by the Licensing Authority and / or Central Licence Approving Authority after the commencement of the Drugs and Cosmetics (Amendment) Rules, 1999.
(2) As regards the number of whole time competent technical personnel, the blood bank shall comply with the requirements laid down in the Directorate General of Health Services Manual.
3) It shall be the responsibility of the licensee to ensure through maintenance of records and other latest techniques used in blo od banking system that the personnel involved in blood banking activities for collection, storage, testing and distribution are adequately trained in the current Good Manufacturing Practices/Standard Operating Procedures for the tasks undertaken by each personnel. The personnel shall be made aware of the principles of Good Manufacturing Practices / Standard Operating Procedures that affect them and receive initial and continuing training relevant to their needs.
D. MAINTENANCE
The premises shall be main tained in a clean and proper manner to ensure adequate cleaning and maintenance of proper operations, the facilities shall include:- (1) Privacy and thorough examination of individuals to determine their suitability
as donors. (2) Collection of blood from donors with minimal risk of contamination of
exposure to activities and equipment unrelated to blood collection. (3) Storage of blood or blood components pending completion of tests. (4) Provision for quarantine, storage of blood and blood components in a
designated location, pending repetition of those tests that initially give questionable serological results.
(5) Provision for quarantine, storage, handling and disposal of products and regarding not suitable for use.
(6) Storage of finished products prior to distribution or issue.
(7) Proper collection, processing, compatibility testing, storage and distribution of blood and blood components to prevent contamination.
(8) Adequate and proper performance of all procedures relating to plasmapheresis, plateletpheresis and leucapheresis.
(9) Proper conduct of all packaging, labeling and other finishing operations.
(10) Provision for sale and sanitary disposal of :
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(i) Blood and/or blood components not suitable for use, distribution or sale.
(ii) Trash and items used during the collection, processing and compatibility testing of blood and / or blood components.
E. EQUIPMENT.
Equipment used in the collection, processing, testing, storage and sale/distribution of blood and is components shall be maintained in a clean and proper manner and so placed as to facilitate cleaning and maintenance. The equipment shall be observed, standardized and calibrated on a regularly scheduled basis as described in the Standard Operating Procedures Manual and shall operate in the manner for which it was designed so as to ensure compliance with the official requirements (the equipments) as stated below for blood and its components.
Equipment that shall be observed, standardized and calibrated with at least the following frequencies:
EQUIPMENT PERFORMANCE FREQUENCY FREQUENCY OF CALIBRATION
1. Temperature Recorder
Compare against thermometer
Daily As often as necessary
2 Refrigerated centrifuge
Observe speed and temperature
Each day of use
As often as necessary
3 Hematocrit centrifuge
-- -- Standardise before initial use, after repair or adjustments and annually.
4, General lab. -- -- Tachometer, every 6 months.
5. Automated Blood typing,
Observe controls for correct results
Each day of use
--
6. Haemoglobinometer Standardize against cyanamethemoglobulin standard
Each day of use.
--
7. Refractiometer or Urinometer
Standardize against distilled water
-- ditto -- --
8. Blood container Standardize against -- ditto -- As often as
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weighing device container of known weight.
necessary
9 Water Bath Observe temperature -- ditto -- -- d itto--
10 Rh view box (wherever necessary)
-- ditto -- -- ditto -- -- d itto --
11 Autoclave -- d itto-- Each time of use.
-- d itto--
12 Serologic rotators Observe controls for correct results
Each day of use
Speed as often as necessary.
13 Laboratory thermometers -- --
Before initial use
14 Electronic thermometers -- Monthly --
15 Blood agitator Observe weight of the first container of blood filled for correct results
Each day of use
Standardize with container of known mass or value before initial use, and after repairs or adjustments.
F. SUPPLIES AND REAGENTS:
All supplies and reagents used in the collection, processing, compatibility, testing, storage and distribution of blood and blood components shall be stored at proper temperature in a safe and hygienic place, in a proper manner and in particular –
(a) all supplies coming in contact with blood and blood components intended for transfusion shall be sterile, pyrogen-free, and shall not interact with the product in such a manner as to have an adverse effect upon the safety, purity, potency or effectiveness of the product.
(b) supplies and reagents that do not bear an expiry date shall be stored in a manner that the oldest is used first.
(c) supplies and reagents shall be used in a manner consis tent with instructions provided by the manufacturer.
(d) all final containers and closures for blood and blood components not intended for transfusion shall be clean and free of surface solids and other contaminants.
(e) each blood collecting container and its satellite container(s), if any, shall be examined
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visually for damage or evidence of contamination prior to its use and immediately after filling. Such examination shall include inspection for breakage of seals, when indicated, and abnormal discoloration. Where any defect is observed, the container shall not be used, or if detected after filling, shall be properly discarded.
(f) representative samples of each lot of the following reagents and/or solutions shall be tested regularly on a scheduled basis by methods described in the Standard Operating Procedures Manual to determine their capacity to perform as required,
Reagents and solutions Frequency of testing along with controls
Anti-human serum Each day of use Blood grouping serums Each day of use Lectin Each day of use Antibody screening and reverse grouping cells
Each day of use
Hepatitis test reagents Each run Syphilis serology reagents Each run Enzymes Each day of use HIV I and II reagents Each run Normal saline (LISS and PBS) Each day of use Bovine Albumin Each day of use.
G. GOOD MANUFACTURING PRACTICES (GMPs) /STANDARD OPERATING PROCEDURES (SOPs):
Written Standard Operating Procedures shall be maintained and shall include all steps to be followed in the collection, processing, compatibility testing, storage and sale or distribution of blood and/or preparation of blood components for homologous transfusion, autologous transfusion and further manufacturing purposes. Such procedures shall be available to the personnel for use in concerned areas. The Standard Operating Procedures shall inter alia include:
1.(a) criteria used to determine donor suitability.
(b)
(c)
methods of performing donor qualifying tests and measurements including minimum and maximum values for a test or procedure, when a factor in determining acceptability;
solutions and methods used to prepare the site of phlebotomy so as to give maximum assurance of a sterile container of blood;
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(q) procedures of plasmapheresis, plateletphersis and leucapheresis if performed, including precautions to be taken to ensure re-infusion of donor’s own cells;
(r) procedures for preparing recovered (salvaged) plasma if performed, including details of separation, pooling, labelling, storage and distribution;
(s) All records pertinent to the lot or unit maintained pursuant to these regulations shall be reviewed before the release or distribution of a lot or unit of final product. The review or portions of the review may be performed at appropriate periods during or after blood collection, processing, testing and storage. A thorough investigation, including the conclusions and follow-up, if any unexplained discrepancy or the failure of a lot or unit to meet any of its specification shall be made and recorded.
2. A licensee may utilise current Standard Operating Procedures, such as the Manuals of the following organizations, so long as such specific procedures are consistent with, and at least as stringent as, the requirements contained in this Part, namely :-
(d) method of accurately relating the product (s) to the donor;
(e) blood collection procedure, including in-process precautions taken to measure accurately the quality of blood drawn from the donor;
(f) methods of component preparation including, any time restrictions for specific steps in processing;
(g) all tests and repeat test performed on blood and blood components during processing;
(h) pre-transfusion testing, wherever applicable, including precautions to be taken to identify accurately the recipient blood components during processing;
(i) procedures of managing adverse reactions in donor and recipient reactions:
(j) storage temperatures and methods of controlling storage temperatures for blood and its components and reagents;
(k) length of expiry dates, if any assigned for all final products;
(l) criteria for determining whether returned blood is suitable for re-issue;
(m) procedures used for relating a unit of blood or blood components from the donor to its final disposal;
(n) quality control procedures for supplies and reagents employed in blood collection, processing and re-transfusion testing;
(o) schedules and procedures for equipment maintenance and calibration;
(p) labelling procedures to safe guard its mix-ups, receipt, issue, rejected and in-hand;
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(i) Directorate General of Health Services Manual, (ii) Other Organisations’ or individual blood bank’s manuals, subject to the approval of
State Licensing Authority and Central Licence Approving Authority.
H. CRITERIA FOR BLOOD DONATION:
Conditions for donation of blood:
(1) General – No person shall donate blood and no blood bank shall draw blood from a person, more than once in three months. The donor shall be in good health, mentally alert and physically fit and shall not be inmates of jail, persons having multiple sex partners and drug- addicts. The donors shall fulfill the following requirements, namely: -
(a) the donor shall be in the age group of 18 to 60 years. (b) the donor shall not be less than 45 kilograms; ( c) temperature and pulse of the donor shall be normal; (d) the systolic and diastolic blood pressure and are within normal limits without
medication; (e) haemoglobin which shall not less than 12.5 grams; (f) the donor shall be free from acute respiratory diseases; (g) the donor shall be free from any skin diseases at the site of phlebotomy; (h) the donor shall be free from any disease transmissible by blood transfusion,
insofar as can be determined by history and examination indicated above; (i) the arms and forearms of the donor shall be free from skin punctures or scars
indicative of professional blood donors or addiction of self injected narcotics.
(2) Additional qualifications of donor – No person shall donate blood, and no blood bank shall draw blood from a donor, in the conditions mentioned in column (1) of the Table given below before the expiry of the period of deferment mentioned in the column (2) of the said Table.
Table: Deferment of blood donation
CONDITIONS (1)
PERIOD OF DEFERMENT (2)
(a) Abortions 6 months (b) History of Blood transfusion 6 months (c) Surgery 12 months (d) Typhoid 12 months after recovery (e) History of Malaria and duly
treated 3 months (endemic) 3 years (non endemic area)
(f) Tattoo 6 months (h) Breast feeding 12 months after delivery
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(i) Immunization (Cholera, Typhoid, Diphtheria, Tetanus, Plague, Gammaglobulin)
15 days
(j) Rabies vaccination 1 year after vaccination (k) History of Hepatitis in family or
close contact. 12 months
(l) Immunoglobulin 12 months
(5) No person shall donate blood and no blood bank shall draw blood from a person, suffering from any of the diseases mentioned below, namely:
a. Cancer b. Heart disease c. Abnormal bleeding tendencies d. Unexplained weight loss e. Diabetes -controlled on insulin
i. [(f) Hepatitis infection] (g) Chronic nephritis (h) Signs and symptoms, suggestive of AIDS (i ) Liver diseases (j) Tuberculosis (k) Polycythemia Vera. (l) Asthma (m) Epilepsy (n)Leprosy (o)Schizophrenia (p)Endocrine disorders
I. GENERAL EQUIPMENTS AND INSTRUMENTS: -
1. For blood collection room:
i) Donor beds, chairs and tables: These shall be suitably and comfortably cushioned and shall be of appropriate size.
ii) Bedside table iii) Sphygmomanometer and Stethoscope iv) Recovery beds for donors. v) Refrigerators, for storing separately tested and untested blood, maintaining
temperature between 2 to 6 degree centigrade with digital dial thermometer, recording thermograph and alarm device, with provision for continuous power supply.
vi) Weighing devices for donor and blood containers.
______________________________________________________________________ • Subs. by G.O.I Notification G.S.R. No.40 (E) Dt 29-01-2001.
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2. For haemoglobin determination:
3. For temperature and pulse determination.
4. For blood containers:
(i) Copper sulphate solution (specific gravity 1.053)
(ii) Sterile lancet and impregnated alcohol swabs.
(iii) Capillary tube (1.3 x 1.4 x 96mm) or Pasteur pipettes)
(iv) Rubber bulbs for capillary tubings.
(v) Sahli’s haemoglobinometer / Colorimetric method.
(i) Clinical thermometers
(ii) Watch (fitted with a second-hand) and a stop-watch.
(a) Only disposable PVC blood bags shall be used (closed system) as per specifications of IP/USP/BP.
(b) Anti-coagulants: The anti-coagulant solution shall be sterile, pyrogen-free and of the following composition that will ensure satisfactory safety and efficacy of the whole blood and/or for all the separated blood components.
Note 1. (i) In case of single/double/triple/quadruple blood collection bags used for blood component preparations,CPDA blood collection bags may be used.
(i) Citrate Phosphate Dextrose Adenine solution (CPDA) or Citrate Phosphate Dextrose Adenine – 1 (CPDA-1) – 14 ml solution shall be required for 100ml of blood.
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5. Emergency equipments/items:
6 Accessories: -
(ii) Acid Citrate Dextrose solution (A.C.D. with Formula -A) I.P. – 15 ml solution shall be required for 1—ml blood,
(iii) Additive solution such as SAGM, ADSOL, NUTRICEL may be used for storing and retaining Red Blood Corpuscles upto 42 days.
Note 2. The licensee shall ensure that the anti-coagulant solutions are of a licensed manufacturer and the blood bags in which the said solutions are contained have a certificate of analysis of the said manufacturer.
(i) Oxygen cylinder with masks, gauge and pressure regulator
(ii) 5 percent Glucose or Normal Saline
(iii) Disposable sterile syringes and needles of various sizes.
(iv) Disposable sterile I.V. infusion sets.
(v) Ampoules of Adrenaline, Noradrenaline, Mephentin, Betamethasone or Dexamethasone, Metoclorpropamide injections.
(vi) Aspirin.
(i) Such as blankets, emesis basins, haemostats, set clamps, sponge forceps, gauze, dressing jars, solution jars, waste cans.
(ii) Medium cotton balls, 1.25 cm adhesive tapes.
(iii) Denatured spirit, Tincture Iodine, green soap or liquid soap.
(iv) Paper napkins or towels. (v) Autoclave with temperature and pressure indicator.
(vi) Incinerator
(vii) Stand-by generator
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7. Laboratory equipment
viii) Hand-lens for observing tests conducted in tubes. (ix) Serological graduated pipettes of various sizes. (x) Pipettes (Pasteur) (xi) Glass slides (xii) Test tubes of various sizes / micrometer plates (U or V type) P xiii) Precipitating tubes 6mm x 50mm of different sizes and glass beakers of different
sizes. (xiv) Test tube racks of different specifications (xv) Interval timer electric or spring wound.
J SPECIAL REAGENTS : (1) Standard blood grouping sera Anti A, Anti B and Anti C with known controls.
Rh typing sera shall be in double quality and each of different brand or if from the same supplier each supply shall be of different lot numbers,
(2) Reagents for serological tests for syphilis and positive sera for controls. (3) Anti Human Globulin Serum (Coomb’s serum) (4) Bovine Albumin 22 percent Enzyme reagents for incomplete antibodies. (5) ELISA or RPHA test kits for Hepatitis and HIV I & II (6) Detergent and other agents for cleaning laboratory glass wares.
(i) Refrigerators, for storing diagnostic kits and reagents, maintaining a temperature between 4 to 6 degree centigrade (plus/minus 2 degrees centigrade) with digital dial thermometer having provision for continuous power supply.
(ii) Compound Microscope with low and high power objectives (iii) Centrifuge Table Model (iv) Water bath: having range between 37 degree centigrade to 56 degree centigrade. (v) Rh viewing box in case of slide technique (vi) Incubator with thermostatic control (vii) Mechanical shakers for serological tests for Syphilis.
(xviii) Wash bottles. (xix) Filter papers (xx) Dielectric tube sealer (xxii) Plain and EDTA vials (xxii) Chemical balance (wherever necessary) (xxiii) ELISA reader with printer, washer and micropipettes.
(xvi) Equipment and materials for cleaning glass wares adequately. (xvii) Insulated containers for transporting blood, between 2 degree centigrade to 10
degree centigrade temperatures, to wards and hospitals.
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K. TESTING OF WHOLE BLOOD :
NOTE (a) Blood samples of donors in pilot tube and the blood samples of the recipient shall be preserved for 7 days after issue.
(b) The blood intended for transfusion shall not be frozen at any stage.
(c) Blood containers shall not come directly in contact with ice at any stage.
L. RECORDS :
The records which the licensee is required to maintain shall include interalia the following particulars, namely: -
_________________________________________________________________ * Subs. by G.O.I Notification G.S.R. No.40(E) dt 29-01-2001.w.e.f.01.06.2001
(1) It shall be responsibility of the licensee to ensure that the whole blood collected, processed and supplied conforms to the standards laid down in the Indian Pharmacopoeia and other tests published, if any, by the Government.
(2) Freedom from HIV antibodies (AIDS) Tests – Every licensee shall get samples of every blood unit tested, before use, for freedom from HIV 1 and HIV II antibodies either from laboratories specified for the purpose by the Central Government or in his own laboratory. The results of such testing shall be recorded on the label of the container.
(3) Each blood unit shall also be tested for freedom from *[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] VDRL and malarial parasite and results of such testing shall be recorded on the label of the container.
(1) Blood donor record : It shall indicate serial number, date of bleeding, name, address and signature of donor with other particulars of age, weight, hemoglobin, blood grouping, blood pressure, med ical examination, bag number and patient’s detail for whom donated in case of replacement donation, category of donation (voluntary / replacement) and deferral records and signature of Medical Officer In charge.
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( (5) Records of A.C.D./C.P.D/CPD-A/SAGM bags giving details of manufacturer, batch number, date of supply and results of testing .
(6) Register for diagnostic kits and reagents used: name of the kits/reagents, details of batch number, date of expiry and date of use.
(7) Blood bank must issue the cross matching report of the blood to the patient together with the blood unit.
(8) Transfusion adverse reaction records.
(9) Records of purchase, use and stock in hand of disposable needles, syringes, blood bags, shall be maintained.
NOTE : The above records shall be kept by the licensee for a period of five years.
M LABELS :
The labels on every bag containing blood and/or component shall contain the following particulars, namely;
(1) The proper name of the product in a prominent place and in bold letters on the bag.
(2) Name and address of the blood bank
(3) Licence number
________________________________________________________________________ **Subs. by G.O.I Notification G.S.R. No.40(E) dt 29-01-2001.w.e.f.01.06.2001.
(2) Master records for blood and its components: It shall indicate bag serial number, date of collection, date of expiry, quantity in ml. ABO/Rh Group, results for testing of HIV I and HIV II antibodies, Malaria, V.D.R.L. **[( Hepatitis B surface antigen and Hepatitis C Virus antibody)] and irregular antibodies (if any), name and address of the donor with particulars, utilization issue number, components prepared or discarded and signature of the Medical Officer in charge.
(3) Issue register: It shall indicate serial number, date and time of issue, bag serial number, ABO/Rh Group, total quantity in ml, name and address of the recipient, group of recipient, unit/institution, details of cross-matching report, indication for transfusion.
(4) Records of components supplied: quantity supplied, compatibility report, details of recipient and signature of issuing person.
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(4) Serial number
(5) The date on which the blood is drawn and the date of expiry as prescribed under Schedule P to these rules.
(6) A colored label shall be put on every bag containing blood. The following color scheme for the said labels shall be used for different groups of blood:
Blood Group Color of the label
O Blue A Yellow B Pink AB White
(7) The results of the tests for **[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] syphilis, freedom from HIV I and HIV II antibodies and malarial parasite.
(8) The Rh. Group
(9) Total volume of blood, the preparation of blood, nature and percentage of anti- coagulant.
(10) Keep continuously temperature at 2 degree centigrade to 6 degree centigrade for whole human blood and/or components as contained under III of Part XII B.
(11) Disposable transfusion sets with filter shall be used in administration equipment.
(12) Appropriate compatible cross-matched blood without atypical antibody in recipient shall be used.
(13) The contents of the bag shall not be used if there is any visible evidence of deterioration like haemolysis, clotting or discoloration.
(14) The label shall indicate the appropriate donor classification like “Voluntary Donor” or “Replacement Donor” in no less prominence than the proper name.
________________________________________________________________________ **Subs. by G.O.I Notification G.S.R. No.40(E) dt 29-01-2001.w.e.f.01.06.2001
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NOTES :
1. In the case of blood components, particulars of the blood from which such components have been prepared shall be given against item numbers (5), (7), (8), (9) and (14).
2. The blood and/or its components shall be distributed on the prescription of a Registered Medical Practitioner.
I I. BLOOD DONATION CAMPS.
A blood donation camp may be organized by –
(a) a licensed designated Regional Blood Transfusion Centre ; or (b) a licensed Government blood bank; or **[(c) the Indian Red Cross society; or (d) a licensed blood bank run by registered voluntary or charitable organizations
recognized by State or Union Territory Blood Transfusion Council)]
NOTES:
(i)“ Designated Regional Blood Transfusion Centre” shall be a center approved and designated by a Blood Transfusion Council constituted by a State Government to collect, process and distribute blood and its components to cater to the needs of the region and that center has also been licensed and approved by the Licensing Authority and Central Licence Approving Authority for the purpose.
(ii) The designated Regional Blood Transfusion Centre, Government blood bank and Indian Red Cross Society shall intimate within a period of seven days, the venue where the blood camp was held and details of group wise blood units collected in the said camp to the Licensing Authority and Central Licence Approving Authority.
For holding a blood donation camp, the following requirements shall be fulfilled/complied with, namely: -
(A) Premises, personnel etc.
(a) Premises under the blood donation camp shall have sufficient area and the location shall be hygienic so as to allow proper operation, maintenance and cleaning.
_______________________________________________________ **Subs. by G.O.I Notification G.S.R. No.218(E) dt 28-03-2001
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(b) All information regarding the personnel working, equipment used and facilities available at such a Camp shall be well documented and made available for inspection, if required, and ensuring -
(i) Continuous and uninterrupted electrical supply for equipment used in the Camp;
(ii) Adequate lighting for all the required activ ities; (iii) Hand-washing facilities for staff; (iv) Reliable communication system to the central office of the
Controller/organizer of the Camp; (v) Furniture and equipment arranged within the available space; (vi) Refreshment facilities for donors and staff; (vii) Facilities for medical examination of the donors; (viii) Proper disposal of waste.
(B) Personnel for Out-door Blood Donation Camp:
To collect blood from 50 to 70 donors in about 3 hours or from 100 to 200 donors in 5 hours, the following requirements shall be fulfilled / complied with:
(i) One Medical Officer and two nurses or phlebotomists for managing 6-8 donor tables.
(ii) two medico social workers (iii) three blood bank technicians (iv) two attendants (v) vehicle having a capacity to seat 8-10 persons, with provision for carriage
of donation goods including facilities to conduct a blood donation camp.
(C) Equipments :
1. BP apparatus 2. Stethoscope 3. Blood bags (single, double, triple, quadruple) 4. Donor questionnaire 5. Weighing device for donors 6. Weighing device for blood bags 7. Artery forceps, scissors 8. Stripper for blood tubing 9. Bed sheets, blankets/mattress 10. Lancets, swab stick/tooth picks 11. Glass slides 12. Portable Hb meter/copper sulphate
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13. Test tube (big) and 12x100mm (small) 14. Test tube stand 15. Anti-A, Anti-B and Anti-AB, Antisera and Anti-D 16. Test tube sealer film 17. Medicated adhesive tape 18. Plastic waste basket 19. Donor cards and refreshment for donors 20 Emergency medical kit 21 Insulated blood bag containers with provisions for storing between 2
degree centigrade to 10 degree centigrade. 22. Dielectric sealer or portable tube sealer 23. Needle destroyer (wherever necessary)
III. PROCESSING OF BLOOD COMPONENTS FROM WHOLE BLOOD BY A BLOOD BANK
The Blood components shall be prepared by blood banks as a part of the Blood Bank services. The conditions for grant or renewal of licence to prepare blood components shall be as follows: -
A ACCOMMODATION
(1) Rooms with adequate area and other specification, for preparing blood components depending on quantum of workload shall be specified in item B under the heading “1. BLOOD BANKS/BLOOD COMPONENTS’ of this Part.
(2) Preparation of Blood components shall be carried out only under closed system using single double, triple or quadruple plastic bags except for peroration of Red Blood Cells Concentrates, where single bags may be used with transfer bags.
B EQUIPMENT :
(i) Air Conditioner; (ii) Laminar air flow bench; (iii) Suitable refrigerated centrifuge; (iv) Plasma expresser; (v) Clipper and clips and or dielectric sealer; (vi) Weighing device; (vii) Dry rubber balancing material; (viii) Artery forceps, scissors; (ix) Refrigerator maintaining a temperature between 2 degree centigrade to 6
degree centigrade, a digital dial thermometer with recording thermograph and alarm device, with provision for continuous power supply;
(x) Platelet agitator with incubator (wherever necessary) (xi) Deep freezers maintaining a temperature between minus 30 degree
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centigrade to minus 40 degree centigrade and minus 75 degree centigrade to minus 80 degree centigrade;
(xii) Refrigerated Water bath for Plasma Thawing; (xiii) Insulated blood bag containers with provisions for storing at appropriate
temperature for transport purposes;
C. PERSONNEL:
The whole time competent technical staff meant for processing of Blood Components (that is Medical Officer, Technical Supervisor, Blood Bank Technicians and Registered Nurse) shall be as specified in item C, under the heading “ 1. BLOOD BANKS/BLOOD COMPONENTS” of this Part.
D. TESTING FACILITIES:
General: Facilities for A, B, AB and O groups and Rh(D) grouping. [*(Hepatitis B surface antigen and Hepatitis C Virus antibody)] VDRL, HIV and HIV II antibodies and malarial parasites shall be mandatory for every blood unit before it is used for the preparation of blood components. The results of such testing shall be indicated on the label.
E. CATEGORIES OF BLOOD COMPONENTS:
(1) CONCENTRATED HUMAN RED BLOOD CORPUSCLES:
The product shall be known as “Packed Red Blood Cells” that is Packed Red Blood Cells remaining after separating plasma from human blood.
General Requirements:
(a) Storage: Immediately after processing, the Packed Red Blood Cells shall be kept at a temperature maintained between 2 degree centigrade to 6 degree centigrade.
(b) Inspection: The component shall be inspected immediately after separation of the plasma, during storage and again at the time of issue. The product shall not be issued if there is any abnormality in color or physical appearance or any indication of microbial contamination.
(c) Suitability of Donor: The source of blood for Packed Red Blood Cells shall be obtained from a donor who meets the criteria for Blood Donation as specified in item H under the heading “I. BLOOD BANKS/BLOOD COMPONENTS” of this Part.
__________________________________________________________________ *Subs. by G.O.I Notification G.S.R. No.40(E) dt 29-01-2001 w.e.f. 01.06.2001
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(d) Testing of Whole Blood: Blood from which Packed Red Blood Cells are prepared shall be tested as specified in item K relating to Testing Of Whole Blood under the heading “I. BLOOD BANKS/BLOOD COMPONENTS” of this Part.
(e) Pilot samples: Pilot samples collected in integral tubing or in separate pilot tubes shall meet the following specifications:
(i) One or more pilot samples of either the original blood or the Packed Red Blood Cells being processed shall be preserved with each unit of Packed Red Blood Cells, which is issued.
(ii) Before they are filled, all pilot sample tubes shall be marked or identified so as to relate them to the donor of that unit or Packed Red Blood Cells.
(iii) Before the final container is filled or at the time the final product is prepared, the pilot samples tubes accompanying a unit of Packed Red Blood Cells, shall be attached in a tamper-proof manner that shall conspicuously identify removal and re-attachment.
(iv) All pilot sample tubes, accompanying a unit of packed red blood cells, shall be filled immediately after the blood is collected or at the time the final product is prepared, in each case, by the person who performs the collection of preparation.
F PROCESSING:
(i) Separation: Packed Red Blood Cells shall be separated from the whole blood, --
(a) if the whole blood is stored in ACD solution within 21 days, and
(b) if the whole blood is stored in CPDA-1 solution, within 35 days, from the date of collection. Packed Red Blood Cells may be prepared either by centrifugation done in a manner that shall not tend to increase the temperature of the blood or by normal undisturbed sedimentation method. A portion of the plasma, sufficient to ensure optimal cell preservation, shall be left with the packed Red Blood Cells.
(ii) Packed Red Blood Cells Frozen: Cryophylactic substance may be added to the Packed Red Blood Cells for extended manufacturer’s storage not warmer than minus 65 degree centigrade provided the manufacturer submits data to the satisfaction of the Licensing Authority and Central Licence Approving Authority, as adequately demonstrating through in- vivo cells survival and other appropriate tests that the addition of the substance, the material used and the processing methods results in a final
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product meets the req uired standards of safety, purity and potency for Packed Red Blood Cells, and that the frozen product shall maintain those properties for the specified expiry period.
(iii) Testing: Packed Red Blood Cells shall conform to the standards as laid down in the Indian Pharmacopoeia.
(2) PLATELETS CONCENTRATES:
The product shall be known as “Platelets Concentrates” that is platelets collected from one unit of blood and re-suspended in an appropriate volume of original plasma.
General Requirements:
(i) Source: The source material for platelets shall be platelet rich plasma or buffy coat which may be obtained from the whole blood or by plateletpheresis.
(ii) Processing :
(a) Separation of buffy-coat or platelet-rich plasma and platelets and re- suspension of the platelets shall be in a closed system by centrifugal method with appropriate speed, force and time.
(b) Immediately after collection, the whole blood or plasma shall be held in storage between 20 degree centigrade to 24 degree centigrade. When it is to be transported from the venue of blood collected to the processing laboratory, during such transport action, the temperature as close as possible to a range between 20 degree centigrade to 24 degree centigrade shall be ensured. The platelet concentrates shall be separated within 6 hours after the time of collection of the unit of whole blood or plasma.
(c) The time and speed of centrifugation shall be demonstrated to produce an unclamped product, without visible haemolysis, that yields a count of not less than 3.5 x 10 10 (3.5 x 10 raised to the power of 10) and 4.5 x 10 10 (4.5 x 10 raised to the power ten) i.e. platelets per unit from a unit of 350ml and 450ml blood respectively. One percent of total platelets prepared shall be tested of which 75 per cent of the units shall conform to the above said platelet count.
(d) The volume of original plasma used for re-suspension of the platelets shall be determined by the maintenance of the pH of not less than 6 during the storage period. The pH shall be measured on a sample of platelets which has been stored for the permissible
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maximum expiry period at 20 degree centigrade to 24 degree centigrade.
(e) Final containers used for platelets shall be colorless and transparent to permit visual inspection of the contents. The caps selected shall maintain a hermetic seal to prevent contamination of the contents. The container material shall not interact with the contents, under the normal conditions of the storage and use, in such a manner as to have an adverse effect upon the safety, purity, potency, or efficacy of the product. At the time filling, the final container shall be marked or identified by number so as to relate it to the donor.
(iii) Storage: Immediately after re-suspension, platelets shall be placed in storage not exceeding for a period of 5 days, between 20 degree centigrade to 24 degree centigrade, with continuous gentle agitation of the platelet concentrates maintained throughout such storage
(iv) Testing: The units prepared from different donors shall be tested at the end of the storage period for –
(a) Platelet count; (b) pH of not less than 6 measured at the storage temperature of the
unit; (c) measurement of actual plasma volume; (d) one percent of total platelets prepared shall be tested for
sterility; (e) the tests of functional viability of the platelets shall be done by
swirling movement before issue. (f) if the results of the testing indicate that the product does not
meet the specified requirements, immediate corrective action shall be taken and records maintained;
(v) Compatibility Test: Compatible transfusion for the purpose of variable number of Red Blood Cells, A, B, AB and O grouping shall be done if the platelets concentrate is contaminated with red blood cells.
(3) GRANULOCYTE CONCENTRATES:
(i) Storage: It shall be kept between 20 degree centigrade to 24 degree centigrade for a maximum period of 24 hours;
(ii) Unit of granulocytes shall not less than 1 x 10 10 (i.e. 1 x 10 raised to the power of 10) when prepared on cell separator.
(iii) Group specific tests/HLA test wherever required shall be carried out.
(4) FRESH FROZEN PLASMA:
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Plasma frozen within 6 hours after blood collection and stored at a temperature not warmer than minus 30 degree centigrade, shall be preserved for a period of not more than one year.
(5) CRYOPRECIPITATE:
Concentrate of anti-hemophiliac factor shall be prepared by thawing of the fresh plasma frozen stored at minus 30 degree centigrade.
(a) Storage: Cryoprecipitate shall be preserved at a temperature not higher than minus 30 degree centigrade and may be preserved for a period of not more than one year from the date of collection.
(b) Activity: Anti-hemophiliac factor activity in the final product shall be not less than 80 units per bag. One percent of the total cryoprecipitate prepared shall be tested of which seventy five percent of the unit shall conform to the said specification.
(6) PLASMAPHERESIS, PLATELETPHERESIS, LEUCAPHERESIS, USING A CELL SEPARATOR.
An area of 10 square meters shall be provided for apheresis in the blood bank.
The blood banks specifically permitted to undertake the said apheresis on the donor shall observe the criteria as specified in item H relating to Criteria for blood donation “I Blood Banks/Blood Components” of this Part. The written consent of the donor shall be taken and the donor must be explained, the hazards of apheresis. The Medical Officer shall certify that the donor is fit for apheresis and it shall be carried out by a trained person under supervision of the Medical Officer.
(A) PLASMAPHERESIS,PLATELETPHERESISANDLEUCAPHERESIS: The donors subjected to plasmapheresis, plateletpheresis and leucopheresis shall, in addition to the criteria specified in item H relating to the CRITERIA FOR BLOD DONATION, under the heading “I. BLOOD BANKS/BLOOD COMPONENTS” of this Part being observed, be also subjected to protein estimation on post-pheresis/first sitting whose results shall be taken as reference for subsequent pheresis/sitting. It shall also be necessary that the total plasma obtained from such donor and periodicity of Plasmapheresis shall be according to the standards described under validated Standard Operating Procedures.
NOTE :
(i) At least 48 hours must elapse between successive apheresis and not more than twice in a week.
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(ii) Extracoporeal blood volume shall not exceed 15% of donor’s estimated blood volume.
(iii) Platelet pheresis shall not be carried out on donors who have taken medication containing Asprin within 3 days prior to donation.
(iv) If during plateletpheresis or leucapheresis, RBCs cannot be re- transfused then at least 12 weeks shall elapse before a second cytapheresis procedure is conducted.
(B) MONITORING FOR APHERESIS:
Before starting apheresis procedure, hemoglobin or haematocrit shall be done. Platelet count, WBC counts, differential count may be carried out. In repeated plasmapheresis, the serum protein shall be 6 gm./ml.
(C) COLLECTION OF PLASMA: The quantity of plasma separated from the blood of donor shall not exceed 500 ml. per sitting and once in a fortnight or shall not exceed 1000 ml per month.
PART XII C
I. REQUIREMENTS FOR MANUFACTURE OF BLOOD PRODUCTS.
The blood products shall be manufactured in a separate premises other than that meant for blood bank. The requirements that are essential for grant or renewal of licence to manufacture blood products such as Albumin, Plasma Protein Fraction, Immunoglobins and Coagulation Factor Concentrates, shall be as follows, namely: -
A. GENERAL REQUIREMENTS: 1. Location and surroundings, buildings and water supply:
The requirements as regards location and surrounding, buildings and water supply as contained in paragraphs 1.1.1, 1.1.2, 1.1.3 of Part 1 of Schedule M shall apply mutatis mutandis to the manufacture of blood products.
2. Disposal of waste and infectious materials: (i) The requirements as regards dis posal of waste and infectious materials as
contained in paragraph 1.1.4 of Part 1 of Schedule M shall apply mutatis mutandis to the manufacture of blood products.
(ii) Proper facility shall also be provided for potentially infectious materials, particularly HIV I & HIV II *[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] through autoclaving, incineration or any other suitable validated methods.
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3. Health, clothing and sanitation personnel:
(i) The requirement as contained in paragraph 3 of Part 1 of Schedule M shall be complied with.
(ii) The personnel working in the manufacturing areas shall be vaccinated against Hepatitis B virus and other infectious transmitting diseases
4. Requirements for manufacturing area for Blood Products:
(i) For the manufacture of blood products, separate enclosed areas specifically designated for the purpose shall be provided. These areas be provided with air locks for entry and shall be essentially dust free and ventilated with an air supply. Air supply for manufacturing area shall be filtered through bacteria retaining filters (HEPA Filters) shall be at a pressure higher than in the adjacent areas.
The filters shall be checked for performance on installation and periodically thereafter all records thereof shall be maintained.
(ii) Interior surfaces (walls, floors and ceilings) shall be smooth and free from cracks; they shall not shed matter and shall permit easy cleaning and disinfection. Drains shall be excluded from aseptic areas.
Routine microbial counts of the manufacturing area shall be carried out during manufacturing operations. The results of such counts shall be checked against well documented in-house standards and records maintained.
Access to the manufacturing areas shall be restricted to a minimum number of authorized personnel. Special procedures for entering and leaving the manufacturing areas shall be prominently displayed.
(iii) Sinks shall be excluded from aseptic areas. Any sink installed in other clean areas shall be of suitable material such as stainless steel, without an overflow, and be supplied with water of potable quality. Adequate precautions shall be taken to avoid contamination of the drainage system with dangerous effluents and airborne dissemination of pathogenic micro-organisms.
___________________________________________________________________ *Subs. by G.O.I Notification G.S.R. No.40(E) dt 29-01-2001 w.e.f. 01.06.2001.
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(iv) Lighting, air-conditioning, ventilation shall be designed to maintain a satisfactory temperature and relative humid ity to minimize contamination and to take account of the comfort of personnel working with protective clothing.
(v) Premises used for the manufacture of blood products shall be suitably designed and constructed to facilitate good sanitation.
(vi) Premises shall be carefully maintained and it shall be ensured that repair and maintenance operations do not present any hazard to the quality of products. Premises shall be cleaned and, where applicable, disinfected according to detailed written validated procedures.
(vii) Adequate facilities and equipments shall be used for the manufacture of blood products derived from blood plasma.
(viii) All containers of blood products, regardless of the stage of manufacture, shall be identified by securely attached labels. Cross contamination shall be prevented by adoption of the following measures, namely -
(a) processing and filling shall be in segregated areas;
(b) manufacture of different products at the same time shall be avoided;
(c) simultaneous filling of the different products shall be avoided;
(d) ensure transfer, containers/materials by means of airlocks, air extraction, clothing change and careful washing and decontamination of equipment;
(e) protecting containers/materials against the risk of contamination caused by re-circulation of untreated air or by accidental re-entry of extracted air;
(f) using container that are sterilized or are of documented low “bioburden”,
(ix) Positive pressure area shall be dedicated to the processing area concerned;
(x) Air-handling units shall be dedicated to the processing area concerned;
(xi) Pipe work, valves and vent filters shall be properly designed to facilitate cleaning and sterilization. Valves on fractionation / reacting vessels shall be completely steam sterilisable. Air vent filters shall be validated for their designated use.
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5. Ancillary Areas :
(i) Rest and refreshment rooms shall be separated from other areas.
(ii) Facilities for changing and storing clothes and for washing and toilet purposes shall be easily accessible and appropriate for the number of users. Toilets shall not be connected directly with production or storage areas.
(iii) Maintenance workshops shall be separated from production areas. Wherever parts and tools are stored in the production area, they shall be kept in rooms or lockers reserved for that use.
(iv)Animal houses shall be well isolated from other areas with separate entrance.
COLLECTION AND STORAGE OF PLASMA FOR FRACTIONATION
(A) COLLECTION:
(1) Plasma shall be collected from the licensed Blood Banks through a cold chain process and stored in frozen condition not warmer than minus twenty degree centigrade.
(2) Individual plasma shall remain in quarantine till it is tested for *[( Hepatitis B and Hepatitis C Virus antibody)], HIV I and HIV II.
(3) A sample from pooled – lot plasma of about 10-12 units of different donors shall be tested for [(Hepatitis B and Heptitis C Virus antibody)] HIV I and HIV II and if the same sample found negative, only then it shall be taken up for fractionation.
(B) STORAGE AREA :
(1) Storage areas shall be of sufficient space and capacity to allow orderly storage of the various categories of materials, intermediates, bulk and finished products, products in quarantine, released, rejected, returned, or recalled products.
(2) Storage areas shall be designed or adopted to ensure good storage containers. In particular, they shall be clean, dry and maintained within temperature required for such storage and where special storage conditions are required (e.g. temperature, humidity), these shall be provided, checked and monitored.
________________________________________________________________________ *Subs. by G.O.I Notification G.S.R. No.40(E) dt 29-01-2001 w.e.f. 01.06.2001
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(3) Receiving and dispatch bays shall protect materials and products from the weather and shall be designed and equipped to allow containers of incoming materials to be cleaned, if necessary, before storage.
(4) Where quarantine status is ensured by storage in separate areas, these areas shall be clearly marked and their access restricted only to authorized personnel.
(5) There shall be separate sampling area for raw materials. If sampling is performed in the storage area, it shall be conducted in such a way so as to prevent contamination or cross-contamination.
(6) Segregation shall be provided for the storage of rejected, recalled, or returned materials or products.
(7) Adequate facility shall be provided for supply of ancillary material, such as ethanol, water, salts and polyethylene glycol. Separate facilities shall be provided for the recovery of organic solvents used in fractionation.
C. PERSONNEL :
1. Manufacture : The manufacture of blood products shall be conducted under the active direction and personal supervision of competent technical staff, consisting of at least one person who shall be a whole time employee, with one year practical experience in the manufacture of blood products / plasma fractionation and possesses –-
(a) Post-graduate degree in Medicine – M.D. (Mic robiology / Pathology / Bacteriology / Immunology / Biochemistry) ; or
(b) Post graduate degree in Science (Microbilogy); or
(c) Post-graduate degree in Pharmacy (Microbiology), from a recognized University or Institution.
2. Testing : The head of the testing unit shall be independent of the manufacturing unit and testing shall be conducted under the active direction and personal supervision of competent technical staff consisting at least one person who shall be a whole time employee. The Head of the testing unit shall have eighteen months practical experience in the testing of drugs, especially the blood products and possesses –
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(a) Post-graduate degree in Pharmacy or Science – (Chemistry / Microbiology / Bio-chemistry); or
(b) Post-graduate degree in Medicine – M.D (Microbiology / Pathology / Biochemistry), from a recognized University or Institution.
D. PRODUCTION CONTROL :
(1) The production area and the viral inactivation room shall be centrally air- conditioned and fitted with HEPA filters having Grade C (Class 10,000) environment as given in the Table below.
(2) The filling and sealing shall be carried out under aseptic conditions in centrally air-conditioned areas fitted with HEPA Filters Grade A or as the case may be grade B (Class 100) environment given in the said Table.
TABLE AIR CLASSIFICATION SYSTEM FOR MANUFACTURE OF STERILE
PRODUCTS.
Maximum number of particles permitted per m3
MAXIMUM NUMBER OF PARTICLES PERMITTED PER m3
MAXIMUM NUMBER OF VIABLE MICROORGANISM PERMITTED PER m3
GRADE 0.5 – 5 micron Less than 5 micron
A (Class 100) (Laminar - Airflow workstation)
3500 None Less than 1
B (Class 100) 3500 None Less than 5
C (Class 10000) 3,50,000 2000 Less than 100
(3) The physical and chemical operations used for the manufacture of plasma fractionation shall maintain high yield of safe and effective protein.
(4) The fractionation procedure used shall give a good yield of products meeting the in-house quality requirements as approved by the Licensing Authority and Central Licence Approving Authority reducing the risk of microbiological contamination and protein denaturation to the minimum.
(5) The procedure adopted shall not affect the antibody activity and biological half-life or biological characteristics of the products.
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E. VIRAL INACTIVATION PROCESS :
The procedure used by the licensee to inactivate the pathogenic organisms such as enveloped and non-enveloped virus, especially infectivity from HIV I & HIV II, **[(Hepatitis B surface antigens and Hepatitis C Virus antibody)], the viral inactivation and validation methods adopted by the licensee, shall be submitted for approval to the Licensing Authority and Central Licence Approving Authority.
NOTES:
(1) No preservative (except stabilizer to prevent – protein denaturatin such as glycine, sodium chloride or sodium caprylate) shall be added to Albumin, Plasma Protein Fraction, Intravenous Immunoglobulins or Coagulation Factor Concentrates without the prior approval of Licensing Authority and Central Licence Approving Authority.
(2) The licensee shall ensure that the said stabilizers do not have deleterious effect on the final product in the quality present so as not to cause any untoward or adverse reaction in human beings.
F. QUALITY CONTROL:
Separate facilities shall be provided for Quality Control such a Hematological, Bio- chemical, Physico-chemical, Microbiological, Pyrogens, Instrumental and Safety testing. The Quality Control Department shall have inter alia the following principal duties, namely :-
(1) To prepare detailed instructions for carrying our test and analysis.
(2) To approve or reject raw material, components, containers, closures, in - process materials, packaging material, labeling and finished products.
(3) To release or reject batch of finished products which are ready for distribution.
(4) To evaluate the adequacy of the conditions under which raw materials, semi- finished products and finished products are stored.
(5) To evaluate the quality and stability of finished products and when necessary of raw materials and semi-finished products.
* *Subs. by G.O.I Notification G.S.R. No.40(E) dt 29-01-2001 w.e.f. 01.06.2001
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6) To review production records to ensure that no errors have occurred or if errors have occurred that they have been fully investigated.
(7) To approve or reject all procedures, or specifications impacting on the identity, strength, quality and purity of the product.
(8) To establish shelf-life and storage requirements on the basis of stability tests related to storage conditions.
(9) To establish and when necessary revise, control procedures and specifications.
(10)
(11)
To review complaints, recalls, returned or salvaged products and investigations conducted there under for each product.
To review Master Formula Records/Cards periodically.
G. TESTING OF BLOOD PRODUCTS:
The products – manufactured shall conform to the standards specified in the Indian Pharmacopoeia and where standard of any product is not specified in the Pharmacopoeia, the standard for such product shall conform to the standard specified in the United States Pharmacopoeia or the British Pharmacopoeia. The final products shall be tested for freedom from HIV I and HIV II antibodies *[(Hepatitis B surface antigen and Hepatitis C Virus antibody)]
H. STORAGE OF FINISHED PRODUCT ;
(i) The final products shall be stored between two degree centigrade to eight degree centigrade, unless otherwise specified by the Central Licence Approving Authority.
(ii)The shelf-life assigned to the products by the licensee shall be submitted for approval to the Licensing Authority and Central Licence Approving Authority.
I. LABELLING : The products manufactured shall be labeled as specified in the Indian Pharmacopoeia, the British Pharmacopoeia or the United Stated Pharmacopoeia which shall be in addition to any other requirement stated under Part IX or Part X of these rules. The labels shall indicate the results of test for *[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] freedom from HIV I and HIV II antibodies.
______________________________________________________ *Subs. by G.O.I Notification G.S.R. No.40(E) dt 29-01-2001 w.e.f. 01.06.2001
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J. RECORDS: The licensee shall maintain records as per Schedule U and also comply with Batch manufacturing records as specified in Paragraph 9 part 1 of Schedule M and any other requirement as may be directed by Licensing Authority and Central Licence Approving Authority.
K. MASTER FORMULA RECORDS:
The licensee shall maintain Master Formula Records relating to all manufacturing and quality control procedures for each product, which shall be prepared and endorsed by the competent Technical Staff, i.e. Head of the manufacturing unit. The Master Formula Records shall contain –
(i) the patent or proprietary name of the product along with the generic name, if any, strength and the dosage form;
(ii) a description or identification of the final containers, packaging materials, labels and closures to be used;
(iii) the identity, quantity and quality of each raw material to be used irrespective of whether or not it appears in the finished product. The permissible overage that may be included in a formulated batch shall be indicated;
(iv) a description of all vessels and equipments and the sizes used in the process; (v) manufacturing and control instructions along with parameters for critical steps
such as mixing, drying, blending, sieving and sterilizing the product; (vi) the theoretical yield to be expected from the formulation at different stages of
manufacture and permissible yield limits; (vii) detailed instructions on precautions to be taken in the manufacture and storage of
drugs and of semi finished products; and (viii) the requirements in-process quality control tests and analysis to be carried out
during each stage of manufacture including the designation of persons or departments responsible for the execution of such tests and analysis.
II. REQUIREMENTS FOR MANUFACTURE OF BLOOD PRODUCTS FROM BULK FINISHED PRODUCTS.
Where the blood products, such as Albumin, Plasma Protein Fraction, Immunoglobulins and Coagulation Factor Concentrates are manufactured through the manufacturing activities of filling and sealing the blood products from bulk powder or solution or both, the requirements as they apply to the manufacture of blood products from whole blood shall apply mutates mutandis to such manufacture of blood products, unless other requirements have been approved by the Central Licence Approving Authority.
_____________________________________________________________________ *Subs. by G.O.I Notification G.S.R. No.40(E) dt 29-01-2001 w.e.f. 01.06.2001
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1PART XIII – GENERAL
1. For the purposes of this Schedule, any test or method of testing described in the Indian Pharmacopoeia shall be deemed to be a method approved by the Licensing Authority.
2. The Licensing Authority shall publish in the Official Gazette from time to time particulars of any test or method of testing approved by him.
2SCHEDULE F(I)
PART 1- VACCINES
(A) PROVISIONS APPLICABLE TO THE PRODUCION OF BACTERIAL VACCINES.
1. Definition- (1) This part of the Schedule applies to bacterial vaccines made from any micro-organism pathogenic to man or other animal and to vaccines made from other micro- organisms which have any antigenic value.
(2). For the purposes of this part of the Schedule, a bacterial vaccine means a sterile suspension of a killed culture of the micro-organism from which the vaccine derives its name or a sterile extract or derivative of a micro-organism, or a pure suspension of living micro- organisms which have been previously made avirulent.
2. Staff of Establishment- A competent expert in bacteriology with sufficient experience in the manufacture and standardisation of biological products shall be in charge of the establishment responsible for the production of bacterial vaccine and he shall be assisted by a staff adequate for carrying out the tests required during the preparation and standardisation of the vaccines.
3. Proper Name- The proper name of any vaccine shall be the name of the micro- organism from which it is made followed by the word “Vaccine”
1Renumbered under Government of India Notification No. F-18-1/46, dated 18-6-48 2Added under Government of India, Ministry of Health F.P., W.H and U.D. Notification No. F.1-6/62-D, dated 2-7-1969
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unless this Schedule otherwise provides or if there is no other special provision in the Schedule, some other name as approved by the Licensing Authority. Provided that in the case of the undermentioned preparations the proper name of the vaccine may be as follows:-
1. Anthrax Spore Vaccine (Living). 2. Blackquarter Vaccine. 3. Enterotoxaemia Vaccine. 4. Fowl Cholera Vaccine. 5. Haemorrhagic Septicaemia Adjuvant Vaccine. 6. Haemorrhagic Septicaemia Vaccine (Broth). *[7. Multi Component Clostridial Vaccine. 8. Hemorrhagic Septicaemia Vaccine – Alum Treated.]
4. Records.- Cultures used in the preparation of vaccine before being manipulated into a vaccine, should be thoroughly tested for identity by the generally accepted tests applicable to the particular micro -organisms.
The permanent records which the licensee is required to keep shall include amongst others, a record of the origin, properties and characteristics of the cultures.
5. Combined Vaccines- Vaccines may be issued either singly or combined in any proportion in the same container. In the case of combination of vaccines, a name for the combined vaccine may be submitted by the licensee to the Licensing Authority, and if approved, may be used as the proper name of the vaccine.
6. Preparation- Bacterial vaccines, simple or polyvalent, are prepared from selected cultures after careful examination for their identity, specificity, purity and antigencity. They may be prepared in the following manner:-
(a). Formal Cultures or Bacterins- The selected pure culture strain or strain are grown in a suitable fluid medium, at an optimum temperature, for an appropriate period. The pure growth is then exposed to the action of solution of Formaldehyde I.P. in suitable concentration and temperature. The product is finally filled in suitable sterilised containers which are subsequently sealed.
(b) Vaccine of Bacterial Products or Bacterial Derivatives- These vaccines are prepared by growing the organisms on suitable media and then deriving specific antigenic constituents of the bacteria by various special methods.
*Ins. by G.O.I. Notification No. GSR 659(E) dt 31.8.1994.
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(c) Living Bacterial Vaccines- They are prepared from non-pathogenic but fully immunogenic strains of micro-organism. Strict aseptic precautions are taken throughout the preparation against the introduction of microbial contaminants.
7. General Standards:-
(a) Description- Bacterial vaccines are colourless to yellowish brown liquids containing dead or viable bacteria in homogenous suspension.
(b) Identification- All types of vaccines confer active immunity in the susceptible animals which can be demonstrated by injecting suitable experimental animals with the calculated doses of the product and subsequently determining the presence of the protective antibodies in their serum and/or by challenging the vaccinated animals by injecting viru lent strain of the homologous organisms. The protected animals should survive the challenge.
(c) Test for Sterility- All bacterial vaccines shall be tested for sterility in accordance with the provision of Rules 115 to 119 (both inclusive). If the vaccine contains added bactericide or bacteriostatic, a quantity of medium sufficient to render the growth inhibitor ineffective is added to the sample, or a suitable substance is added to the sample, or a suitable substance is added in concentration sufficient to render the growth inhibitor in-effective but not itself to inhibit the growth of micro-organism.
(d) Purity Tests for Living Bacterial Vaccine- Petri-dishes containing suitable media are streaked with the final product and incubated at 37° C for 72 hours. The vaccine passes the test if no growth of micro -organisms other than those from which the vaccine was prepared is observed. Other tests include examination for motility of the organisms, fermentation reactions and thermoagglutination test and dye-inhibitor tests in case of bruceliza vaccine.
(e) Safety Test- The safety of the vaccine shall be assessed by injecting it in appropriate dose in suitable susceptible animals. No animal should show any untoward, general or local reaction, within seven days after inoculation.
(f) Potency Test- Wherever applicable, susceptible experimental animals are inoculated with the calculated doses of the final product. The animals are challenged, after the period of immunisation, with virulent infective dose of the homologous culture along with the controls. The potency of the vaccine is assessed by the survival of the vaccinated animals and the death of the controls.
8. Labelling:-
(a) The label on the ampoule or the bottle shall indicate: (i) Proper name. (ii) Contents in millilitres or doses. (iii)Potency, if any. (iv)Batch number. (v) Expiry date.
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(b) The label on the outside container shall indicate: (i) Proper name. (ii) Contents in Millilitres or doses. (iii) Batch number. (iv) Date of manufacture. (v) Manufacturing licence No. (vi) Manufacturer’s name and address. (vii) For animal treatment only”. (viii) Storage conditions.
9. Storage- Bacterial vaccines shall be stored, protected from light at temperature between 2°C to 4°C and shall not be frozen.
10. Date of manufacture- The date of manufacture shall be, unless otherwise specified in the individual monograph in this part, as defined in clause (b) of sub-rule (3) of rule 109.
Anthrax Spore Vaccine (Living)
1. Synonyms- Avirulent Anthrax Spore Vaccine or Bacillus Anthracis Vaccine (Living).
2. Definition- The vaccine is a suspension of living spores of an un-capsulated avirulent strain of B. anthracis in 50 per cent glycerine saline.
3. Preparation- Avirulent B. anthracis of known antigenicity is grown on suitable medium at pH. 7.4 in Roux flasks. After 72 hours incubation at 37° C, the pure sporulated culture growth which shows 70 to 80 per cent sporulation is washed with normal saline and glycerinated to the extent of 50 per cent by weight of the culture washing and the whole suspension is kept at room temperature for twentyone days to allow for the stabilization of the spores.
4. Standard:-
(a) Description- It is slightly opalescent or pale brown semi-viscous liquid.
(b) Identification- Uncapsulated B. anthracis which is avirulent can be isolated from the vaccine.
(c) Sterility test- Should comply with the test for sterility described in the general monograph on “Bacterial Vaccine”.
(d) Purity Test- Complies with the “Purity Tests for Living Bacterial Vaccine” described under the general monograph on “Bacterial Vaccines”.
(e) Safety Test- Four healthy adult guinea-p igs each weighing 300-450 g. not previously treated with any material which will interfere with the test are inoculated subcutaneously, two with 0.2 ml. each and two with 0.5 ml. each of the unglycerinated suspension respectively.
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Four more guinea-pigs are injected with 1:5 dilution of the glycerinated product in the same manner. No untoward reaction should be observed and none of the animals should die of anthrax during the period of observation for seven days.
(f) Safety and Potency Test in sheep and goat- Spore count of the glycerinated suspension is made after twentyone days from the date of glycerination. Three plates for each of the three dilution 10-5, 10-6 and 10-7 are made.
Eight sheep and eight goats each weighing not less than 18 kg. are injected subcutaneously in the following manner:-
two sheep : Each subcutaneously with 10 ml. of the stock suspension (for safety).
two goats : Each subcutaneously with 5 ml. of the stock suspension (for safety).
six sheep : Each subcutaneously with one million spores suspended in 50 per cent glycerine saline solution.
six goats : Each subcutaneously with one million spores suspended in 50 per cent glycerine saline solution.
None of these animals should die of anthrax. Twenty one days after vaccination, the animals are challenged with 100 lethal doses of virulent B. anthracis spores along with two healthy sheep and two goats as controls.
All the controls should die of anthrax within 72 hours after challenge and at least 66 per cent of the vaccinated animals should survive. The animals shall be observed for a minimum of ten days from the date of challenge.
[*(g) Viable Count.- The vaccine when plated on suitable media should show 10 million viable spores per cattle dose and 5 million spores per sheep dose.]
5. Labelling and Storage- Should comply with the requirements for “Labelling” and “Storage” as laid down in the general monograph on “Bacterial Vaccines”.
*[(6) Expiry Date- The date of expiry of the potency of the vaccine shall be not more than two years from the date of manufacture if stored in 4oC and six months, if stored at room temperature.]
Blackquarter Vaccine
1. Synonym- Blackleg vaccine or Quarter Evil Vaccine.
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2. Definition-Blackquarter Vaccine is a culture of Clostridium chauvoei grown in a suitable anaerobic fluid medium and rendered sterile and toxic by the addition of Solution of Formaldehyde I.P. in such a manner that it retains its immunising properties.
3. Preparation- Cultures of Cl. Chauvoei are grown in a suitable anaerobic fluid medium and killed by the addition of a suitable concentration of Solution of Formaldehyde I.P. The final product shall be adjusted to pH.7.0.
4. Standards:-
(a) Description- It is a yellowish brown liquid containing dead bacteria in suspension.
(b) Identification- It protects susceptible animals against infection with Cl. Chauvoei.
(c) Sterility Test- Should comply with the test for sterility described in the general monograph on “Bacterial Vaccine”.
(d) Safety and Potency Tests- At least six adult healthy guinea-pigs each weighing 300 g to 450 g are injected subcutaneously each with 3 ml. of the product followed a week later by a second injection with the same dose. They should not show any systemic reaction but may show only a minimum of local reaction. Fourteen days after the second injection six of the vaccinated guinea-pigs are challenged intramuscularly with 25 viable spores of Cl. Chauvoei equivalent to 5 c.h.d. along with 0.2 ml. of a 5 per cent solution of calcium chloride. Two controls are used. The controls should die of the specificinjection and at least 4 of the six vaccinated animals should survive before the product is passed for issue.
5. Labelling and Storage- Should comply with the requirements of “Labelling” and “Storage” as laid down in the general monograph on “Bacterial Vaccines”.
6. Expiry Date- The date of expiry of the potency of the vaccine shall not be more than twenty -four months from the date of manufacture.
_______________________________________________________________________ *Subs. by G.O.I. Notification No. G.S.R 659 (E) dt. 31-8-1994.
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Brucella Abortus ( Strain 19 Vaccine) (Living)
1. Synonym- Contagious Abortion Vaccine, (Strain 19) (Living).
2. Definition- Brucella Abortus (Strain 19) Vaccine (Living) is a suspension of a pure smooth living culture of Br. Abortus of low virulence in normal saline solution.
3. Preparation-Forty eight to seventy-two hour old growth of Br. Abortus (Strain 19) on potato agar medium in Roux flasks washed with buffered normal saline solution pH 6.4 and the pure growth from the flasks are pooled together, 0.5 ml. of the pooled product is mixed with 4.5 ml. of normal saline solution at pH 6.4 in graduated centrifuge tube and centrifuged at 3000 r.p.m for one hour. The percentage of cell deposit is assessed by reading the amount of cell deposit obtained.
The concentrated suspension is then diluted with buffer normal saline solution so that the final product contains 0.72 per cent bacterial cell deposit.
4. Standard:
(a) Description-It is an almost white turbid liquid containing live bacteria in suspension.
(b) Identification- It consists of Gram-negative bacilli capable of protecting susceptible animals against Brucellosis.
(c) Sterility Test- Should comply with the test for sterility described in the general monograph on “Bacterial Vaccine”.
(d) Purity Test- A smear of the finished products is examined microscopically after staining by Gram’s method for evidence of any contamination. When grown on suitable media, Br. Abortusshould be obtained in a pure state.
(e) Safety Test- Two healthy guinea-pigs each weighing 300 g to 450.g are inoculated subcutaneously each with 1.0 ml. of the final product. The guinea-pigs should not show excessive reaction of a toxic nature during the period of observation of ten days.
(f) Potency Test- Each of a group of four healthy guinea-pigs, drawn from a uniform stock and each weighing 300 g. to 450 g. is injected intra-muscularly with 1 ml. of the vaccine, and is challenged nine weeks after vaccination by the intramuscular injection of 1 ml. of a suspension containing 5,000 fully virulent Br. Abortus organisms. Each of a group of two unvaccinated guinea-pigs is similarly injected. After a further six weeks, the guinea-pigs are killed and cultures are made from their spleens. More than half of the vaccinated guinea-pigs contain no demonstrable Br. Abortus in the spleen; all the controls are infected.
(g) Viable Count- The vaccine when plated on suitable media should show between 14, 000 million and 18,000 million Br. Abortus organisms per ml. At least 80 per cent brucella organisms should be in the smooth phase.
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5. Labelling and storage- Should comply with the requirements of “Labelling” and “Storage” as laid down in the general monograph on “Bacterial Vaccines”. The liquid vaccine shall be issued fresh as far as possible without allowing any period of storage after manufacture.
6.Expiry Date- The date of expiry of the vaccine shall be not more than five weeks from the date of manufacture.
Enterotoxaemia Vaccine
1. Synonyms- Clostridium Wilchii, Type D, Formal Culture: Pulpy Kidney Vaccine.
2. Definition- Enterotoxaemia Vaccine is a culture of a highly toxigenic strain of Clostridium type D, group is an anaerobic medium rendered sterile and toxic by the addition of Solution of Formaldehyde I.P in such a manner that it retains its immunising properties.
3. Preparation- Selected toxigenic strain of Cl. Welchii type D, is grown in a liquid medium under conditions which ensure maximum epsilon toxin production. The culture is checked for purity and toxicity as tested in mice. Solution of Formaldehyde I.P. is added in suitable concentration and the formolised culture is kept at 37° till the production is sterile and non-toxic.
4. Standard -
(a) Description- It is a yellowish brown liquid containing dead bacteria in suspension.
(b) Identification- When injected into susceptible animals it stimulates the production of epsilon antitoxin of Cl. Welchii, type D.
(c) Sterility Test- Complies with the test for sterility described in the general monograph on ‘Bacterial Vaccines’.
(d) Safety and Potency Tests- At least eight sheep each weighing not less than 18 kg. or twelve rabbits each weighing 1 kg. to 1.5 kg. are used for testing the safety and potency of each brew of the vaccine. Two sheep receive subcutaneously 10 ml. each and the other six sheep receive each 2.5 ml. of the product subcutaneously. The rabbits are given subcutaneously a dose of 5 ml. each. The sheep and rabbits are observed for five days. They should show only a minimum local reaction and no systemic reaction.
The sheep receiving 10 ml. are withdrawn from experiments after five days. Each of the other six sheep is inoculated with a second dose of 2.5 ml. fourteen days after the first injection. The rabbits are inoculated with 5 ml. as a second dose, after one month of the first inoculation. The day after the second inoculation the sera of sheep or rabbits are pooled separately. The pooled serum of eac h group of animal shall contain in each ml. not less than two international units of Cl.welchii epsilon antitoxin which is determined by testing on mice as follows:
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One ml. of the pooled serum is mixed with one ml. of the epsilon toxin of Cl. welchii type D, containing 300 mouse-minimum-lethal-doses (mouse m.l.d.) and kept at room temperature for half an hour. At least two mice each weighing not less than 18 g. are each given intravenously 0.2 ml. of the mixture. As control two mice each weighing not less than 18 g. should each receive 0.2 ml. of the toxin containing 300 mouse m.l.d per ml. diluted with equal volume of normal saline. The control mice should die within 1 to 2 hours while the mice receiving the mixture of serum and toxin should survive for at least two days. Sera containing one International Unit of epsilon antitoxin per ml. will be able to neutralise 150 mouse m.l.d. of epsilon toxin of Cl. Welchii, type D.
5. Labelling and Storage- Should comply with the requirements regarding “Labelling” and “Storage” as laid down in the general monograph on “Bacterial Vaccines”.
6. Expiry Date- The expiry date of potency of the vaccine shall be not more than twelve months from the date of manufacture.
Fowl Cholera Vaccine (Polyvalent)
1. Synonym- Pasteurella Septica Vaccine (Avian).
2. Definition- Fowl Cholera Vaccine is a formolised pure broth culture of virulent strains of Pasteurella Septica (Avian).
3. Preparation- The strains are grown separately in nutrient broth for 48 hours at 37° C. The pure growth is killed by the addition of a Solution of Formaldehyde I.P in a suitable concentration. The cultures are then mixed in equal proportions and the final vaccine is bottled in suitable containers.
4. Standard -
(a) Description- It is a yellow liquid containing dead bacteria in suspension.
(b) Identification- It protects susceptible birds against P. aviseptica infection.
(c) Sterility test- Complies with the test for “Sterility” described under the general monograph on “Bacterial Vaccines”..
(d) Safety Test- Two healthy young fowls each weighing not less than 400 g. or twelve healthy mice are innoculated subcutaneously each with 1 ml. of the final product. The birds should not show any untoward reaction during the period of observation for seven days.
5. Labelling and Storage- Should comply with the requirements of “Labelling” and “Storage” as laid down in the general monograph on “Bacterial Vaccines”.
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6. Expiry Date- The date of expiry of potency of the Vaccine shall be not more than six months from the date of manufacture.
Hemorrhagic Septicaemia Adjuvant Vaccine
1. Synonym- Pasteurella Septica Adjuvant Vaccine.
2. Definition- The vaccine is a homogenous suspension of formolised agar-washed Pasteurella septica with liquid paraffin and lanolin.
3. Preparation- Pure growth of a highly antigenic strain of P. Septica in phase 1 grown on nutrient agar medium containing 0.5 per cent yeast extract is washed with 0.5 per cent formol saline. The pooled suspension is diluted with normal saline to contain approximately 2100 million P. Septica organisms per ml. The safety test of this adjusted suspension is conducted on four white mice each weighing not less than 18 g. and observed for three days before it is mixed with liquid paraffin and lanolin in suitable proportion.
The mixture is blended until a homogenous emulsion is obtained which is filled in sutaibale containers.
4. Standard-
(a) Description- It is a white thick oily liquid containing dead bacteria in suspension.
(b) Identification- It protects susceptible animals against infection with P. Septica.
(c) Sterility Test- It complies with the test for “Sterility” described in the general Monograph on “Bacterial Vaccines”.
(d) Safety Test- S ix white mice each weighing not less than 18 g. are inoculated intraperitoneally each with 0.5 ml. of the vaccine. None of the mice should die of pasteurellosis during the observation period for seven days.
(e) Potency Test- Three susceptible calves in good condition between the ages of nine months to three years are injected intramuscularly, each with 2 ml. of the vaccine, in the case of animals weighing upto 140 kg. and 3 ml. for heavier ones.
Three weeks later these animals along with two healthy animals of the same type and species are challenged subcutaneously with 18 hours old broth culture of P. Septica equivalent to at least 50 million mouse minimum infective dose. Both the controls should die of pasteurellosis and at least two out of the three protected animals should survive the challenge dose for a period of seven days.
5. Labelling and storage- Should comply with the requirements for “Labelling” and “Storage” as laid down in the general monograph on “Bacterial Vaccines”.
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6. Expiry Date- The date of expiry of potency of the vaccine shall be not more than twelve months from the date of manufacture.
Haemorrhagic Septicaemia Vaccine (Broth)
1. Synonym- Pasteurella Septica Vaccine (Broth).
2. Definition- Haemorrhagic Septicaemia Vaccine is formolised culture of a virulent strain of Pasteurella septica in nutrient broth.
3. Preparation- P.Septica culture is grown in nutrient broth at 37°C. The pure growth is killed by the addition of a solution of Formaldehyde I.P. in a suitable concentration.
4. Standard -
(a) Description- It is a pale yellow liquid containing dead bacteria in suspension.
(b) Identification- It protects susceptible animals against infection with P.Septica.
(c) Sterility Test- Complies with the test for “Sterility” described under the general monograph on “Bacterial Vaccines”.
(d) Safety Test- Four healthy rabbits each weighing 1 kg. to 1.5 kg. are inoculated subcutaneously each with 5 ml. of the product. There should be no untoward reaction during the period of observation for seven days. Alternately two rabbits and six mice may be employed. The dose for mice will be 0.5 ml.
5. Labelling and Storage- Should comply with the requirements of “Labelling” and “Storage” as laid down in the general monograph on “Bacterial Vaccines”.
6. Expiry Date- The date of expiry of potency of the vaccine shall be not more than six months from the date of manufacture.
Salmonella Abortus Equi Vaccine
1. Synonym- Equine Abortion Vaccine.
2. Definition- Equine Abortion Vaccine is a mixture of equal parts of pure formolised cultures of smooth laboratory strains of Salmonella abortus equi.
3. Preparation- The strains are grown separately on plain agar in Roux flasks, for 24-28 hours at 37° C. The pure growth is washed with normal saline solution and the washings are pooled together. The suspension is standardised to contain approximately 600 million Sal.abortus equi organisms per ml. using normal saline solution as diluent. The culture is killed by the addition of sufficient quantity of solution of Formaldehyde I.P in a suitable concentration and the product is kept at 37° C for seven days. Potassium alum is added to give a final concentration of 1 per cent
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4. Standard-
(a) Description- It is an opalescent liquid containing dead bacteria in suspension.
(b) Identification- It protects susceptible animals against infection with Salmonella Abortus equi.
(c) Sterility Test- Complies with the test for sterility described in the general monograph on “Bacterial Vaccines”.
(d) Safety Test- Six white mice each weighing not less than 18 g. are inoculated intraperitoneally each with 0.5 ml. of the product. None of the mice should die of salmonellosis. The mice are observed for ninety-six hours.
3. Labelling and Storage- Should comply with the requirements for “Labelling” and “Storage” as laid down in the general monograph on “Bacterial Vaccines”.
4. Expiry Date- The date of expiry of potency of the vaccine shall be not more than six months from the date of manufacture.
Streptococcus Equi Vaccine.
1. Synonym- Strangles Vaccine
2. Definition- Streptococcus equi Vaccine is a phenolised culture of a number of different isolates of Streptococcus equi in glucose serum broth.
3. Preparation- Equal proportions of forty-eight hours old pure cultures of different isolates of Str. Equi in serum glucose both are mixed together. The suspension is centrifuged and the deposit is washed with normal saline solution after removing the supernatant. The washed cells are suspended in normal saline and heated in a water bath 65°C for two hours. Phenol and normal saline are added to give a final concentration of 1200 million Str. Equi organisms per ml. and 0.5 per cent of phenol in the vaccine.
4. Standard -
(a) Description- It is a slightly opalescent liquid containing dead bacteria in suspension.
(b) Identification - It protects susceptible animals against infection with Str. Equi.
(c) Sterility Test- Complies with the test for “Sterility” described in the general monograph on “Bacterial Vaccines. The nutrient broth being replaced by glucose broth.
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(d) Safety Test- Two ponies and two rabbits (each weighing not less than 1 kg.) are inoculated each with 10 ml. and 2 ml. respectively of the final product. The animals should not show any untoward reaction during the period of observation of seven days.
5. Labelling and Storage- Should comply with the requirements for “Labelling” and “Storage” as laid down in thegeneral monograph on “Bacterial Vaccines”
6. Expiry Date- The date of expiry of potency of the vaccine shall be not more than six months from the date of manufacture.
Old Adjuvant Vaccine against Pasteurellosis in Sheep and Goats.
1. Synonym- Pasteurella Septica Adjuvant Vaccine for ovines and Caprines.
2. Definition- The vaccine is a homogenous suspension of formolised agarwashed Pasteurella septica of ovine origin with liquid paraffin and lanolin.
3. Preparation- Pure growth of highly antigenic strains (R1, R2, R4) in phase I grown separately on nutrient agar medium containing 0.5 per cent yeast extract is washed with 0.5 per cent Normal saline. Equal quantities of the suspension of three strains diluted with Normal saline to contain approximately 2100 million organisms per ml. is pooled together. The safety test of this adjusted pooled suspension is conducted in for white mice each weighing not less than 18 g. and observed for three days before it is mixed with liquid paraffin and lanolin in suitable proportion.
The mixture is blended until a homogenous emulsion is obtained which is filled in suitable containers.
4. Standards- (a) Description- It is a white thick oily liquid containing dead bacteria in suspension.
(b) Identification- It protects susceptible animals against infection with P.Septica.
(c) Sterility Test- Complies with the test for sterility described in the general monograph on “Bacterial Vaccines”.
(d) Safety Test- Six white mice each weighing not less than 18 g. are inoculated intra- peritoneally each with 0.5 ml. o the vaccine. None of the mice should die of Pasteurellosis druing the observation period of seven days.
The vaccine is also inoculated into six sheep and six goats in a dose of 3 ml. each intramuscularly and are observed for a period of seven days. During this period none should die of Pasteurellosis.
(e) Potency Test- Not being done at present.
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5. Labelling and Storage- - Should comply with the requirements for “Labelling” and “Storage” as laid down in the general monograph on “Bacterial Vaccines.
6. Expiry Date- The expiry date of Potency of the Vaccine shall be not more than twelve months from the date of manufacture.
*[Multicomponent of Clostridial Vaccine
1. Synonyms. – Combined anaculture of Clostridium perfringens type C and D, C1. septicum and CI. oedematies.
2. Defination – It consists of four highly antigenic components containing the toxoids of C. perfringens type D, CI. Perfringens type C, oedematiens and CI. Septicum which are prepared in double strength and then combined in such a proportion that would invoke adequate anti-toxin response in the vaccinated sheep against each antigen incorporated in the vaccine
3. Preparation – The above strains are grown separately in suitable liquid media under conditions which ensure maximum toxin production. The cultures are checked for purity and toxicity in mice. Solution of Formaldehyde I.P. of analytical grade is added to a 0.5 per cent frinal concentration and formalized cultures are kept at 37oC till the product is sterilized and atoxic. The formalized anacultures are pooled, precipitated by the addition of Aluminium Chloride, 20 per cent solution in distilled water to have a final concentration of the chemical to 10 per cent and pH adjusted to 6.0.the sedimented toxoid is reconstituted to have its original volume in normal saline.
4. Standards :- Description – It is whitish liquid when shaken thoroughly to contain killed bacteria and toxoid in suspension.
(a) Identification – When injected to susceptible animals it stimulates the production of epsilon and beta antitoxins against CI. Perfrigens type D and C and also antitoxins against CI. Septicum and toxin of CI. Oedematiens.
(b) Sterility Test – Complies with the test of sterility described in general monograph on “Bacterial Vaccines.”
(c) Safety Test – Four sheeps each are inoculated with 10ml. S/C of the product and these are observed for 7 days during which period animals shall not show any local or systemic reaction.
(d) Potency Test – Eight sheep each are inoculated with 2 doses of vaccines S/C at an interval of 21 days and bled on 10th day after 2nd inoculation for collection of serum for assessing the antitoxin titre against each antigen incorporated in the vaccine. The post- inoculation serum should contain ________________________________________________________________________ *Ins. by G.O.I. Notification GSR No. 659(E) dt 31-8-1994.
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(e) not less than 2 i.u. of epsilon and beta antitoxins of CI. Perfringens and 2.5 i.u. of CI. Septicum antitoxin and 4 i.u. of CI. Oedematiens antitoxin.
5. Labelling and storage - Shall comply with the requirements regarding labeling and storage as laid down in the general monograph on “Bacterial Vaccines”.
6. Expirty date – The expiry date of potency of vaccine shall not be more than 6 months from the date of manufacture.
Haemorrhagic Setocaemia Vaccine – Alum Treated
1. Synonyms – Pasterulla multocida/(Yersinia Multocida) vaccine – Alum treated.
2. Defination -- The vaccine is a formalized culture of a virulent strain of Pasteurella multocida in nutrient broth treated with potash alum.
3. Preparation -- A highly potent strain of Pasteurella multocida type I in Phase I is grown on nutrient broth at 37oC. The pure growth is killed by the addition of a solution of Formalin I.P in suitable concentration (0.5 per cent). This is treated with Potassium Alum I.P to give a final concentration of 1 per cent.
4. Standard – (a) Description – It is a white suspension containing dead bacteria and alum.
(b) Identification – It protects susceptible animals against infection with P.multocida.
(c) Sterility Test -- It complies with the test for sterility described under general monograph on “Bacterial Vaccines:.
(f) Safety Test -- Four healthy rabbits each weighting 1 to 1.5 kg. Are inoculated subcutaneously each with 5 ml. of the product. There shall be no untoward reaction during the period of observation for 7 days except slight local welling. Alternatively two rabbits and six mice may be employed. The dose for mice will be 0.5 ml.
5. Labelling and Storage :-- Shall comply with the requirements of labeling and storage as laid down in the general monograph on “Bacterial Vaccines”.
6. Expiry date – The date of expiry of potency of the vaccine shall be not more than six months from the date of manufacture.]
(B) PROVISIONS APPLICABSLE TO THE PRODUCTION OF VIRAL VACCINES.
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1. Definition- (i) This part of the Schedule applies to viral vaccines live or inactivated made from any virus pathogenic to domestic animals and poultry and made from other modified viruses which have any antigenic value.
(ii) For the purpose of this part of the Schedule, a virus vaccine means a sterile suspension or a freeze dried powder containing the modified living or inactivated virus particles, which in its original unaltered stage, causes disease from which the vaccine derives i8ts name and which has been prepared from the blood or tissues of a suitable host in which it has been grown in vivo or from tissue culture.
2. Staff of Establishment- The establishment in which viral Vaccines, are prepared, must be under the direction and control of an expert in bacteriology with specialized training in virology and sufficient experience in the production of viral vaccines, and he shall be assisted by a staff adequate for carrying out the tests required during the preparation and standardisation of the vaccine.
3. Proper Name- The proper name of any viral vaccine shall be the name of the disease which is caused by the particular virus from which the vaccine is produced followed by the word “Vaccine” unless the Schedule otherwise provides, if there is no special provision in the Schedule such other name as is approved by the Licensing Authority. Provided that in the case of the undermentioned preparations the proper name of the vaccine shall be as follows:-
(i) Fowl Pox Vaccines, Chick Embryo Virus (Living). (ii) Fowl Pox Vaccine, Pigeon Pox Virus (Living). (iii) Horse Sickness Vaccine (Living) (iv) Ranikhet Disease Vaccine (Living) (v) Ranikhet Disease Vaccine F Strain (Living) (vi) Rinderpest Goat Adapted Tissue Vaccine (Living) (vii) Rinderpest Lapinised Vaccine (Living) (viii) Rinderpest Lapinised Avianised Vaccine (Living) (ix) Sheep and Goat Pox Vaccine (Living) (x) Swine fever vaccine (crystal violet) (xi) Swine fever vaccine lapinised (Living). *[(xii) Foot and Mouth Dieses Vaccine (Inactivated) (xii) Canine Hepatitis Vaccine (Living)]
*[4. Records- The seed virus used in the preparation of vaccine shall, before being used for preparing a batch, be thoroughly tested for purity, safety, sterility and antigenicity by the generally accepted tests applicab le to a particular virus. It shall not be more than five passages away from the stock seed virus, unless otherwise system at specified passage level and tested for bacterial, mycoplasmal and extraneous viral contamination. The permanent record which the licensee is required to keep shall include a record of the origin, properties and characteristics of the seed virus from which the vaccines are made.] _______________________________________________________________________ *Ins./Subs. by G.O.I. Notification No. GSR 659(E) dt 31-8-1994.
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5. Tests- Viral vaccine shall be tested for sterility, safety and potency on suitable test animals and for viability in the case of live vaccines.
(a) Sterility Test- All vaccines shall be tested for sterility in accordance with rules 115 to 119. If the vaccine contains added bactericides or bacteriostatic, a quantity of medium sufficient to render the growth inhibitor ineffective is added to the sample or a suitable substance is added in a concentration sufficient to render the growth inhibitor ineffective but not itself to inhibit the growth of microorganisms.
(b) Safety Test- Suitable laboratory animals or large animals or birds may be employed to test the vaccine for safety. Details of the safety test are given in the individual monograph.
(c) Potency Test- All virus vaccines for which potency test has been prescribed shall be tested for potency and only those which pass the potency test shall be issued. Details of the potency test are given in the individual monograph.
6. Storage- Live viral vaccines shall be stored, protected from light at sub-zero temperature as required. Other viral vaccines shall be stored at 2 ° C to 4 ° C but shall not be frozen.
7. Condition of housing of animals- (i) The animals used in the production of vaccine must be housed in hygienic conditions in premises satisfactory for this purpose.
(ii) Only healthy animals may be used in the production of vaccine. Each animal intended to be used as a source of vaccine must, before being passed for the production of vaccine be subjected to a period of observation in quarantine for at least seven days. During the period of quarantine the animal must remain free from any sign of disease and must be well kept.
[*(iii) The poultry birds from which eggs and cell culture for production of vaccines are obtained should be housed in a manner so as to keep them free from extraneous infection and shall be screened at frequent intervals for common bacterial, mycoplasmal and viral infection. The record of the tests and their results shall be maintained by the manufacturers.]
8. Labelling- The provisions of “Labelling” as laid down for Bacterial Vaccines shall also apply to Viral Vaccines. The following additional information shall also be included on the label of the outside container.
(i) The name and percentage of bacteriostatic agent contained in the vaccine.
(ii) If the vaccine as issued for sale contains any substance other than the diluent, the nature and strength of such substance.
9.Date of Manufacture- For the purpose of this part of the Schedule, the date of manufacture shall be what is given unless otherwise stated in the individual monograph, as defined in sub-clause (b) of sub-rule (3) of rule 109.
_______________________________________________________________________ *Ins. by G.O.I. Notification No. GSR 659(E) dt 31-8-1994.
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Fowl Pox Vaccine Chick Embryos Virus (Living)
1. Synonym- Egg adapted Fowl Pox Vaccine (Living)
2. Definition- Fowl-pox vaccine, Chick-Embryo Virus (Living) is a suspension of a modified living virus (e.g. Mukteswar Strain) prepared from the chorioallantoic membrane (CAM) of the infected embryo and is either freeze dried or is issued as glycerinated liquid vaccine.
3. Preparation- Active chick-embryos obtained from Salmonella pullorum free flock, are used. *[Twelve to thirteen days old embryos are injected with a suitable dilution of the suspension of the infected membrane (seed virus) of chick embryo adopted fowl pox virus.] The suspension of the stock seed virus is dropped on the CAM. After an incubation at 37°C for a suitable period membranes showing discrete or confluent lesions (pocks) are harvested. These are homogenised with adequate quantity of antibiotics (penicillin and streptomycin) ampouled in 0.5 ml. quantities and freeze dried.
4. Standard -
(a) Description- Light mauve coloured scales.
(b) Identification- When reconstituted vaccine is applied to scarified area of the skin of a fowl it produces characteristic lesions of fowl pox. This product should afford protection against fowl pox.
(c) Moisture Content- Moisture Content in the finished product should not exceed 1.0 per cent.
(d) Safety Test- For testing each batch of fowl pox vaccine twelve healthy cockerels, or other suitable young chicken each weighing not less than 400 g. from the same source are taken. This group of twelve birds is immunized at least twenty-one days previous to the test, with fowl pox vaccine. The vaccine under test is reconstituted in 5 ml. of 50 per cent glycerine saline and administered to fowls as follows:-
Three of the test birds are injected subcutaneously with 0.8 ml. or 10 times the field doses of the vaccine under test. This group serves to indicate whether the product is free from other viruses and bacteria causing septicaemia or not.
Three of the test birds are injected intratrecheally with 0.3 ml. or 10 times the field dose of vaccine under test. This group serves to indicate whether the product is free from the virus of infectious laryngotracheitis and similar disease.
Three of the test birds are injected intranasally with 0.2 ml. of the vaccine under test. This group serves to indicate whether the product is free from the virus of Coryza and similar disease. ________________________________________________________________________ * Amended by G.O.I. Notification No. GSR 659(E) dt 38-8-1994
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The three remaining birds serve as controls. They are isolated and kept under observation for twenty-one days. The birds that succumb during the period of twenty-one days are subjected to a careful postmortem examination. The product is withheld from issue until the vaccine and the test birds are shown to be free from the causative agents of any extraneous disease.
(e) Sterility test- Complies with the tests for sterility as described under the general monograph on “viral vaccines”.
(f) Potency Test- For testing of potency three unsusceptible birds each weighing not less than 400 g. are vaccinated using the field dose by the stick method and examined for “takes”. Three weeks after vaccination these birds along with two unvaccinated controls are exposed to challenged virus and observed for fourteen days. The vaccinated birds should not manifest any reaction, while he controls should show active “takes”.
5. Labelling- Should comply with the requirement for “Labelling” as laid down in the general monograph on “Viral Vaccines”.
6. Storage and Expiry date- Freeze dried vaccine shall be expected to retain its potency for periods at temperatures as specified below:-
-15 ° C to - 20° C- Twenty four months. 2° C to 4 °C - Twelve months. Room temperature upto one month.
The liquid vaccine shall be expected to retain its potency for periods and temperatures as specified below:-
2° C to 4 °C – six months. Room temperature- seven days.
Fowl- Pox Vaccine Pigeon Virus (Living)
1. Synonym- Fowl Pox Vaccine (Pigeon pox scab).
2. Definition- Fowl vaccine, pigeon- pox virus (living) consists of pigeon pox virus in scabs collected from artificially infected pigeons and dried.
3. Preparation- Healthy pigeon are scarified on the legs and breast, with a suitable dilution of the suspension of pigeon-pox virus. The pigeons reacting satisfactorily and showing good takes are selected and the superficial skin layer scraped by means of sharp scalpel. The material so collected is freed from feathers, homogenised and dried or freeze dried. The dried pulp is powdered, sieved and ampouled in 0.3 g. quantities and sealed
4.. Standard-
(a). Description- Light cream coloured powder.
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(b).Identification- When applied to feather follicles by vigorous rubbing, it produces mild reaction in fowls. The product should afford protection to fowls upto six weeks against fowl pox.
(c).Safety Test- For testing a batch of vaccine, twelve healthy cockerels, or other suitable young chicken from the same source are made available at the same time. This group of twelve birds is immunised at least twenty -one days previous to the test with fowl pox vaccine. The vaccine under test is reconstituted in 10 ml. of 50 per cent glycerine saline and administered to fowls as follows: -
Three of the test birds are injected subscutaneously with 0.3 ml. or 10 times the field dose of the vaccine to be tested. This group serves to indicate whether the product is free from organisms of septicaemia disease.
*[Three of the test birds are injected intrathicheally with 0.2ml of 10 times of the field dose of the vaccine under test. This group serves to indicate whether the product is free from the virus of infectious laryngotracheitis and similar diseases.]
Three of the test birds are injected intranasally with 0.2 ml. of the vaccine to be tested. This group serves to indicate whether the product is free from virus of Coryza and similar diseases.
The three remaining birds serve as controls. All the birds under test are isolated and held under observation for twenty-one days. All those that succumb are subjected to careful post- mortem examination. The product is withheld from issue until the vaccine and test birds are shown to be free from the causative agents of any extraneous diseases.
(d) Sterility Test- Complies with the tests for sterility described, under the general monograph on “Viral Vaccines”.
(e) Potency Test- For testing the potency of a batch of vaccines three susceptible birds each weighing not less than 400 g. are vaccinated using the field dose by the follicular method and examined for ‘takes’. Three weeks after vaccination these birds and two healthy susceptible controls are exposed to challenge virus and are observed for fourteen days. The vaccinated birds shall manifest no reaction, while the controls must have active “takes”.
5. Storage and Labelling- Should comply with the requirements of ‘Labelling’ as laid down in the general monograph on ‘Viral Vaccines’.
6. Expiry date- The vaccine shall be expected to retain its potency for periods at temperature as specified below:-
--15 ° C to - 20 °C--- two years. 2° C to 4 °C --- twelve months. Room temperature- Upto one month.
________________________________________________________________ *Ins. by G.O.I. Notification No. GSR 659(E) dt 31-8-1994.
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Fowl Pox Vaccine- Pigeon Pox- Chick Embryos Virus (Living)
1. Synonym- Chick embryo adapted pigeon pox vaccine (Living)
2. Definition- Fowl pox vaccine (Pigeon Pox virus) chick embryo adapted virus (living) is a suspension of a modified living virus prepared from he chorioallantoic membranes of the infected embryos and is freeze dried.
3. Preparation- Active chick embryos obtained from Salmonella Pullorum free stock are used. Twelve to thirteen days old embryos are injected with a suitable dilution of the suspension of the infected membrane (stock seed virus) of chick embryo adapted pigeon pox virus. The suspension of the stock seed virus is dropped on the membrane. The inoculated eggs are incubated at 37 ° C for four days. One of the fourth day embryos that are living, are removed to a refrigerator for chilling for about one hour. Membranes showing discrete lesions (Pocks) are harvested. These are homogenised with adequate quantities of antibiotics, ampouled in 0.5 ml. quantities and freeze dried.
4. Standards-
(a) Description- Light mauve coloured scales.
(b) Identification- When reconstituted vaccine is applied to scarified area of the skin of a fowl, it produces characteristics lesions of Fowl Pox. This product should afford protection against pox.
(c) Moisture content- Moisture content in the finished product should not exceed 1.0 per cent.
(d) Safety test- For testing each batch chicks aged four to six weeks from the same source are taken. This groups of twelve birds is immunised at least twenty-one days previous to the last, with fowl-pox vaccine. The vaccine under test is reconstituted in 3 ml. of normal saline solution and administered as under:-
Three of the test chicks are injected subcutaneously with 0.3 ml. or 10 times the field dose of the vaccine under test. This group serves to indicate whether the product is free from other viruses and bacteria causing of septicaemia or not.
Three of the test chicks are injected intra-tracheally with 0.3 ml. or ten times the field dose. This group serves to indicate whether the product is free from the viruses of infections laryngeotracheiti and similar diseases.
Three of the test chicks are injected with 0.2 ml 1/N of the vaccine under test. This group serves to indicate whether the product is free from the virus of coryza and similar diseases.
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For remaining three chicks serve as controls. They are isolated and kept under observation for twenty-one days. The birds that succumb during the period of observation are subjected to careful post-mortem examination. The product is withheld from issue until the vaccine and the test birds are shown to be free from the causative agents of any extraneous disease.
In addition to the above, similar groups of pigeons aged six to nine months old are also injected in a similar in a similar way to eliminate psittacosis.
(e) Sterility Test- Should comply with the tests for sterility described under the general monograph on ‘Viral Vaccine’.
(f) Potency test- For testing potency of a batch of vaccine three susceptible chicks of three to four weeks of age are vaccinated by feather forthicle method ( a few forthicles on one leg are injected) and these are examined for ‘takes’.
Three weeks after vaccination these chicks along with two unvaccinated chicks are exposed to challenge virus (virulent fowl pox virus) and observed for fourteen days. The vaccinated chicks should not manifest any reaction while controls should show active ‘takes’.
5. Labelling- Should comply with the requirements for ‘Labelling’ as laid down in the general monograph on ‘Viral Vaccines’.
6 Storage- The Freeze dried product is expected to retain its potency for periods and temperatures as specified below:-
-15 ° C to 20 ° C- two years 2° C to 4 ° C- twelve months.
Room temperature- up to one month.
Sheep Pox Vaccine (Living)
1. Synonym- Sheep Pox vaccine; Goat pox vaccine.
2. Definition- Sheep pox vaccine consists of sheep pox virus collected from sheep artificially infected with sheep pox virus and freeze dried.
3. Preparation- Healthy yearling sheep are infected artificially by subcutaneous infection on the undersurface of the previously shaved abdomen with 200- 300 cc. of the freeze dried sheep pox virus (seed material) diluted in 1 : 1 Normal saline solution. On the sixth or seventh day after injection oedematous swelling develops in the injected area with thermal reaction. The sheep which develop good swelling are slaughtered and the gelatinous material present under the skin in the infected area is collected under sterile conditions. This material is mixed with 2 parts by volume of sterile peptone broth of pH 7.2 and homogenised. The homogenised suspension is filtered, ampouled in 0.5 ml. quantities and freeze dried.
4. Standard -
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(a) Description- White scales.
(b) Identification- Reconstituted vaccine when applied over the scarified area of the skin of the abdominal region of sheep will produce characteristic local lesion of pox.
(c) Moisture content- The moisture content should not exceed 1.0 per cent.
(d) Safety test- Two rabbits each weighing not less than 1 kg. are injected subcutaneously each with 1 ml. of 1 : 100 dilution of the vaccine in normal saline solution. These animals are observed for fourteen days. These animals are observed for fourteen days.
(e) Sterility Test- Complies with the tests for sterility described under the general monograph on ‘Viral Vaccines’.
(f) Potency Test- Four yearling sheep are vaccinated on the inner surface of the ear by scarification method. The contents of one ampoule of F.D. Sheep Pox vaccine are constituted in 10 cc. of 50 % glycerin saline solution, characteristic takes develop in the scarified area with ulceration and scab formation. Three weeks later these and two more susceptible sheep (Controls) are challenged by scarifying with a suspension of the previous brow of the vaccine of the undersurface of the abdomen. The controls should develop typical lesions of pox and the vaccinated should remain normal.
(g) Labelling- Should comply with the requirements of ‘labelling’ as laid down in the general monograph in ‘Viral Vaccine’.
(h) Storage and expiry date- The vaccine is expected to retain potency for period and temperature as specified below:-
-15 ° C to – 20 ° C- two years 2 ° C to 4 ° C- three months. Room temperature- Fifteen days.
Horse Sickness Vaccine (Living)
1. Synonym- African Horse Sickness Vaccine, Mouse adapted Polyvalent Horse Sickness Vaccine (Living).
2. Definition- Horse sickness vaccine is a suspension of live mouse adapted strains of Horse Sickness Virus (onderstepoort) prepared from the brains of infected mice and is freeze dried.
3. Preparation- Thirty to thirty- five days old white mice are infected intracerebrally with 0.005 ml. of a suitable dilution of the seed virus (6 or 7 types, as the case may be). Groups of large numbers of mice are injected separately with each type of the virus and are housed at 27 ° C to 32 ° C. A majority of these become paralytic on the third and fourth day when they are sacrificed and their brains collected and stored at – 15 ° C to – 20 ° C till the day of processing. For preparing the polyvalent vaccine, equal number of brains collected from mice infected with different types of the virus are homogenised with 5-10 times its volume of
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sterile lactose buffer medium (pH 7.2 )containing antibiotics. The suspension is centrifuged at 1500 r.p.m. for five minutes. The supernatant liquid is distributed in ampoules in suitable quantities and freeze dried.
4. Standard-
(a) Description- White scaly material.
(b) Identification- This product affords protection to horse against horse sickness.
(c) Safety Test- Four healthy mice thirty to thirty-five days old are injected intraperitoneally with 0.2 ml. of 10:1 dilution of the vaccine and kept under observation for ten days. All the mice should remain normal throughout the period of observation.
(d) Sterility Test- Should comply with the test for sterility described under the general monograph on ‘Viral Vaccine’.
(e) Viability Test- Each batch of vaccine is titrated in tenfold dilutions using four mice of thirty to thirty-five days old for each dilution. Each mouse is injected intracerebrally with 0.05 and kept under observation for ten days. Mortality and survival ratios are noted and Ld 50 is determined. The minimum acceptable titre is 10-4 Ld 50 per 0.05 ml.
(5) Labelling - Should comply with the requirements of ‘labelling’ as laid down in the general monograph in ‘Viral Vaccine’.
(6) Storage- The vaccine may be expected to retain its potency for twelve months if stored - 15 ° C to – 20 ° C and about six months if stored in refrigerator at 2 ° C to –4° C.
Rabies Vaccine (Inactivated)
1. Synonym- Antirabic Vaccine (Inactivated)
2. Definition- Rabies vaccine is a suspension of the brain tissue of animals, that have been infected with a suitable strain of rabies fixed virus, inactivated with phenol or some other suitable agent.
3. The following particulars relating to this vaccine are the same as those relating to Antirabic vaccine described in Part D of Schedule F to these rules, namely:-
(i) Strain of fixed Rabies Virus to be used; (ii) Staff of Establishment; (iii) Condition and housing of animals; (iv) Precaution to be observed in preparation; (v) Records; (vi) Issue.
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4. Preparation- Healthy sheep or any other suitable species of animal are inoculated subdurally or intracerebrally with an appropriate dose of suspension of a suitable strain of rabbit brain passaged rabies fixed virus. The sheep or animals which get paralysed from the sixth day onwards after the inoculation are sacrificed and their brains collected aseptically. Brain tissue is weighed individually and a suspension of suitable concentration of brain tissue prepared in buffered saline is strained through gauze. The suspension treated with phenol or some other suitable inactivating agent is incubated for an appropriate period.
5. Standard -
(a) Description- A grey to pale yellow opalescent suspension.
(b) Identification- Appropriate doses protect mice against subsequent intracerebral inoculation with suitable strain of fixed rabies virus.
(c) Safety test- Not less than five mice, each weighing at least 18 gm., are inoculated intracerebrally with not less than 0.03 ml. of the suitably diluted vaccine. None of the animals should show symptoms of rabies or die of the disease during period of observation of three weeks.
(d) Sterility Test- Should comply with the test for sterility described under the general monograph on ‘Viral Vaccine’.
6. Labelling- Should comply with the requirements of ‘Labelling’ as laid down in the general monograph on ‘Viral Vaccin es’. In addition the label in the container shall indicate the percentage of brain tissue present in the vaccine.
7. Storage- The vaccine may be expected to retain its potency for about six months if stored in refrigerator at 2° to 4 ° C.
Rabies Vaccine (Living)
1. Definition- Rabies vaccine (living) is a freeze-dried suspension of chick-embryo tissue infected with a suitable attenuated strain of rabies virus.
2. Preparation- It may be prepared by the following method. Seed virus consisting of a suspension of the Flury or other suitable strain of chick adapted virus that has been maintained by passage in chick embryos is injected into the yolk-sacs of fertile eggs incubated for a suitable period. After incubation for a further ten days, the embryos are harvested and ground in water for injection to give 33 percent suspension. The suspension is centrifuged to remove coarse particles and the supernatant fluid is distributed into ampoules in 3 millilitre quantities, and freeze dried. The vaccine is reconstituted immediately before use by adding 3 millilitres of water for injection to the contents of an ampoule.
3. Standard - It complies with the requirements of general standard of viral vaccines for abnormal toxicity, sterility, and labelling with the following additions.
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(a) Description- Dry honey-coloured flakes or powder, readily dispersible in water.
(b) Identification- It protects guinea pig against a subsequent inoculation of rabies street virus. It is distinguished from the inactivated Rabies vaccine by its ability to produce rabies encephalitic on intracerebral injection into mice.
(c) Safety- The guinea pigs used in the test for potency should not show any marked local or systemic reaction during the three weeks following injection with the vaccine.
(d) Sterility Test- Complies with the tests for sterility described under the general monograph on ‘Viral Vaccine’.
(e) Potency Test- The contents of an ampoule are dispersed in water for injection to give a 5 per cent suspension and not fewer than twenty guinea pigs, drawn from a uniform stock and each weighing 350 g. to 500 g., are each injected intramuscularly with 0.25 ml. of this suspension. Three weeks later, these guinea pigs and an equal number of similar unvaccinated control guinea pigs are each inoculated with 0.1 ml. of a suitable dilution of canine salivary gland suspension of street virus which is maintained as a 20 per cent suspension at 70 ° C or lower. The guinea pigs are observed for thirty days; not less than 80 per cent of the control guinea pigs die of rabies and not less than 70 per cent of the vaccinated guinea pigs are protected.
4. Storage- Freeze-dried vaccine should be stored at refrigeration temperatures of 2 ° C to 4 ° C.
5. Labelling- The life of the vaccine at room temperature and at refrigeration temperature should be stated on the label.
6. (a) Action and uses- Rabies vaccine (living) is used for the prophylactic inoculation of dogs against rabies; one injection should provoke a serviceable immunity lasting for at least a year. The vaccine has been used to a limited extent on cattle.
(b) Dose- By intramusclar injection: Dogs, the contents of one ampoule reconstituted in 3 ml. of water for injection; cattle five times the dog dose.
Ranikhet Disease Vaccine (Living)
1. Synonym- New castle Disease Vaccine (Living); pheumoenteritis Vaccine (Living).
2. Definition- Ranikhet Disease vaccine is a suspension of a modified living virus e.g. (Mukteswar strain) prepared from infected embryos and fluids and is freeze dried.
3. Preparation- Good fertile eggs obtained from Salmonella pullorum free flock are incubated in an egg incubator. Ten days old vigorous embryos are infected with 0.1 ml. of a suitable dilution of a suspension of the virus. Inoculation is done in the allantoic cavity. Embryos are incubated at a suitable temperature. Eggs showing dead embryos twenty-four hours after incubation are discarded. After forty-eight hours incubation the eggs are candled
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and those showing dead embryos are chilled for a suitable period of time, while embryos alive beyond forty-eight hours are discarded. The fluids and embryos are then collected and spot haemogglutination carried out. The material is homogenised in a blender and ampouled in aliquots of 0.5 ml. quantities and freeze-dried.
4. Standards-
(a) Description- Light brown scales.
(b) Identification- This product affords protection to fowls against Ranikhet Disease.
(c) Safety Test- For testing each batch of freeze dried Ranikhet Disease Vaccine, twelve healthy young chickens, all from the same source each weighing not less than 400 g. are taken and immunised against Ranikhet Disease. Fourteen days later, these birds, are tested as follows with the contents of one ampoule suspended in 100 ml. of normal saline.
Three of the test birds are injected intratracheally with 0.1 ml. equivalent to ten times the field dose of the vaccine to be tested. This group serves to indicate whether the product is free from viruses or organisms of speticaemia disease.
Three of the test birds are injected intratracheally with 0.1 ml. equivalent to ten times the field dose of he vaccine to be tested. This group serves to indicate whether the product is free from the virus of infectious laryngotracheitis, *[ ] and similar diseases.
The three remaining birds serve as controls.
**[Three of the test birds are injected intranasally with 0.2ml of the vaccine to be tested. This group serves to indicate whether the product is free from virus of Coryza and sim ilar diseases.]
All the treated birds and controls are observed daily for fourteen days. All the test birds that succumb are subjected to careful postmortem examination. The product is not issued until the birds under test are shown to be free from the causative agents of any extraneous diseases.
(e) Sterility Test- Should comply with the test for sterility described in the general monograph on ‘Viral Vaccine’.
(f) Potency Test- Four susceptible birds eight to twelve weeks old and each weighing not less than 400 g. are vaccinated by injecting subcutaneously 1 ml. of a 10-5 dilution of the product. Two weeks after vaccination these birds and four non-protected birds are challenged by injecting subcutaneously each with 1.0 ml. of a 1: 100 dilution of virulent virus (liver and spleen suspension) or 1.0 ml. of a 1 : 100 dilution of fluid from the embryo infected with virulent Ranikhet Disease virus. The non-protected birds should show symptoms of Ranikhet Disease and die and all the protected birds should remain normal during an observation period of fourteen days.
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5. Labelling- Should comply with the requirements of ‘Labelling as laid down in the general monograph on ‘Viral Vaccines’.
6. Storage- The vaccine when stored at – 15 ° C to – 20 ° C. may be expected to retain the potency for about one year and about three months if stored in a refrigerator at 2 ° C to 4 ° C. The product should not be sued if stored for more than ten days outside the refrigerator.
__________________________________________________________________ * The word “Coryza’ omitted as per G.O.I. Notification No. GSR 659(E) dt. 31-8-1994. ** Ins. as per G.O.I. Notification No. GSR 659(E) dt. 31-8-1994
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Ranikhet Disease Vaccine F strain (Living)
1. Synonyms- New castle disease vaccine F Strain (Living).
2. Definition- Ranikhet disease vaccine F. strain is a suspension of a naturally modified living virus (F strain) prepared from the infected embryos, devoid of beaks and eyes and fluids in a frozen state.
3. Preparation- Good fertile eggs obtained from salmonella pullorum free flock are incubated in an egg incubator. Eight days old vigorous embryos are infected with 0.1 ml. of 1 : 100 suspension of Ranikhet Disease vaccine F strain virus. Inoculation is done via the allantoic cavity. Embryos are incubated at 37° C. Eggs are candled every day upto four days and the dead ones are discarded. Final candling of the embryos is carried out on the fourth day and only the living ones are chilled in a refrigerator for one hour. The fluids embryos are collected separately. The fluids are tested for spot haemagglutination and sterility test is carried out. The beaks and eyes balls of the embryos are removed. The materials are homogenised with adequate quantities of antibiotics in a cool warning blender and ampouled in aliquots of 0.5 ml. quantity and freeze dried.
4. Standard - (a) Description- Light brown scales.
(b) Identification- This product affords protection to baby chicks against Ranikhet disease.
(c) Moisture content- The moisture content should not exceed *[1.0] per cent.
(d) Potency test- For testing each batch of the vaccine twelve one-day old chicks are given two drops 1/N o the field dose of the vaccine (5 ampoules selected at random may be reconstituted in 50 ml.) of cold normal saline solution. These are observed for fourteen days and the vaccinated chicks should remain normal throughout the period of observation. This serves the safety test also.
On the fourteen days the vaccinated chicks are challenged two drops with 1 : 50 virulent Ranikhet Disease virus alongwith 8 control chicks. Four of the controls receive two drops 1/N of the virulent virus while the rest of the four receive 0.5 ml. of the virulent virus. The control chicks should succumb to the challenge virus showing symptoms of Ranikhet Disease while the protected chicks should remain normal throughout the observation period of fourteen days.
(e) Sterility Test- Should comply with the tests for sterility described in the general monograph on ‘Viral Vaccine’
________________________________________________________________ *Amended as per G.O.I. Notification No. GSR 659(E) dt. 31-8-1994
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5. Labelling- Should comply with the requirements of ‘Labelling as laid down in the general monograph on ‘Viral Vaccine’.
6. Storage- The vaccine when stored at – 15 ° C to–20 ° C may be expected to retain the potency for about one year and about three months if stored in a refrigerator at 2 ° C to 4 ° C. when removed from the refrigerator, the product should not be used later than ten days.
Rinderpest Goat adapted Tissue Vaccine (Living)
1. Synonym- Goat-adapted Cattle Plague Vaccine; Goat Tissue Vaccine (Living).
2. Definition- Rinderpest Goat-adapted Tissue Vaccine is the homogenised freeze dried preparation of spleen pulp of goats artificially infected with the suitable strain of rinderpest virus.
3. Preparation- Healthy susceptible goats are quarantined for a period of ten days. After this period a batch of selected goats are injected subcutaneously with 2 ml. of a suitable dilution of the suspension of the seed virus. The donor goats are sacrificed after a suitable period when the titre of the virus in the animal body is expected to be maximum, usually four days, and the spleen from animals free from any pathological change or signs are collected under sterile conditions. Smear from each spleen is examined microscopically to exclude spleen which are contaminated from the production batch.
The spleen is freed from fat and fascia and is blended into a smooth pulp in a grinder. The pulp is spread on a shallow dish of glass or stainless steel and is freeze dried.
The freeze-dried pulp is then ground into a fine powder and sieved. The powder is ampouled in 0.25 g. or 0.125 g. quantities and freeze-dried.
4. Standard -
(a) Description- Dark brown or chocolate coloured scales or powder.
(b) Identification- The product affords protection to susceptible animals against rinderpest.
(c) Moisture content- Not more than 1.0 per cent.
(d) Safety Test- Each batch of vaccine shall be tested for safety in laboratory animals and cattle or buffalo calves as follows:-
(i) Small animals- At least two guinea pigs each weighing 300 g. to 450 g. and two adult rabbits each weighing 1 kg. to 1.5 kg. should be injected each with 1 ml. of 1: 100 suspension of the vaccine subcutaneously and kept under observation for seven days. None of the animals should die. Alternatively, a batch of six white mice each weighing not less than 18 g. may be used, each mouse receiving 0.5 ml. of a dilution 1 : 100 suspension subcutaneously. None of the animals should die.
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(ii) Large animals- Either cattle of good grade of susceptibility (hill cattle) or buffalo calves may be employed. For each batch of vaccine, three animals should be injected subcutaneously with 1 ml. of 1 : 8000 dilution of the vaccine. These animals should be kept under observation for twelve to fourteen days. None of the animals should show any untowards reactions.
(e) Sterility Test- Complies with the tests for sterility described under the general monograph in ‘ Viral Vaccine’.
(f) Potency Test- The animals receiving 1 ml. of 1 : 8000 dilution of vaccine used under safety test mentioned above and kept under observation for fourteen days, should be challenged with 1 ml. of 1 per cent suspension of stock Rinderpest Virulent virus. None of the animals should die of rinderpest within a period of ten days. This test serves as a short potency test for each of the batches.
For conducting a detailed potency test the following procedure may be followed:-
Dilution 1: 8000, 1: 12,000 and 1 : 16,000 shall be tested and for each dilution three susceptible cattle or buffalo calves should be used. Each animal is inoculated subcutaneously with 1 ml. of a dilution of the vaccine, followed twelve to fourteen days later with a standard challenge dose of virulent rinderpest bull virus containing in 1 ml. of a 1 : 100 suspension of spleen tissue. Two unvaccinated bovines, each receiving the same quantity of the challenge dose acts as controls. These are kept under observation for fourteen days. The end point of protection titre is assessed on the death or survival rate and the dose contained in one gramme of vaccine calculated on the basis of 20 to 40 minimum protective doses being equivalent to one vaccination dose.
(g) Virulence and viability Test- Two to four goats each weighing not less than 18 kg. are injected with 2 ml. of 1 : 100 suspension of the vaccine and kept under observation for ten days. These animals should show reaction characterised by pyrexia (rise of about 2° C) anorexia and dullness.
5. Labelling- Should comply with the requirement of ‘Labelling’ as laid down in the general monograph on ‘ Viral Vaccines’.
6. Storage- The vaccine may be expected to retain its potency for twelve months if stored at - 15° to 20° or about three months if stored at 2°C to 4 ° C.
Rinderpest Lapinised Vaccine (Living)
1. Synonym- Rabbit Adapted Cattle Plague Vaccine (Living) Lapinised Vaccine (Living).
2. Definition- Rinderpest Lapinised Vaccine is a suspension of a modified living virus (e.g. Nakamura III Strain) prepared with the blood spleen and mesenteric lymph glands of infected rabbits and is freeze dried.
3. Preparation- Adult rabbits possibly from a known stock, each weighing not less than 1 kg. free from cocidiosis and snuffles, are injected intravenously with 1 ml. of a suitable
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dilution of a suspension of the stock seed virus. Donor rabbits are sacrificed after a suitable period when the titre of the virus in the animals is expected to be the maximum usually the third day.
Ten millilitres of blood is collected from each rabbit in a defibrinating flask under aseptic condition. Later the animals are sacrificed and the spleen and mesenteric lymph glands collected. Each rabbit is subjected to a thorough post-mortem examination to observe lesions of rinderpest infection.
After harvesting, the blood and the organs (spleen and glands) are homogenised in a suitable proportion if necessary. Adequate quantities of penicillin and streptomycin may be added. The homogenized material is ampouled in suitable quantities and freeze dried.
4. Standard -
(a) Description- Dark chocolate coloured mass.
(b) Identification- This product affords protection to susceptible animals against rinderpest.
(c) Moisture content- Not more than 1.0 per cent.
(d) Safety Test- For testing a batch 2 guinea pigs each weighing not less than 300 g. are injected subcutaneously with 1 ml. of a 1 : 100 suspension of the vaccine. Alternatively, a group of six white mice each weighing not less than 18 g. is used. Each animal receives subcutaneously 0.5 ml. of 1 : 100 suspension of the vaccine. None of the test animals should die within a period of seven days.
(e) Sterility Test- Should comply with the tests for sterility described in the general monograph on ‘Viral Vaccines’. If antibiotics have been added the inoculum should be neutralised before doing the test.
(f) Potency Test- Dilutions 1: 100, 1 : 200, 1 : 400 and 1 : 800 shall be tested and for each dilution 2 susceptible cattle ( hill bulls) or buffalo calves should be used. Each animal is inoculated subcutaneously with 1 ml. of a dilution o the vaccine, followed twenty-one days later with a standard challenge dose of a virulent rinderpest bulls virus contained in 1 ml. of a 1 : 100 suspension of spleen tissue. Two unvaccinated bovines each receiving the same quantity of the challenge virus serve as controls. These animals are kept under observation for fourteen days. The end point of the protecting titre is assessed on the death or survival rate and the dose contained in one gramme of vaccine calculated on the basis of twenty minimum protective doses being equivalent to one vaccinating dose.
(g) Virulence and Viability Test- Four rabbits each weighing 1 to 1.5 kg. are injected subcutaneously with 1 ml. of 1 : 100 suspension of the vaccine. The animals should react typically showing all the symptoms of rinderpest in rabbits.
5. Labelling- Should comply with the requirements of ‘Labelling’ as laid down in the general monograph on ‘Viral Vaccines’.
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6. Storage- The vaccine may be expected to retain its potency for six months if stored at 15 °C to –20 °C or about a month if stored at 2 ° C to 4 °C.
Rinderpest Lapinised Avianised Vaccine (Living)
1. Synonym- Lapinised Avianised Vaccine (Living).
2. Definition- Rinderpest Lapinised Avianised Vaccine is a suspension of a modified live rinderpest virus of low virulence prepared either with the whole chick embryo or the viscera of the infected chick embryo.
3. Preparation- Twelve or thirteen days old active chick embryos from a flock free from Salmonella pullorum infection are injected intravenously with a suitable dilution of the suspension of the stock seed virus in six per cent glucose solution. The embryos are incubated at 38.5 °C for five days. At the end of this incubation period, eggs which show living embryos are selected for the preparation of the vaccine. The viscera of the chicks are harvested, care being taken to reject the gizzard and gall bladders. The material is homogenised in a blender with adequate quantities of antibiotics (penicillin and streptomycin added if necessary), and primary freeze dried done. This freeze dried material is ground into a fine powder, ampouled in suitable quantities and finally subjected to secondary freeze drying and sealed under vacuum.
4. Standard -
(a) Description- Pale cream or yellow coloured sterile powder.
(b) Identification- This product affords good grade of immunity to susceptible animals against rinderpest.
(c) Moisture content- Not more than 1.0 per cent.
(d) Safety Test- For testing each batch, a group of six mice each weighing not less than 18g. is used. Each mouse is injected subcutaneously with 0.5 ml. of 1 : 100 suspension. Alternatively, two guinea pigs each weighing not less than 300 g. and two rabbits each weighing not less than 1 kg. are injected with 1 ml. of 1 : 100 suspension subcutaneously. These animals should not show any untoward reaction during the period of observation for seven days.
(e) Sterility Test- Should comply with th e test or sterility as laid down in the general monograph on ‘Viral Vaccines’.
(f) Potency Test- Healthy highly susceptible cattle (hill bulls) or buffalo calves should be used for testing the potency of each batch of vaccine in suitable dilution. For each dilution two highly susceptible animals should be used. Each animal is inoculated subcutaneously with 1 ml. of a dilution of the vaccine, followed twenty -one to twenty -eight days after with a standard challenge dose of a virulent rindepest bull virus contained in 1 ml. of a 1 : 100
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suspension of spleen tissue. Two unvaccinated bovines, each receiving the same quantity of the challenge virus serve as controls. All these animals are kept under observation for fourteen days. The end point of protective titre is assessed on the death or survival rate and the dose contained in one gramme of vaccine calculated on the basis of forty minimum protective doses being equivalent to one vaccinating dose.
5. Labelling- Should comply with the requirements of ‘Labelling’ as laid down in the general monograph on ‘Viral Vaccines’.
6. Storage and Expiry date- The vaccine shall be expected to retain its potency for the period at temperatures as specified below:-
-15°C to – 20 °C .. Six months 2°C to 4 °C . .. One month
Sheep and Goat Pox Vaccine (Living)
1. Synonym- Sheep Pox Vaccine. Goat Pox Vaccine (Living).
2. Definition- Sheep and goat Pox Vaccine consists of the virus contained in the scabs collected from sheep artificially infected with the virus.
3. Preparation- Healthy yearling sheep are infected artificially on the shaved portion of the abdomen with a suitable dilution of the suspension of the stock seed virus 50 per cent glycerine saline solution. The material from the semi-dried areas where the pock les ions are evident is collected and dried over calcium chloride or phophorus pentoxide under vacuum. Dry scabs are powdered, sieved, ampouled in suitable quantities and sealed.
4. Standard -
(a) Description- Light cream coloured powder.
(f) Identification- This product when applied to scarified area of the skin of the sheep or goats produces characteristic local lesions of pox and should afford protection to sheep and goat against Sheep and Goat Pox.
(g) Safety Test- Two rabbits each weighing not less than 1 kg. are injected subcutaneously each with 1 ml. of a 1 : 100 dilution of the vaccine in normal saline solution. These animals are observed for fourteen days. The animals should remain normal.
(h) Sterility Test- Complies with the tests for sterility described under the general monograph on ‘Viral Vaccines’.
(i) Potency Test- Four yearling sheep are inoculated with 1 : 100 suspension of the vaccine in 50 per cent glycerine saline on a scarified area on the
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abdomen. Fourteen days later, these and two more susceptible sheep are inoculated by the same method with stock virus and observed for a period of fourteen days. The control animals should develop typical lesions of pox and vaccinated animals should remain normal.
5. Labelling- Should comply with requirement of ‘Labelling’ as laid down in the general monograph on ‘Viral Vaccines’.
6. Storage and Expiry date- The vaccine shall be expected to retain its potency for period at temperatures as specified below:-
-15 °C to – 20 °C .. . . .Twenty months 2°C to 4 °C . .. . . Three months Room Temperature .. . . Fifteen days.
Fowl Spirochaetosis Vaccine ( Chick Embryo Origin)
1. Synonym- Tick Fever Vaccine.
2. Definition- The vaccine consists of a merthiolated suspension of chorioallantoic membrane, internal viscera and blood of chick embryos infected with a vaccine strain of spirochaetes and freeze dried.
3. Preparation- Eleven days old developing chick embryos are infected with 0.2 ml. of sterile fresh blood containing spirochaetosis via the chorioallantoic membrane. The inoculated embryos are incubated at 37 °C and candled daily and the dead one are discarded. On the seventh day the living embryos are chilled in the refrigerator for two hours. The chilled embryos are harvested separately and necrotic lesions in liver noted. Representative samples of blood should be examined for teaming spirochaetes. The internal viscera, chorio- allantoic memranes and the blood are collected. The material is pooled, weighed and held in deep freeze at – 15 °C to –20 °C for a period of one week. Thereafter the material is blended with equal quantity of Merthiolate (final concentration of merthiolate in the suspension should be 1 : 10, 000) thoroughly for three times, each time the motor running at full speed and the vaccine is ampouled in 2 ml. quantities and freeze dried.
4. Standard -
(a) Description- Light brownish scales.
(b) Identification- The vaccine affords protection when inoculated into the fowls against spirochetosis .
(c) Moisture content- The moisture content should not exceed 1.0 per cent.
(d) Safety and potency test- Six healthy cockerals ten to twelve weeks old are used for this purpose. Each ampoule of vaccine is reconstituted in 10 ml. of cold distilled water and the six
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cockerals are injected intramuscularly each with 1 ml. of the reconstituted vaccine and the birds are observed for a period of ten days and the vaccinated birds should remain normal throughout the period of observation. The vaccinated birds are challenged with 0.2 ml. intramuscularly with virulent spirochaete blood along with two susceptible controls. Temperature and blood smear examination of the challenged birds and controls should be carried out daily for a period of ten days. The blood smears of vaccinated birds should remain negative for spirochaetes during the entire period of observation. The controls should react and show spirochaetes in the blood.
(e) Sterility Test- Complies with the tests for sterility described in the general monograph on ‘ Bacterial Vaccine’.
5. Labelling- Should comply with requirement of ‘Labelling’ as laid down in the general monograph on ‘Viral Vaccines’.
6. Storage- The vaccine when stored at –15 °C to – 20 °C may be expected to retain the potency for about one year and about two months if stored in refrigerator at 2 °C to 4 °C.
Swine Fever Vaccine Crystal Violet
1. Synonym- Crystal Violet Swine fever vaccine, Hog Cholera Vaccine.
2. Definition- Swine fever vaccine, crystal violet is a suspension of blood of swine that have been infected with a suitable virulent antigenic strain of swine fever virus, inactivated with 0.25 per cent crystal violet ethylene glycol at 37 °C for fourteen days.
3. Preparation- Susceptible healthy pigs of six to seen months of age belonging to a well established strain or bred are used. Body weight of these animals at this age may vary according to the breed nut optimum weight is considered as between 75 to 100 kg. Animals used for production may be procured from well established farms and kept under quarantine or fourteen days. These are injected intramuscularly with a suitable dilution of the suspension of the virulent blood viruses. Bleed ing of the clinically injected animals is carried out on the sixth day. The defibrinated blood from each animal is strained and stored separately in sterile glass containers. To the four parts of defibrinated blood, one part of 0.25 per cent crystal violet- ethylene glycol is added and the suspension after thorough mixing, is stored at 37 °C ( 0.5) for two weeks. The product is filled ill 20 ml. volumes in sterile vials and labelled on the completion o tests.
4. Standard -
(a) Description- Very dark violet suspension.
(b) Identification- This product affords protection against swine fever but not against African Swine Fever.
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(c) Safety Test- Two young pigs weighing about 15 to 30 kg. are injected subcutaneously each with 40 ml. of the vaccine batch to be tested. In addition, one unvaccinated susceptible pig is placed in contact.
(d) Sterility Test- Should comply with the test for sterility described under general monograph on ‘Viral Vaccines’.
(e) Abnormal toxicity test- Two guinea pigs are given 1 ml. or vaccine intramuscularly.
Two guinea pigs are given 2 ml. of the vaccine intraperitoneally. Two mice are given 0.5 ml. of he vaccine subcutaneously.
(f) Potency Test- Four susceptible pigs weighing between 20-30 kg. are injected with 5 ml. of the vaccine subcutaneously. After twenty-one days these are challenged with 1 ml. of suitable dilution o the challenge virus subcutaneously. The dose must contain at least 1000 minimum infective doses. At least two control pigs should be used.
5. Labelling- - Should comply with requirement of ‘Labelling’ as laid down in the general monograph on ‘Viral Vaccines’.
6. Storage- The vaccine may be expected to retain its potency for twelve months if stored in refrigerator at 2 °C to 4 °C.
Swine Fever Vaccine Lapinised (Living)
1. Synonym- Lapinised swine fever vaccine, freeze dried lapinised swine fever vaccine.
2. Definition- Swine fever lapinised vaccine consists of the suspension of a modified live swine fever virus prepared from spleens of infected rabbits and is freeze dried.
3. Preparation- Healthy adult rabbits weighing approximately 1000 gms. Or over, free from coccidiosis snuffles etc. are injected intravenously with a suitable dose of a dilution of the modified rabbit adapted virus. Rabbits are sacrificed at the height of reaction and spleens are collected with sterile precautions. The collection is later homogenised in a blender using ten per cent yolk phosphate buffer as a diluent. The suspension is ampouled in 0.5 ml. quantities and freeze dried.
4. Standard -
(a) Description- Light scales.
(b) Identification- This product affords protection against swine fever.
(c) Moisture content- The moisture content should not exceed 1.0 per cent.
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(d) Safety Test- Six mice are injected each with 0.5 ml. of a 1 : 100 suspension of the vaccine. These are kept under observation for seven days. Non should die.
(e) Viability Test- Two healthy rabbits are injected intramuscularly with 1 ml. of 1 : 100 suspension o the vaccine. These animals show thermal reaction. Sterility Test- Should comply with the test for sterility described under the general monograph on ‘Viral Vaccines’.
(f) Potency Test- The vaccine batch under test should be tested on susceptible healthy pigs weighing between 20-30 kg. Two animals for each dilution may be used. The dilutions tested are 1 : 10, 1 : 25, 1 : 50 and 1 : 100. One millilitre of each off these dilutions is injected subcutaneously. One healthy, susceptible, unvaccinated in contact animal should be kept along with the vaccinated animals.
Fourteen to twenty-one days later these animals along with two controls are injected subcutaneously with 1 ml. of the challenge virus containing at least 1000 minimum infective doses.
5. Labelling- Should comply with requirements of ‘Labelling’ as laid down in the general monograph on ‘Viral Vaccines’.
6. Storage- The vaccine may be expected to retain its potency for six months if stored at temperature ranging between – 10 °C to - 15°C and for seven days at 2 °C to 4 °C in the refrigerator.
*[Foot and Mouth Disease Vaccine (Inactivated)
1. Synonym. – Inactivated Tissue culture mono or polyvalent Foot and Mouth Disease Vaccine.
2. Definition. – Foot and Mouth Disease Vaccine is a liquid product or preparation containing one or more types of foot and mouth disease virus which have been inactivated in such a way that its immunogenic property is maintained. It may also contain an adjuvant. The vaccine is described as monovalent, bivalent, trivalent or polyvalent depending on the number of types of virus used.
________________________________________________________________________ *Ins. As per G.O.I. Notification GSR No.659(E) dt. 31-8-1994.
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3. Preparation. – The virus is propagated in suitable cell culture. The cell culture is infected with an appropriate inoculum of virus and incubated at a suitable temperature for multiplication of virus. The virus is harvested and cellular debris removed by filteration. Inactivation is carried out by a suitable agent such a formaldehyde solution or aziridine compound. The adjuvant may be aluminium hydroxide and/or saponin. In case of inactivated gel vaccine the antigen is concentrated by sedimentation at plus 4 degree C. for preparing a polyvalent vaccine, monovalent antigens are mixed in appropriate quantities to give the final mixture which is the formulated vaccine.
4. Standards :
(a) Description :- Aluminium hydroxide gel vaccines settle down to variable degree on storage leaving the supernatant clear.
(b) Identification – It protects cattle against Foot and Mouth Disease due to homologous type/subtype of virus.
(c) Sterility test – It shall comply with the tests for sterility as prescribed under the “general monograph of viral vaccines”.
(d) Safety test - The test is carried out on fully susceptible cattle not less than 12 months of age and which have not been sensitized either by vaccination or previous infection. Inoculate 3 susceptible cattles each with 2 ml. of finished product at multiple sites on tongue by intradermal route and observe for 4 days. The same animals are inoculated on 4th day with 3 cattle doses subcutaneously and are observed for a further period of 6 days. The animals should not develop any signs of FMD and remain normal.
(e) Potency test – Each batch of the vaccine is to be tested in susceptible cattle of not less than 15 months of age. The potency test in cattle can be done either by :-
(i) PD50 method :- The vaccine shall be tested by the determination of PD50 in susceptible cattle by challenging animals vaccinated with appropriate dilution of the vaccine made in adjuvanted or non- adjuvanted diluent as appropriate.
A minimum of 5 animals should be used per dilution and 2 unvaccinated animals to be included as controls to the challenge. All animals are needle challenged with 10,000 ID50 of the homologous strain of virus by inoculation on the tongue on the 21st day of post- vacination.
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The control animals are to be similarly challenged. Animals are observed for 10 days for the development of lesions. Unprotected animals show generalized lesions due to FMD. Control animals must shown generalized lesions. From the number of animals protected in each group the PD50 content of the vaccine is calculated. The vaccine passes the test if an observed PD50 value of 3 or greater is obtained in the test.
(ii) Percentage protection method in which groups of ten health susceptible cattle are each injected subcutaneously with the vaccinating dose and 14 – 21 days later the cattle are challenged by intradermal injection into three separate sites on the tongue with 10,000 ID50 of the strain of virus used in the preparation of the vaccine. The vaccine can be passed if atleast seven out of the ten in the group are protected against the development of generalized infection whereas all the controls should react by developing primary and secondary lesions observable in the mouth and feet.
For other reasons if cattle testing is not possible then the potency of the vaccine may be assed in guineapigs either by Lucam ‘C’ index or PD50 method by challenging those which have been previously vaccinated, provided that the correlation has been established between guineapig challenge test and cattle challenge results.
The estimation of the serum neutralizing antibody titre cattle may be considered as a supportive test to evaluate potency of vaccine.
However, potency testing of vaccines, in cattle, of batches whenever by other accepted methods of testing is in doubt, at aleast one out of every five batches, be undertaken.
5. Labelling :- It is labeled as described under the requirements of ‘labelling’ as laid down in the general monograph, with the additional requirements that the label on the container states the virus types used in the preparation.
6. Storage :- It should be protected from the light and stored between 4oC to 8oC. under these conditions it may be expected t retain its potency for not less than 12 months. Freezing of aluminium hydroxide vaccine must be avoided. The frozen product will not be fit for use.
Canine Hepatitis Vaccine (Living)
1. Synonyms :- Infectious Canine Hepatitis Vaccine (Living), Canine Hepatitis Cell Culture Vaccine.
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2. Definition :- Canine Hepatitis Vaccine (Living) is a freeze dried preparation of tissue culture fluid containing the cell culture adopted canine hepatitis virus.
3. Preparation :- Canine hepatitis vaccine shall be prepared from virus bearing cell culture fluid.
Only stock seed virus which has been established as pure, safe and immunogenic shall be used in the preparation of the vaccine.
4. Immunogenicity test :- Each lot of stock seed virus shall be tested for immunogenicity as follows :-
Thirteen canine hepatitis susceptible dogs, 8-14 weeks old shall be used for the test (10 vaccinates and 3 controls). Blood samples may be drawn from these animals and individual serum samples tested for the presence of antibodies, against canine hepatitis virus. Ten dogs shall be injected subcutaneously with predetermined quantity of the virus and remaining 3 dogs are kept as unvaccinated controls. The dose calculation will be based on virus titration in suitable cell culture system. Not less than 14 days post vaccination, the vaccinated and control shall each be challenged intravenously with virulent infectious canine hepatitis virus and observed daily for 14 days. At least 2 out of 3 controls should die and the survivors shall show the clinical signs of canine hepatitis. Nine out of ten vaccinated dogs shall survive and shall not show any signs of infectious canine hepatitis during the observation period.
The stock seed virus shall be tested once in 5 years and maintained under standard conditions as prescribed.
The stock seed virus may be inoculated on a suitable tissue culture system and may be incubated for five to seven days.
The tissue culture fluid is then harvested and titrated in cell culture system for virus content. After appropriate dilution and pooling, the material is stored at minus 20 oC until freeze dried. Each vaccine dose shall contain not less than 103.5 TCID50 dose,
4. Standards :-
(a) Description. – The dried product is a pinkish cream material readily dispersible in water. The reconstituted vaccine is a pinkish liquid.
(b) Identification.- It causes characteristic cytopathic effect in dog, pig and ferret kidney monolayers. This can be neutralized by specific antiserum. When inoculated into dogs, the development of specific neutralizing antibodies can be demonstrated by suitable serological tests.
(c) Moisture content.- In the finished product moisture content shall not exceed 1.0 per cent.
(d) Sterility Test.-- Shall comply with the tests of sterility as described under
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the general monograph on “Viral Vaccines”.
(e) Safety Test.-- Mouse safety test – Vaccine prepared for use as recommended on the label shall be tested. Eight mice shall be inoculated intracerebrally with 0.03 ml and 8 mice shall be inoculated intraperitoneally with 0.5ml. both the groups shall be observed for seven days. If unfavourable reaction attributable to the product occurs in two or more mice in either group during their observation period, the batch is unsatisfactory.
Dog Safety Test. -- Each of the two susceptible pups aged 8 – 14 weeks shall be injected with vaccine equivalent of 10 vaccinating doses from the batch reconstituted with sterile diluent and administered in the manner recommended on the label and observed for 21 days. None of the pups shall show any unfavourable reaction during the period of observation.
(f) Potency test, Virus Titration :- Samples of finished product shall be tested for virus titre in suitable cell culture system. The batch shall have a virus titre of not less than 10 3,5 TCID50 dose.
Potency test in dog.- : Two healthy susceptible dogs of 8-14 weeks of age shall be injected subcutaneously with one Vaccine dose. 14 days after vaccination, specific neutralizing antibodies from both the dogs shall be demonstrable by serological tests.
5. Labelling.-- Shall comply with the requirement for labeling as laid down in the general monograph on “Viral Vaccines
6. Storage.-- The dry product shall be stored at temperature of minus 20oC or below. The vaccine is expected to retain its potency for about 6 months in the freezing chamber of the refrigerator (temperature) approximately minus 8oC
Duck Plague Vaccine
1. Definition.- Duck plague vaccine is a suspension of modified living virus prepared from infected chick embryos.
2. Preparation.- Fresh fertile hen’s eggs obtained from Salmonella free flocks are incubated in an incubator. None days old embryos are injected with 0.2ml of the suitable dilution ( 1 in 100) of the suspension of the virus on the CAM and incubated at 37oC for 5 days post-inoculation. Dead embryos of the 3rd, 4th and 5th days post-inoculation are harvested. The embryos (devoid of head and legs). Clear fluid and the membranes are collected and homogenized in a Blender, ampoulded in 0.5ml quantities and freeze dried.
3. Standards:-
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(a) Description.- Light brown scales.
(b) Identification.- This product affords protection to the ducks against duck plague.
(c) Safety Test. - Four healthy, 8 to 12 weeks old ducks weighting not less than 600 grms are inoculated subcutaneously with 1ml of 10-1 dilution of the vaccine and observed for a period of 14 days. During the period of observation, the ducks shall not show any untoward reaction.
(d) Sterility.- Shall comply with the test for sterility described in the general monograph on “Viral Vaccines”.
(e) Potency Test. - Six susceptible ducks 8 to 12 weeks old each weighing not less than 600 gms are inoculated subcutaneously with 1 ml of 10-3 dilution of the vaccine. The minimum virus contents in 1 ml. dose of the vaccine shall be 103.5 EID50. 14 days later these ducks are challenged subcutaneously each with 1ml. of 10-2 dilution of the virulent duck plague virus (1000 DEID50) along with 2 unprotected young ducks of about 8-12 weeks age. The unprotected ducks shall show symptoms of duck plague and die within 10 days, while the protected ducks shall remain normal during the observation period of 14 days.
4. Labelling.- Should comply with the requirements of labeling as laid down in the general monograph on “Viral Vaccine”.
5. Storage.- Vaccine when stores at minus 15oC to minus 20oC may be expected to retain its potency for one year and about three months if stored in the freezing chamber of Refrigerator i.e. minus 5oC.
Avian Encephalomyelitis Vaccine (Living)
1. Synonyms.- Avin encephalomyelitis Vaccine Freeze dried.
2. Definition.- A virus bearing tissue and fluid suspension from embryonated hen’s legs.
3. Preparation.- The stock seed virus which has been established as pure, safe and immunogenic shall be used for preparing the vaccine.
(i) Each lot of stock seed virus shall be tested for pathogenicity by chicken embryo inoculation test:
(a) One dose of the seed lot shall be mixed with 9 volume of sterile heat inactivated specific, antiserum to neutralize vaccine virus in the product.
(b) After neutralization, 0.2ml of serum vaccine mixture shall be inoculated into
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each of at least 20 fully susceptible chicken embryos (0.1ml of the inoculum shall be inoculated on CAM of 9-11 days old embryos and 0.1 ml in the allantoic sac).
(c) Eggs shall be candled for 7 days. Deaths occurring during first 24 hours shall be discarded but at least 18 viable embryos shall survive 24 hours post inoculation for a valid test. All embryos and CAMs from embryos which die after the first day shall be examined.
(d) If the death or abnormality attributable to inoculums occur, the seed lot is unsatisfactory.
(ii) Immunogenicity test.- Avin encephalomyelitis susceptible chicks, all of same age (8 weeks old) shall be used 20 chickens shall be inoculated with the field dose of the virus by prescribed route. Ten additional chickens of same age and flock shall be held as unvaccinated controls.
At least 21 days post vaccination, the controls and vaccinates shall be challenged intracerebrally with Virulent avian encephalomyelitis virus and observed each for 21 days. At least 80 percent of controls shall show signs of avian encephalomyelitis or die. At least 19 to 20 vaccinates shall remain free from clinical avian encephalomyelitis during the observation period for the stock seed virus to be satisfactory.
4. Standards:- (a) Description:- Greyish white flakes easily dispersible in the diluent.
(b) Identification :- At least 5–6 days old embryonated eggs (from hens with no history of infection with avian encephalomyelitis) shall be inoculated with 0.1 ml of undiluted vaccine into the yolk sac and kept in incubator and then transferred to the brooder where they are allowed to hatch. The hatched chicks shall be raised for 7 days. More than 5 per cent of hatched chicks shall manifest the typical symptoms (weak-led, leg paralysis tremor etc.) at the end of this period.
(c) Moisture Content: - Shall not exceed 1.0 per cent.
(d) Sterility Test: - Shall comply with the test for sterility described under general monograph on “Viral Vaccines”.
(e) Safety Test: - At least 25 avian encephalomyelitis susceptible birds (6-10 weeks of age) shall be vaccinated with 10 field doses by the recommended route and observed each day for 21 days. If unfavourable reactions attributable to the vaccine occur during the observation period, the batch of vaccine is unsatisfactory.
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(f) Potency Test: - (i) The vaccine shall be titrated for virus content. To be eligible for release,
the batch shall have a virus titre of at least 10 2.5 EID50 per dose.
(ii) At least 10 susceptible chickens shall be vaccinated with the field dose of the vaccine by prescribed route and 10 chickens from same batch and source shall be kept as unvaccinated controls.
At least 21 days post-vaccination, both the groups shall be challenged intracerebrally with Virulent avian encephalomyelitis virus and observed for 21 days. At least 8 out of 10 controls shall develop recognizable signs or lesions of avian encephalomyelitis and at least 8 out of 10 vaccines should remain normal
5.Labelling Shall comply with the requirement of labeling as laid down in general monograph on “Viral Vaccines”.
Marek’s Disease Vaccine (Living)
1. Synonyms.- Herpes virus of Turkey Vaccine HVT vaccine (Living).
2. Definition:- Marek’s disease vaccine is a suspension of cell free fluid containing live virus.
3. Preparation.- The stock seed virus which has been established as pure, safe and immunogenic in avian species shall be used for preparing the seed virus for vaccine production.
(i) Safety Test – The stock seed virus shall be non-pathogenic for chickens as determined by the following procedure:
The groups of at least 25 chickens each at one day of age shall be used. These chickens shall be of the same source and batch be susceptible to Marek’s disease and be kept in isolated group.
Group 1: Each chicken shall be injected with 0.2ml of 10 times as much viable virus as will be contained in one dose of vaccine by intramuscular route.
Group II : Shall be serve as controls. At least 20 chickens in each group shall survive for four days post injection. All chickens that die shall be necropsied and examined for lesions of Marek’s disease and cause of death. The test shall
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be judged according to the following :
At 120 days o age, the remaining chicken in both the groups shall be weighted, killed and necropoised. If at least 15 chicken in each of these two groups have not survived the 120 days period if any of the chicken of group-I have gross lesions of Marek’s disease at necroposy or if the average body weight of the chickens in Group-I is significantly (statistically) differen t from the average of Group-II at the end of 120 days, the lot of stock seed virus is unsatisfactory.
(ii)
(iii)
Purity test – Shall be conducted in chickens and no lesions other than those typical of Turkey Herpes virus shall be evidenced.
Immunologenicity test – Sixty susceptible day old chicks are used. Thirty of them inoculated with the seed virus in a dose corresponding to the field dose of the final vaccine and 14-21 days later challenged by intrabdominal route with virulent Marek’s diseas virus, alongwith the other 30 non-vaccinated control chicks. At the end of the observation period when the chicks are 20 weeks old, the surviving chickens are examined for the presence of antibody against Marek’s disease by serological tests and postmortem inspection for lesions of Marek’s disease.
Any bird dead is thoroughly examined and the cause of death ascertained by necropsy/histopathological examination. All the surviving birds are killed and necropsied. The protection index (P1) is determined by following procedure :
No. with MD lesions 1. Percent MD = _________________________ x 100
No. with MD lesions + No. of –ve Su-viviours (effective No.)
Percent MD in controls – Percent MD in vaccinated
2. P.I. = _______________________________ x 100 Percent MD controls
Master seed virus should have P.1 of at least 80 per cent.
Eighty per cent of the chicks in the control group must fall ill specifically. If more than 80 per cent of the vaccinated chickens do not show symptoms or signs of Marek’s disease, the seed virus is regarded as sufficiently effective and can be used for production of vaccine.
The seed virus is propagated in duck embryo fibro-blast cell culture, chick embryo fibroblast or any other suitable cell culture (specific pathogen free SPF flock) and when the peak passage level is attained the cell monolayer is suspended in cold diluent of the following composition.
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SPGA Stablizer 0.218% Sucrose 0.0038% mono sodium phosphate 0.0072% dipotassium phosphate L Monosodium glutanate 0.0049 M 1 per cent bovine albumin Fraction (V)
0.25 per cent EDTA (Sterilised by Seitz filteration and stored at minus 10oC). The virus is freed from cell by ultrasonication for 3 minutes interrupted after every 30 seconds) at 100 MA and freeze dried in convenient volumes. The doses per ampoule vial is calculated after titrating the freeze dried product in terms of plaque forming units (PFU) in the corresponding cell monolayers.
4. Standards:-
(a) Description: - The cell free freeze dried HVT vaccine look uniformly grayish in colour and easily dispersible in the specified diluent.
(b) Identification. - The vaccine on inoculation in suitable cell culture system shall cause cytopathi effect typical of Herpes virus of Turkey. Specific antiserum of Herpes vifus of Turkey shall neutralize the cytopathic effect.
(c) Moisture content. - Moisture content shall not exceed one per cent.
(d) Sterility test. - Shall comply with the test prescribed in general monograph on “Viral Vaccines”.
(e) Safety Test.- At least 25 one day old chickens shall be injected with ten times of the field dose of vaccine by intramuscular route. The chickens shall be observed each day for 21 days. Chickens dying during the period shall be examined. Cause of death determined and the results recovered as follows :-
(i) If at least 20 chickens do not survive the observation period, the test is in conclusive.
(ii) If lesions of any disease or cause of death are directly attributable to the vaccine the vaccine is unsatisfactory.
(f) Potency test. - The sample shall be titrated in the cell culture system. A satisfactory batch shall contain at least 1500 plaque forming units (PFU) as per dose at the time of release and maintain at least 1000 PFU till the end of expiry period.
5. Labelling. - Shall comply with the requirements of labeling as laid down in general monograph on “Viral Vaccines”.
6. Storage and expiry date. - The freeze-dried cell free HVT vaccine may be stored at o
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4oC for 6 months.
Goat Pox Vaccine (Living Cell Culture)
1. Synonym. - Goat Pox Vaccine (living), attenuated goat pox vaccine.
2. Definition. - Goat Pox vaccine is freeze-dried preparation, prepared by growing attenuated goat pox virus in kid kidney/testicular cell culture.
3. Preparation. - Primary kidney/testicular cell Cultures of disease free kid are used. The monolayers infected with the seed virus are incubated at 37oC. The cultures are harvested by three cycles of freezing and thawings 6 to 7 days post infection when
4. Standards: -
(a) Description. - Light yellow colour
(b) Identification - The product affords protection to goat against goat pox.
(c) Moisture content. - The moisture content shall not exceed 1.0 per cent.
(d) Safety test.-
(i) Laboratory animals. - Six mice, 3 guinea pigs and 3 rabbits are inoculated with 0.2ml intraperitoneally, 0.5ml and 1.0 ml subcutaneously, with 10 field doses of the vaccine. The inoculated animals during the observation period of 80 days shall remain normal.
(ii) Goat. - Two susceptible goats of 6 to 8 months of age are inoculated in postaxillary region by subcutaneous route with one-hundred field dose of the vaccine. The inoculated animals shall not develop more than a local reaction of 2 to 3 cms. These animals shall be observed for 10 days.
(e) Sterility test. - Shall comply with the test for sterility described under the general monograph on “Viral Vaccines”.
(f) Titration in cell culture.- Four randomly selected samples are inoculated in kid kidney cell cultures using 5 tubes for each dilution. The titration shall be repeated thrice. One thousands TCID 50 is used as a field dose.
(g) Potency Test.- The three susceptible goats (8-10 months) are inoculated with 1/10th field dose and 3 susceptible goats (8-10 months) with one filed dose, subcutaneously. Three incontract controls are also kept with the inoculated goats. These animals are observed for a period of 14 days and their body temperature recorded daily. The vaccinated animals shall not show any termal, local or
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generalized reaction. Twenty one days post infection, the vaccinated and controls and challenged with 10,000 TCID50 of virulent goat pox virus by intradermal route. The temperature of these goats are recorded for a period of 14 days. The vaccinated goats shall not develop localized or generalized reaction while control goats shall develop high fever, localized reaction or even generalized reaction in some cases.
5. Labelling .- Shall comply with requirements of labeling as laid down in the general monograph on “Viral Vaccines”.
6. Storage and expiry date. - The vaccine is expected to retain its potency for 12 months if stored at minus 15 oC to minus 20oC and for three months at 2 to 4oC.
Sheep Pox Vaccine (Inactivated)
1. Synonym .- Formal gel sheep pox vaccine.
2. Definition .- Sheep pox vaccine is a formaline inactivated gel treated tissue vaccine.
3. Preparation.- Healthy susceptible sheep of 8-12 months of age are inoculated subcutaneously with 500ml of the 1:100 dilution of the Russian Virulent Sheep Pox Virus. Seven to eight day post inoculation skin of the abdomen alongwith the oedema is collected. The infected tissues are homogenized in 10 percent concentration in phosphate buffer (ph 7.4-7.6) which after the extraction of the virus is mixed with sterile gel and buffer in the following proportion :-
6 percent aluminium hydroxide gel-50 per cent. Phosphate Buffer (pH 7.6)- 35 per cent. 10 per cent suspension – 15 per cent
This is later formalized and kept at 20-25oC/10oC for varying periods.
4. Standards.-
(a) Description .- It is a grayish white suspension. During storage the gel settles at the bottom, upper layer of the suspension is clear.
(b) Identification.- This product affords protection to sheep against sheep pox.
(c) Safety test. - This is carried out by inoculating 2 white mice with 0,2ml one guinea pig with 1.0 ml and one rabbit with 3,0 ml of vaccine. The animals should remain clinically healthy for 10 days.
(d) Sterility test.- This is done by seeding the vaccine on usual bacterial media. The plates and tubes are incubated for 10 days at 37 oC. If the pathogenic bacteria are
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found, the vaccine is rejected while with non-pathogenic bacteria the vaccine is passed for field use.
(e) Potency test.- This is done by inoculating 4 non immune susceptible sheep preferably exotic breed of 1-2 years with 3 ml of vaccine in the thigh, subcutaneously.
The vaccinated sheep are challenged 15 days after inoculation alongwith 3 controls each with 0.1 ml of virulent virus containing 200 infective doses intradermally under the tail. The sheep are observed for 10 days and their skin reaction recorded. The vaccine is considered potent if at all the vaccinated, sheep do not show thermal or local skin reaction. Vaccine is also potent if 3 vaccinated animals do not develop any reaction and one shows abortive skin reaction, while at least 2 of the 3 controls develop typical sheep pox reaction at the site of inoculation.
5. Labelling.- Shall comply with the requirements of labelling as laid down in the general monograph on “ Viral Vaccines”.
6. Storage.- The vaccine shall be stored at 4 to 5oC. it keeps well at above temperature upto 12 months.
Sheep Pox Vaccine (Living Cell Culture)
1. Synonym.- Sheep pox vaccine (Living), attenuated sheep pox vaccine.
2. Definition.- Sheep pox vaccine is freeze dried preparation prepared by growing attenuated sheep pox virus in lamb kidney/testicular cell cultures
3. Preparation.- Primary cell cultures prepared from kidney/testicles of disease free lambs are used. The mono layers infected with the seed virus are incubated at 37oC. the cultures are harvested by 3 cycles of freezing and thawing 6 to 7 days post infection when more than 80 per cent Cells show C.P.E. the suspension is centrifuged at 1000 r.p.m. for 10 minutes to remove cellular debris before being stored at minus 20oC. the suspension is freeze dried after addition of 5 per cent Lactalbumin hydrolysate and 10 per cent sucrose.
4. Standards:-
(a) Description.- Light yellow colour.
(b) Identification.- The product affords protection to sheep against sheep pox.
(c) Moisture contents.- The moisture contents should not exceed 1.00 per cent.
(d) Safety tests.-
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(i) Six mice, 3 guinea pig and 3 rabbits are inoculated with 0.2ml intraperitoneally 0.5ml and 1.0 ml subeutaneously, respectively containing 10 field dose of the vaccine. The inoculated animals during the observation period of 10 days should remain normal.
(ii) One hundred field doses of the vaccine are inoculated subcutaneously into each of 3 susceptibles sheep in postaxillary region. Inoculated animals shall not develop more than a local reaction of 2 to 3 cms.
(e) Sterility test. - Shall comply with the test for sterility as described under the general monograph on “Viral Vaccines
(f) Titration in cell culture. - Four randomly selected samples reconstituted in a maintenance medium are inoculated in lamb kidney cell cultures using 5 tubes for each dilution. The titrations shall be repeated thrice. The TCID50 to be calculated by Read and Muonch method. One thousand TCID50 is calculated as one field dose.
(g) Potency test. - Three susceptible sheep 8-10 months old are inoculated with 1/10th, field dose and 3 susceptible sheep with one field dose, subcutaneously. Three in contact controls are also kept with the inoculated sheep. These animals are observed for a period of 14 days and their temperature is recorded daily. The vaccinated animals should not show any thermal, local or generalize reactions. Twenty one days post infection the vaccinated and controls and challenged with 10,000 ID50 of virulent sheep poxvirus by intradermal route. The temperature of these sheep are recorded for a period of 14 days. The vaccinated sheep should not develop localised or generalized reaction while control sheep should develop high fever, localized reaction or even generalized reaction in some cases.
5. Labelling.- Shall comply with requirements of labelling as laid down in the general monograph on “viral vaccines”.
6. Store and expiry date.- The vaccine is expected to retain its potency for 12 months if stored at minus 15oC to 4o.
Tissue Culture Rinderpest Vaccine
1. Synonym.- Cell culture Rinderpest Vaccine.
2. Definition.- These culture Rinderpest vaccine is a freeze dried preparation of live modified rinderpest virus adapted to any propagated in cell culture.
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3. Preparations.- Primary or secondary monolayer cultures of the kidney cells (Bovine or any other suitable animals) taken from kidney from healthy animals free from any pathological changes shall be used. When secondary cultu5es are used they shall have retained their original morphology and Karyo type. Kabeto ‘O’ stain of Rinderpest virus developed by East African veterinary Research Organisation (Plowrights strain between the passage levels of 99th and 100th passages) shall be used. The virus harvested from cell monolayer culture prepared from the kidneys of a single calf or serially cultivated bovine kidneys cells (Not more than 10 passages away from the Primary) inoculated with the same seed and harvested together, will be freeze dried with stabilizers in suitable quantities.
4. Standards.- It complies with the requirements of general standards of viral vaccines:
(a) Description.- Dry light yellow coloured flakes readily soluble in chilled and saline or buffered saline.
(b) Identifications.-
(i) Protects cattle against a subsequent challenge with virulent or caprinised rinderpest virus.
(ii) It is titrable in tissue culture systems capable of supporting the multiplication of this virus. These shall be made on at least three separate occasions using a cell culture derived from different animals.
(iii) Specificity test shall be performed using an appropriate scrum neutralization test.
(c) Sterility test. - Each batch shall be tested for bacterial and mycotic sterility as given in general monograph on “Viral Vaccines”.
(d) Innocuity test.- Shall be made on each batch in at least two guinea pigs and six mice. These animals shall be observed for atleast two weeks fro any untoward reaction.
(e) Safety and efficacy test. - The test for safety and efficacy shall be performed using the pooled reconstituted contents of not less than 4 ampoules taken at random. The vaccine shall be injected subcutaneously into each of at least two susceptible cattle free from specific antibodies using the quantity containing not less than 100 fields doses and two further cattle and using 1/10th of the field dose (calculated on the basis of 1000 TCID50 one field dose). The animals shall be housed with a least two unvaccinated animals and observed for a period of three weeks. The vaccine passes the safety test if the cattle show no signs of unusual clinical reactions.
At the end of three weeks all the four animals will be challenged alongwith two incontact cattle with a challenge dose of not less than 10th ACID50 of virulent Rinderpest virus. The
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vaccine passes the potency/efficacy test if the in contact animals develop rinderpest and all the vaccinated animals remain normal.
6. Labelling.- Shall comply with general monograph on “Viral Vaccines”. Each ampoule or at least 50 percent ampoules in a lot shall contain at least following print :
(i) TCRP Volume (ii) Batch No. with year (iii) General instructions for use.
7. Storage .- The vaccine when stored at minus 20oC and plus 4 degree C will maintain its titre for 2 years and 6 months respectively.
Canine Distemper Vaccine
1. Synonyms.- Cannine distemper Vaccine (Living)- Freeze-dried.
2. Definition.- It is freeze dried preparation of either tissues from chick embryo containing eggs adapted strain of cannine distemper virus or the cell culture in which modif ied virus has been cultivated.
3. Preparation.- Canine distemper vaccine shall be prepared from virus bearing cell culture, fluid or infected chroioalantoic membrane. Only stock seed virus which has been established as pure, safe and immunogenic shall be used for preparation of vaccine. Stock seed virus propagated in chicken embryo shall be tested for pathogen by chicken embryo test. One volume of the virus shall be mixed with 9 volume of specific sterile heat inactivated serum to neutralize the virus. Mixture shall be inoculated into twenty (9 to 11 days old ) chicken embryo (with 0.1 ml on CAM and 0.1 ml in alantoic sac). Embryonated eggs shall be candled for 7 days daily. Death occurring in the first 24 hours shall be discarded. CAMS of embryos which dieafter 24 hours shall be examined. When necessary embryo sub-culture shall be made to determine the cause of death. The test should be concluded on the 7th day cost inoculation.
The surviving embryos and their CAMS are examined. If deaths or abnormality due to the inoculums occur, the seed virus is unsatisfactory.
4. Immunogenicity test : Thirteen susceptible dogs 8-14 weeks old shall be used for the test (ten vaccinates and 3 controls). Blood samples are drawn from these animals and individual sample is tested for antibodies against canine distemper. Ten dogs shall be injected with a predetermined quantity of the virus and remaining 3 dogs are used as unvaccinated controls. The dose shall be based on the virus tiltration. At least 21 days cost infection the vaccinated and controls shall be challenged intramuscularly with the same dose of virulent canine distemper virus and the animals are observed each day for 21 days. At least 2 out of 3 controls should die and survivor should show the symptoms typical of canine distemper. At least 9 out of 10 vaccinated animals should survive and should not show any clinical signs of canine distemper during the observation period. The stock seed virus should be tested for immunogenicity at least once in 5 years, if maintained under suitable conditions of storage.
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Eight days old chicken embryos from a healthy flock are inoculated on their chorioallantoic membrane with bacteriologically sterile virus suspension of egg adapted strain. After incubation for a period of five days, infected membrane and embryos are harvested. The individual embryo is tested for bacterial sterility. Those free from bacterial contamination are made into a 20 percent suspension in a suitable medium. The suspension is distributed in a single dose quantity into the ampoules of vials and freeze-dried.
The ampoules are sealed under vacuum or with pure dry sterile nitrogen before sealing. Alternatively, the virus may be grown on the suitable cell culture. Cells along with the suspending fluid is harvested, distributed in single dose quantity in ampoules and freeze dried.
4. Standard.-
(a) Description. - It is a dry product, pinkish cream material, readily dispersible in water or a suitable solvent.
(b) Identification . - It infects CAM of fertile eggs. This is neutralized by canine distemper antiserum. It does not cause distemper after injection into susceptible ferrets or dogs by immunizes them against the disease.
(c) Moisture content. - Moisture content in the finished product shall not exceed more than 1.0 per cent.
(d) Sterility test. - Shall comply with the test for sterility as described in the general monograph on “Viral Vaccines.”
(e) Safety tests. - (i) Mice safety test; Reconstituted vaccine as recommended on the label shall be tested.
Eight mice, 4 weeks old shall be inoculated intracerebally with 0.03 ml and 8 mice shall be inoculated intraperitoneally with 0.5ml. Both groups shall be observed for 7 days, if unfavourable reaction attributable to the product in either 2 or more mice in either group is observed during observation period, the batch is unsatisfactory.
(ii) Dog Safety test.-Inject two healthy dogs eight to fourteen weeks old that have previously been show to be free from distemper virus-neutralising antibodies by the recommended route with twice the dose stated on the label and observe for 21 days. No significant local or general reaction develops.
(i) Potency test. - (i) Titration : Final samples of finished product shall be tested for virus titre, and when tested at any time within the expiry period, it should contain not less than 103 ID50 per dose.
(ii) It shall be carried out in dogs. Two healthy susceptible dogs each of 8- 14 weeks of age free from distemper neutralizing antibodies are injected subcutaneously each within one vaccination dose. Serum
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samples shall be collected from each dog 14 days after vaccination and these shall have specific neutralizing antibodies at a dilution of 1: 100.
5. Labelling.- Shall comply with the requirements of labeling as laid down in the general monograph on “Viral Vaccines”.
6. Storage and expiry date. - For the freeze-dried product the expiry date is one year when stored at minus 20oC.
Avian Infectious Bronchitis Vaccine (Living)
1. Synonyms. - Avian Infectious Bronchitis Vaccine (Living) freeze-dried.
2. Definition. - It is a freeze-dried product of low virulent Avian Infectious Bronchitis Virus grown in embryonated hen’s eggs of cultivated n cell culture.
3. Preparation. - Only stock seed virus which has been established as pure, safe and immunogenic shall be used. Each jot of stock seed virus shall be tested for other pathogens by chicken embryo inoculation tests as follows: -
A lot of seed virus shall be mixed with 9 volumes of sterile heat inactivated specific anti- serum to neutralize and the vaccine virus serum mixture shall be inoculated into each of at least 20 fully susceptible chicken embryos of 9-11 days old (0.1 ml on CAM and 0.1 ml in the allantoic sac). Eggs are candled daily for 7 days. Deaths occurring during first 24 hours shall be discarded but at least 18 viable embryos shall survive 24 hours post inoculation for a valid test. All embryo and CAMS from embryos shall be examined which die after 24 hours. If necessary embryo subcultures shall be made to determine the cause of death. The test shall be concluded on the 7th day post inoculation and surviving embryos including the CAM shall be examined. If death and or abnormality attributable to the stock seed virus occur, the seed lot is unsatisfactory.
Each lot of stock seed virus shall be tested for immunogenicity as below: -
Bronchitis susceptible chickens of the same age and source shall be used. For each method of administration recommended on the label and for each serotype against which protection is claimed, 20 chicks shall be used as vaccinates. Ten additional chickens for each serotypes against which protection is claimed shall be held as unvaccinated controls. 21 to 28 days post vaccination all vaccinates and controls shall be challenged by eye drops which virulent Bronchitis virus. A separate set of vaccinates and controls shall be used for each serotype against which protection is claimed. The challenge virus shall have a titre of at least 104.6 EID50 per ml. Trachea swabs shall be taken once 5 days post challenge from each vaccinated and controls. Each swab shall be placed in test tube containing 3 ml of tryptose phosphate broth and antibiotics. The tubes and swabs shall be swirled thoroughly and stored at minus 40oC pending egg inoculation. For each chicken swabs at least 5 chicken embryos 9-11 days old shall be inoculated in the allantoic cavity with 0.2ml of broth from each tube. All the embryos surviving 3rd day post inoculation shall be used in evaluation. A tracheal swab shall be positive for virus recovery when any of the embryos show typical infections bronchitis
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virus lesions such as stunting, curling, kidney urates, clubbed down or death during 4-7 days post inoculation period.
90 percent of the controls should prove positive for virus recovery. If less than 90 per cent of the controls are negative for virus recovery, the stock seed is unsatisfactory. The stock seed virus should be tested for immunogenicity once in 5 years provided it is maintained under standard conditions of the bronchitis virus storage.
4. Standards. -
(a) Description. - It is grayish-white product easily dispersible in the diluent
(b) Identification . - (i) The contents of the ampoule are suspended as per the instructions for the field use. The 0.2ml of the suspension shall be inoculated in the allantoic cavity of 9- 11 days old chicken embryo and are incubated for 7 days. The lesions typical of infectious bronchitis shall be observed in the embryos at the end of incubation period. The allantoic fluid shall not agglutinate the chicken RBC's.
(ii) Spectilie antisera against avian infectious bronchitis virus should neutralize the vaccine virus.
(c) Moisture content. - Moisture content in the finished product should not exceed 1.0 per cent.
(d) Sterility test. - Complies with the test for sterility as described under the general monograph on “Viral Vaccines”.
(e) Safety test. - Ten healthy susceptible chickens 5-10 days old from the same source batch shall be vaccinated with ten field dose of the vaccine and along with five chicks from same batch as unvaccinated controls by the prescribed route and observed 7 or 21 days post vaccination. Neither severe respiratory sympt0ms nor death shall occur to more than one experimental chicks, none of the unvaccinated control shall show any clinical symptoms.
(f) Potency test. - The minimum virus content of the freeze-dried product shall not be less than 103.5 EID50 per bird. The virus content of the vaccine shall be titrated as below:
Serial ten-fold dilution of the freeze-dried material will be made in tryptose phosphate broth. Three to five embryonated eggs (9-11 days old) shall be in inoculated with 0.1 ml of each dilution into the allantoic cavity and observed daily for 7 days.
Deaths occurring during the first 24 hours shall be discarded. The surviving embryos are examined for the evidence of infection and EID50 shall be calculated by the Reed and Muench Method/spearman and Karber method.
5. Labelling .- Shall comply with the requirement of labeling as laid down in the general monograph on “Viral Vaccine”.
6, Storage and expiry date.- Shall be stored at 4 oC for six months].
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PART II ANTISERA
Provisions applicable to the production of all Sera from Living Animals
1. Definition- (i) This Part of the Schedule applies to antibacterial sera, anti-viral sera and anti-toxic sera which are prepared by injecting bacteria or viruses or their products into buffalo-bulls or other suitable animals so as to produce active immunity which is manifested by the formation of anti-body.
(ii) For the purpose of this Part of the Schedule an anti-serum means sterile liquid anti- serum concentrated and unconcentrated, solutions of globulins or their derivatives or solid forms which can be reconstituted when necessary.
2. Staff of Establishment- The establishment shall be under the direction and control of a competent expert in bacteriology and serology with adequate training in immunology and standardisation of biological products and knowledge of animal management. He shall be assisted by a staff adequate for carrying out the tests required during the course of preparation of the sera and standardisation of the finished products.
3. Proper Name- The proper name of he antiserum shall be the recognised scientific name of the diseases or its causative organism or some generally recognised abbreviations thereof preceded by the prefix ‘anti’, and followed by the word ‘serum; as or example, ‘Anti-anthrax serum’. The proper name of any antitoxin may be formed from the word ‘Anti-toxin’ preceded by the name of the organism from which the toxin was prepared, and followed, of desired, by a tem indicating the source or the strain of that organism provided where there is no special provision in the Schedule, the name as approved by the Licensing Authority may be adopted.
4. Records-
(1) The permanent records which the licensee is required to keep shall include the following particulars: -
(a) As to the culture- Evidence of the identity and specificity of the cultures.
(b) As to the procedure used in immunising the animals;
(i) The method of preparing the cultures or antigen used for immunisation.
(ii) The dosage and methods employed in administering the culture or antigen.
(iii) The period in the course of immunisation at which blood is withdrawn for the preparation of the serum.
(c) Any test which may have been applied to the serum to determine its content of specific antibodies or its specific therapeutic potency and purity.
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(2) If the licensee desired to treat the performance of any tests recorded under sub- paragraph (i) (c) of this paragraph as determining the date of completion of manufacture for the purpose of rule 109 he shall submit full particulars of the proposed test to the Licensing Authority and obtain his approval.
5. Cultures- The cultures used in immunis ing the animals shall be at all times open to inspection, and specimens shall be furnished for examination at the request of the Licensing Authority.
6. Quantity -
(a) Any antiserum shall be issued for veterinary use in the form of either.
(i) Actual serum, i.e., the liquid product of decantation of the coagulated blood or plasma without any addition, other than antiseptic or subtraction, or
(ii) A solution of the purified serum proteins containing the specific antibodies.
(b) At the time of issue, the liquid shall be clear or show at the most a slight opalescence or precipitate. Preparations of the natural serum shall not contain more than 10 per cent of solid matter. A solution of serum protein shall not contain more than 20 per cent of solid matter.
7. Precautions to be observed in preparations-
(i) Laboratories where sera are exposed to the air in the course of the process of preparation must be separated by a sufficient distance from stables and animals houses to avoid the risk of aerial contamination with bacteria from animal excreta, and must be rendered fly proof to prevent such contamination by insects. Such laboratories must have impervious walls and floors and must be capable of being readily disinfected when necessary.
(ii) A special room with impervious walls must be provided for the collection of blood from the living animals.
(iii) An efficient system of manure removal must be used which will prevent its accumulation in the vicinity of any room where blood or serum is collected or handled.
(iv) An adequate number of sterilizers must be provided for the sterilization of all glassware or other apparatus with which the serum may come into contact in the course of its preparation.
(v) All processes, to which the serum is subjected during and after the collection from the animals, must be designed to preserve its sterility, but in the case of a artificially concentrated sera, it shall suffice that the process of concentration is conducted with scrupulous cleanliness and in such a manner as to avoid unnecessary dangerous contamination.
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(vi) The laboratories in which the testing of sera for potency, sterility and freedom from abnormal toxicity are carried out must be adequate for the purpose. An adequate supply of animals for use in such tests and suitable housing for such animals must be provided.
(ii) Provision must be made for complying with any special conditions which may be laid down in the Schedule relating to the production and issue of the particular serum, in respect of which the lic ence is granted.
8. Unhealthy or Infected Animals- If an animal used in the production of sera is found to be suffering from an infection except one produced by living organisms against which it is being immunized, or shows signs of serious or persistent ill health not reasonably attributable to the process of immunisation, the licensee shall immediately report the matter to the Licensing Authority and shall, if the authority orders an inspection and the Inspectors so directs, cause such animals to be killed and a postmortem examination of it to be made, and take steps to prevent any serum obtained from the animal being sold or offered for sale until permission is given by the Licensing Authority. If the result of the postmortem is such as to bring under suspicion, the health of any of the other animals used for the production of sera, the Licensing Authority may prohibit the use of those animals for the production of sera or may take such other steps as may be necessary to prevent the issue of sera which may be dangerous to animal health.
Provided in the case of emergency, the person in charge of the establishment may order the destruction of an animal used in the production of sera and suspected of infection, and shall in that case given notice forthwith to the Licensing Authority and shall permit an Inspector to be present at the postmortem examination.
9. Conditions and Housing of animals-
(i) The animals used in the production of sera should be adequately housed under hygienic environments.
(ii) Only healthy animals free from disease should be used in the preparation of sera.
(iii) Every animal intended to be used as the source of serum must be subjected to a period of observation in quarantine for at least seven days before being admitted to the animal sheds in which the serum yielding animals are housed.
(iv) In case of horses and other equidae, every animal used as source of serum shall either be actively immunized against tetanus or shall be passively immunized against the disease by injection of tetanus antitoxin in such doses as to ensure the constant presence of that antitoxin in the blood during the whole period of the use of the animals as a source of serum.
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Anti-Sera and their General Standard Anti-sera contain the immune substances that have a specific prophylactic or therapeutic
action when injected into animals exposed to or suffering from a disease due to a specific microorganism or its toxin. Anti-sera are classified into three groups.
(i) Antitoxic sera (Antitoxin). (ii) Antibacterial sera. (iii) Antiviral sera.
Antisera are usually issued in an unconcentrated form for animal use but may be concentrated and also freeze dried. However, for the purpose of the Schedule the word ‘antisera’ is also used for the unconcentrated liquid sera. A suitable bacteriostatic agent in a concentration sufficient to prevent the growth of microorganisms is added to the liquid serum.
General Standard
1. Description- Liquid native or unconcentrated antisera are yellow or yellowish brown in colour. They are initially transparent but may become turbid with age. They are almost odourless except for the odour of any bacteriostatic agent that may have been added.
2. Identification- The test for identity is described in the individual monograph.
3. Acidity or Alkalinity- All native antisera have a pH of 7.0 to 8.5.
4. Abnormal Toxicity- All anti-sera shall comply with the following tests or freedom from abnormal toxicity.
(a) Two healthy mice each weighing not less than 18 g. are injected subcutaneously each with 0.5 ml. of the sample and observed for five days. None of the mice should show any abnormal reaction or die.
(b) Two healthy guinea pigs each weighing 300 g. to 450 g. are injected subcutaneously each with 5 ml. of the sample and observed for seven days. None of the guinea-p igs should show any abnormal reaction or die.
5. Sterility- All anti-sera shall comply with the tests for sterility described in rules 115 to 119.
6. Potency- The potency of each preparation, when the available methods permit, is determined by the appropriate biological assay, and it is described under the individual monograph.
7. Total Solids- Native antisera should not contain more than 10 per cent solid matter.
8. Labelling- Should comply with the provisions for ‘Labelling’ as laid down for ‘Bacterial Vaccines .’
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9. Storage- Liquid preparations of antisera shall be stored, protected from light at temperature between 2 °C to 4 °C and shall not be frozen.
10. Date of Manufacture- The date of manufacture shall be unless otherwise specified in the individual monograph in this part is as defined in clause (b) of sub-rule (3) of rule 109.
11. Containers- All antisera are distributed in sterilised containers of a material which is inert towards the substance and which are sealed to exclude micro-organisms.
12. Expiry Date- The expiry date of potency of all sera shall not be more than twenty-four months after the date of a manufacture.
Anti-Anthrax Serum
1. Synonym- Bacillus Anthracis Anti-serum.
2. Definition- Anti-anthrax serum is the serum of animals that confers a specific protection against Baccillus anthracis.
3. Preparation- The antiserum may be prepared in buffalo bulls after repeated injections of cultures of B. anthracis of a virulent strain.
4. Standard - It complies with the requirements in the general provisions for antisera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility, Solids, Labelling, Storage and Expiry date.
(i) Identification – It protects animals against infection with B. Anthracis
Anti-Blackquarter Serum
1. Synonym- Blackleg Antiserum, Clostridium Chauvoei-Anti-serum
2. Definition-Anti-Blackquarter serum is the serum of suitable animals containing the substances that have a specific neutralising effect on Clostridium Chauvoei.
3. Preparation- It is prepared by injecting subcutaneously or intramuscularly increasing doses of formolised cultures of Cl. Chauvoei into buffalo bulls.
4. Standards- It complies with the requirements described in the general provisions for antisera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility, Solids, Labelling, Storage and Expiry date.
Identification- It protects susceptible animals against infection with virulent strains of Cl. Chauvoei.
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Anti-Fowl-Cholera Serum
1. Synonym- Pasteurella Septica Antiserum (Avian).
2. Definition- Fowl Cholera Antiserum is the serum of animals containing the substances that confer a specific protection to fowls against virulent strain of Pasteurella Septica (Avian).
3. Preparation- Antiserum is prepared from buffalo bulls after they have been subjected to an injection of killed cultures of virulent strain of Pasteurella Septica (Avian) followed by injections of living cultures of the same organisms.
4. Standard - It complies with the requirements described in the general provision for anti- sera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility, Solids, Lab elling, Storage and Expiry date.
Identification- It protects susceptible fowls against infection with Pasteurella Septica (Avian) and its homologous strains.
Anti- Haemorrhagic Septicaemia Serum
1. Synonym- Pasteurella Septica Antiserum.
2. Definition- Anti-Haemorrhagic Septicaemia Serum is the serum of animals containing the substances that confer a specific protection to susceptible animals against virulent strains of Pasteurella Septica.
3. Preparation – The antiserum is prepared from buffalos who have reacted to a dose of virulent rinderpest virus, which is injected simultaneously with a predetermined quantity of antirinderpest serum so as to control the severity of the reaction (serum-simultaneous- method).
4. Standard - It complies with the requirements described in the general provisions of antisera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility, Solids, Labelling, Storage and Expiry date.
(i) Identification- It protects susceptible animals against rinderpest.
(ii) Potency -Five Buffalo -calves of about one year of age in good condition are used for the test. Three are injected subcutaneously with the anti-rinderpest serum under test at the rate of 10 ml. per 46 kg. body weight, subject to a minimum of 20 ml. per animal. These together with the two remaining are simultaneously injected subcutaneously at a different site with 1 ml. of a 1: 100 dilution of spleen suspension of virulent bull-virus.
The animals should be observed for fourteen days during which time the serum treated animals should exhibit no symptoms of rinderpest other than rise in temperature and slight intestinal disturbances, while the controls develop more severe symptoms or die.
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Salmonella Pullorum Anti Serum
1. Synonym- Salmonella Pullorum Anti Serum.
2. Definition- Salmonella Pullorum anti-serum is the sera from fowls and contains antibodies against Salmonella Pullorum. It is used for standardizing batches of Salmonella Pullorum antigens and also used as a control along with the sera suspected for pullo rum disease.
3. Preparation- The serum is prepared after intravenous inoculation with smooth culture suspension of Salmonella Pulloram in healthy birds.
4. Standards- It complies with the requirements in the general provisions for anti-sera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility, Solids, Labelling, Storage and Expiry date.
Identification - It should give positive agglutination with Salmonella pullorum antigen.
Standard Anti-Brucella Abortus Serum
1. Synonym- National counterpart of standard anti-Brucella abortus serum.
2. Definition- Standard anti-Brucella abortus serum is the serum which contains 1000 International Units (I.U) per ml. and is used for standardizing batches of brucella antigens and is also used as a control along with the sera suspected for brucellosis.
3. Preparation- The serum is prepared after intravenous inoculation of suspension of smooth culture of B. abortus culture of B. abortus (strain 99) in rabbits or cattle and subsequently diluting it suitably with brucella-free healthy serum so that when tested with standardized Brucella abortus tube test antigen, it gives 50 % agglutination at 1/500 final serum dilution.
4. Standard - It complies with the requirements in h general provision for anti-sera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility, Solids, Labelling, Storage and Expiry date.
Identification - It should give agglutination with Brucella antigen.
PART III- DIAGNOSTIC ANTIGENS
Provisions Applicable to the Manufacture andStandardisation of Diagnostic Agents (Bacterial Origin).
1 Definition- This Part of the Schedule applies to reagents of bacterial origin employed for various tests.
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2. Staff of Establishment- A competent expert in bacteriology with sufficient experience in the manufacture and standardisation of veterinary biological products shall be in charge of the establishment responsible for the production of various diagnostic agents of bacterial origin and he may be assisted by a staff adequate or carrying out the tests required during the preparation and standardisation of various diagnostic agents.
3. Proper Name- The proper name of any diagnostic agent is the name of micro-oraganism from which it is made, followed by the word ‘antigen’ unless the Schedule otherwise provides, or, it may be derived from the name of the organism responsible for the causation of the disease or if there is no special provision in the Schedule, the name approved by the Licensing Authority. In the case of the undermentioned preparations the proper name of the diagnostic agent may be as follows:-
1. Abortus Bang Ring (A.B.R. ) Antigen 2. Brucella Abortus Coloured Antigen 3. Brucella Abortus Plain Antigen. 4. Johnin 5. Mallein. 6. Salmonella Abortus Equi “H” Antigen. 7. Salmonella Pullorum Coloured Antigen. 8. Salmonella Pullorum Plain Antigen. 9. Tuberculin.
4. Records- Culture used in the preparation of diagnostic agents of bacterial origin must, before being manipulated into an agent be thoroughly tested for identity by the generally accepted tests applicable to the particular micro-organism. The permanent record which the licensee is required to keep shall amongst other include a record of the origin, properties and characteristics of the cultures.
5. Preparation- Diagnostic agents of bacterial origin are prepared from selected cultures after their careful examination for the identity, specificity, purity and antigenicity. They may be prepared in the following manner.
(a) Formolised antigens- The selected pure culture strain grown in a suitable medium at an optimum temperature for an appropriate period. The pure growth is then exposed to the action of a solution of Formaldehyde I.P. in a suitable concentration and at an appropriate temperature for a suitable period.
(b) In some cases, the diagnostic agents are prepared by growing the organisms on suitable media and then deriving specific protein constituents of the bacteria by various methods.
6. General Standard:-
(a) Description- Diagnostic agents may be clear opalescent or coloured liquids.
(b) Identification- Some exhibit specific agglutination when mixed with the serum of the animals infected with homologous organisms and others when injected into the animal body
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in appropriate doses cause specific reactions like hypersensitiveness, local and general reaction, if the animal is infected with homologous organisms.
(c) Sterility Test- All antigens shall be tested for sterility in accordance with rules 114 to 119.
(d) Standardisation- It is carried out either by determining the definite cell concentration in the product or by observing the general and local reactions in healthy and artificially infected animals with various standard dilutions of the product.
7. Labelling- As under general provisions for the bacterial vaccines with the addition that it is meant for diagnostic purposes only.
8. Storage- All antigens are stored, protected from light at a temperature between 2 ° C to 4 ° C.
9. Date of Manufacture- The date of manufacture shall be unless otherwise specified in the individual monograph in this part as defined in clause (b) of sub- rule (3) of rule 109.
Abortus Bang Bing (A.B.R.) Antigen
1. Synonym- Milk Ring Test Antigen.
2. Definition- The antigen is a suspension of pure growth culture of standard strain of Brucella abortus strain 99 strained supravitally with 2,3,5, triphenyl tetrazolium chloride suspended in 0.85 per cent saline containing 1 per cent glycerol and 1 per cent phenol.
3. Preparation- Smooth strain of Brucella abortus strain 99 is grown on potato infusions agar for 48 to 72 hours in Roux flasks, at 37 ° C. Condensation fluid if any is pipetted of before washing. Each flask is washed with about 20 ml. of normal saline. The pooled washing is filtered through a gauze and the filtrate is collected in a measuring cylinder. To every 500 ml. of the filtrate 1 g. of 2, 3, 5, triphenyl tetrazolium chloride is added immediately. The container is shaken for thirty minutes till the tetrazolium salt is dissolved. The product is taken out and kept at 37 ° C for two hours. After incubation the product is heated at 65° C in a water bath for thirty minutes. It is cooled and centrifuged at 3000 r.p.m for one hour. The supernatant is pipetted off and sediment is suspended in normal saline containing 1 per cent glycerol and 1 per cent phenol and filtered through sterile cotton wool. This forms concentrated antigens.
Standardization of the Strained Antigen
An aliquot portion of the microbial suspension stained with phenylte-trazolium is taken, representing the initial undiluted suspension. 1 ml. per tube of this initial undiluted stained suspension is added to six test tubes, followed by increasing quantities of the glycerolphenol diluent a follows:-
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Tube Undiluted Stained Suspension Diluent 1 1 0.6 2 1 0.8 3 1 1.0 4 1 1.2 5 1 1.4 6 1 1.6
The contents of each tube are then diluted tenfold with the same diluent and serve as antigen for a tube agglutination test with the Standard Serum (or its national counterpart). In this way, six sero -reactions will be carried out. During this procedure, the concentrated strained microbial suspension should be kept in the refrigerator at 4 ° C.
The agglutination reactions are read after forty -eight hours at the agglutination titre of the Standard Serum, previously determined with the usual unstained antigen in the tube test, corresponding to the correct dilution of the standard antigen.
The next step, therefore, is to dilute the concentrated stained suspension to the same extent as the tube whose tenfold dilution has given the correct agglutination titre, i.e. the concentration of antigen in the tube before the tenfold dilution had been made.
4. Standard:-
(a) Description- It is a red colour liquid containing dead bacteria in suspension.
(b) Identification- It shows formation of a specific cherry red coloured ring in the cream layer when mixed with pooled samples of milk taken from animals suffering from burcellosis.
(c) Sterility Test- Should comply with tests for sterility described in the general monograph on ‘Diagnostic Antigen’. The test shall, however, bed one before colouring.
5. Labelling and Storage- Should comply with the requirements of ‘Labelling’ and ‘Storage’ as laid down in the general monograph on ‘Diagnostic Antigens’.
6. Expiry Date- The date of expiry of potency shall be not more than nine months from the date of manufacture when stored 2 ° C to 4°C.
Brucella Abortus Coloured Antigen
1. Synonym- Brucella abortus Cotton Strain 99 coloured Antigen.
2. Definition- Brucella Abortus colured Antigen, is a suspension of pure smooth cultures of Brucella abortus strain 99 in phenolised glycerine saline, the bacteria being colo ured by the addition of crystal violet and brilliant green. This antigen is used for plate test for serological diagnosis of brucella infection.
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3. Preparation- Seventy-two hours old growth of Brucella Abortus strain ninetynine in smooth form on potato infusion agar medium in Roux flasks is washed with phenolised glycerine saline (containing 12 per cent sodium chloride, 20 per cent glycerine and 0.5 per cent phenol). The washed growth is filtered through a pad of absorbent cotton wool and the suspension is coloured by the addition of 1 ml. each of 1 per cent aqueous solution of crystal violet and brilliant green for very 250 ml. of the suspension. The product is heated for sixty minutes in a water bath at 60 °C before it is standardised.
4. Standard:-
(a) Description- It is a greenish violet liquid containing dead bacteria in suspension.
(b) Identification-It gives specific agglutination when mixed with the serum of the animal infected with brucella organism.
(c) Sterility Test- Should comply with the tests for sterility described in thegeneral monograph on ‘Diagnostic Antigens’
(d) Standardisation- 0.5 ml. of the antigen is mixed with 4.5 ml of normal saline solution in Hopkins graduated tube. The mixture is centrifuged at 3000 r.p.m. for sixty minutes and the percentage of bacterial cells present in the original antigen is assessed by noting the height of the cell deposit. The antigen is then standardised so as to contain 10 per cent cell deposit.
5. Labelling and Storage- Should comply with the requirements of ‘Labelling’ and ‘Storage’ as laid down in the general monograph on ‘Diagnostic Antigens’.
6. Expiry Date- The date of expiry of potency shall be not more than nine months from the date of manufacture when stored at 2 ° C to 4°C.
Brucella Abortus Plain Antigen
1. Synonym- Brucella Abortus Strain 99 Antigen.
2. Definition- Brucella Abortus Plain Antigen is a suspension of a pure smooth culture of Brucella abortus strain 99 in phenol-saline.
3. Preparation- Seventy-two hours old growth of Br. Abortus strain 99 in smooth form on potato infusion agar medium in Roux flasks is washed with normal saline solution. The washed growth is filtered through a pad of absorbent cotton wool and the suspension is kept at 60 ° C per cent.
4. Standard:-
(a) Description- An opalescent liquid containing dead bacteria in suspension.
(b) Identification –It gives specific agglutination when mixed with the serum of animals infected with brucella organism.
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(c) Sterility Test- Should comply with the tests for sterility described in the general monograph in ‘Diagnostic Antigen’.
(d) Standardisation- Mix the concentrated antigen well and dilute 1 ml. With 0.5 per cent phenol saline until it corresponds to about Tube 4 of Brown’s opacity tubes. Further dilutions of the antigen adjusted to opacity tube No. 4 are made. The particular dilution that gives 50 per cent agglutination with anti-brucella abortus serum ( containing 1000 Internationals Units) at 1 : 500 final serum dilution, is assessed as the diluting factor for the concentrated antigen.
5. Labelling and Storage- Should comply with the requirements of ‘Labelling and Storage’ as laid down in the general monograph on ‘Diagnostic Antigen’.
6. Expiry Date- The date of expiry of potency shall be not more than nine months from the date of manufacture when stored at 2 ° C to 4 C.
Johnin
1. Definition- Johnin is a preparation of a fluid medium in which Mycobacterium paratuberculosis has been grown in artificial culture and which has been freed by filtration from the bacilli.
2. Preparation- Young culture of selected strain of Myco. Paratuberculosis of bovine origin is grown on synthetic medium and incubated at 37 ° C for ten to twelve weeks. Flasks showing lucurient and pure growth are steamed for three hours thereafter kept at room temperature overnight. The contents are filtered through fine meshed sieve. The filtrate is concentrated over a steam bath to one-tenth of its original volume and kept in cold storage for fourteen days before being filtered through Seitz filter. The product is dispensed in ampoules and hermetically sealed.
3. Standards:-
(a) Description- A yellowish brown to brownish liquid.
(b) Identification- It produces hot, painful and oeodemateus swelling at the site of inoculation in animals infected with Myco-paratuberculosis organism.
(c) Sterility Test- Should comply with the test for sterility described in the general monograph on ‘Diagnostic Antigens’.
(d) Potency Test- Two animals, previously infected with Myco-paratuberculosis and two healthy animals are each injected intrademally in the neck region with 0.1 ml. of the product. Forty-eight hours later, the injection is repeated at the same site. The product should produjce a typical reaction in the infected animals in the form of a hot painful and oedemetous
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swelling at the site of inoculation persisting for at least forty -eight hours after the second injection. Control animals should not show such reaction.
4. Labelling and Storage- Should comply with the requirements of ‘Labelling’ and ‘Storage’ as laid down in general monograph on ‘Diagnostic Antigens’.
5. Expiry Date- The date of expiry of potency shall be not more than two years from the date of manufacture when stored at 2 ° C to 4 ° C.
Malleins
1. Definition- (i) Malleins are preparations of fluids media in which the Actinobacillus mellei has been grown in artificial culture and which have been freed by filtration from the bacilli.
(ii) For the purposes of this Schedule malleins are classified into (a) Mallein-subcutaneous and (b) Mallein intradermopalpebral (I.D.P.)
2. Preparation:-
(a) Mallein Subcutaneous- Three to four weeks old pure growth of standard strain of A. mallei grown on synthetic medium is steamed for one hour in Koch’s steam sterilizer. One part of 5 per cent phenol solution is added to every nine part of the dead culture which is then filtered through Seitz filter.
(b) Mallein Concentrated. - The procedure is the same as for Mallein Subcutaneous except, that the filtrate is evaporated in porcelain dish over steam to half the original volume before addition of phenol. Five per cent phenol solution is added in sufficient quantity to the concentrated product, to give a final concentrated of 0.5 per cent.
3. Standards: -
(a) Description- A yellowish to brown viscous liquid .
(b) Identification- It produces hot tense, painful swelling when injected into the animals infected with A. mallei organisms.
(c) Sterility Test- Should comply with the tests for sterility described in the general monograph on ‘Diagnostic Antigens’.
(d) Potency Test: -
(i) Mallein subcutaneous- Two ponies, previously sensitised with A. Mallei and controls, are injected each with 1 ml. of the product subcutaneously in the neck region. The animals are observed for local reaction and rise in temperature. Local reaction is manifested by a hot tense, painful swelling becoming prominent within twenty-four hours. The rise in temperature is observed by recording the body temperature at the time of inoculation and
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subsequently at short intervals. A rise in temperature of 1° C or more above normal is indicative of infection.
(ii) Mallein Intra-dermo-Palpebral (I.D.P.)- Two ponies, previously sensitized with A. mallei and two healthy ponies are injected intradermally with 0.2 ml. of the product near the rim of the lower eye lid of one eye. Typical reactions such as painful swelling of the palpebral tissue with mucopurulent discharge from the eye is indicative of infection. The two healthy ponies should not show such reactions.
Similar test in other eye is performed with a previously determined patient mallein using as a standard. When the local reactio ns produced by intradermo palpebral infections of the two preparations are comparable the batch is passed for issue.
4. Labelling and Storage- Should comply with the requirement of ‘Labelling’ and ‘Storage’ as laid down in the general monograph on ‘Diagnostic Antigen’.
5. Expiry Date- The date of expiry of potency shall be not more than two years from the date of manufacture when stored at 2 ° C to 4 ° C.
Salmonella Abortus Equi ‘H’ Antigen
1. Synonym- Equine Abortion Diagnostic Antigen.
2. Definition- Salmonella Abortus Equi Antigen is suspension of a pure smooth culture of actively motile Salmonella Abortus equi in formal saline.
3. Preparation- Standard stain of S.abortus equi is grown on nutrient agar in Roux flasks at 37 ° C for twenty-four hours. The pure growth in Roux flasks is washed with normal saline and diluted to contain approximately 800 million organisms per ml. Solution of Formaldehyde I.P. is added to give a final concentration 0.5 per cent and the formolised product is incubated at 37 ° C for twenty -four hours. The final product is dispensed in suitable containers.
4. Standards:-
(a) Description- A slightly opalescent liquid containing dead bacteria in suspension.
(b) Identification- It gives specific agglutination when mixed with the serum of the animals infected with S.abortus equiorganisms.
(c) Sterility Test- Should comply with the test for sterility described in the general monograph on ‘Diagnostics Antigens’.
5. Labelling and storage- Should comply with the requirements of ‘Labelling’ and ‘Storage’ as laid down in the general monograph on ‘Diagnostic Antigens’.
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6. Expiry Date- The date of expiry of potency shall be not more than nine months from the date of manufacture when stored at 2 ° C to 4 ° C.
Salmonella Pullorum Coloured Antigen
1. Synonym- Bacillary White Diarrhoes (B.W.D) Antigen.
2. Definition- The antigen is a suspension in a solution containing 1 per cent Formaline, 1 per cent KH2PO4 and 0.85 per cent Sodium Chloride of pure smooth culture of standard strain of Salmonella Pullorum.
3. Preparation- Standard strain of S. Pullorum is grown on sulphur agar medium in Roux flasks for five days at 37 ° C. The pure growth is washed with 1.0 per cent Formal Saline.
Standardisation
The antigenic cell suspension is then centrifuged (preferably in cold centrifuge) for half an hour at 4000 rotations per minute and the packed cell volume determined. The packed cell is then re-suspended in a solution containing 1 per cent formalin, 1 per cent KH2 PO4 and 0.85 per cent sodium chloride, 1 ml. of packed cell is suspended in 10 ml. of the resuspendiary solution, mixed thoroughly and is passed through a cotton wool pad. The turbidity of the antigenic suspension is usually between 100 to 125 times Mac Farland scale standard and optimum 3 cc. of a 1 per cent aqueous solution of crystal violet are added to 100 ml. of the antigenic suspension. After making the dye the antigen is allowed to stand forty-eight hours before use. The average yield per Roux flasks of culture medium is about 50 ml. The antigen should be bottled in 10 ml. or 20 ml. quantity in amber-coloured bottles and corked with rubber caps and paraffin sealed and preserved until required for use within he expiry period. This antigen reacts instantly with the blood of all carrier birds and remains permanently negative with that of non-infected birds.
This antigen gives good reactions with positive sera whose titre is even as low as 1 : 20.
4. Standard:-
(a) Description- Violet coloured liquid containing dead bacteria in suspension.
(b) Identification- It gives specific agglutination when mixed with the serum of birds in infected with S. Pullorum infection. It is used for carrying out plate agglutination tests for serological diagnosis for S. Pullorum infection in birds.
(c) Sterility Test- Should comply with the test for sterility described in the general monograph on ‘ Diagnostic Antigen’. The tests shall be done before addition of ‘Crystal Violet’.
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5. Labelling and Storage- Should comply with the requirements ‘Labelling’ and ‘Storage’ as laid down in the general monograph n ‘Diagnostic Antigens’.
6. Expiry Date- A six month expiration date for this antigen is recommended. However, it is advisable to use fresh ones as far as possible. This antigen should be preserved at 4 ° C to 6 ° C in dark place in the refrigerator and should not be exposed to hot weather condition for longer than necessary before use in the field.
Salmonella Pullorum Plain Antigen
1. Synonym- Bacillary White Diarrhoes (B.W.D) Plain Antigen.
2. Definition- The antigen is a suspension of pure smooth culture of Salmonella pullorum in phenol saline.
3. Preparation- Forty-eight hours old pure culture of smooth strain of S. Pullorum is washed with 0.5 percent phenol saline and the pooled suspension is adjusted to contain approximately 800 million organisms per ml. by the addition of more carbol saline. The suspension is kept at room temperature of twenty -four hours, and dispensed in suitable containers.
4. Standard: -
(a) Description- An opalescent liquid containing dead bacteria in suspension.
(b) Identification - It gives specific agglutination when mixed with the serum of birds infected with S. pullorum.
(c) Sterility Test- Should comply with the tests for sterility described in the general monograph on ‘Diagnostic Antigen’.
5. Labelling and Storage- Should comply with the requirments of ‘Labelling’ and ‘Storage’ as laid down in the general monograph on ‘Diagnostic Antigens’.
6. Expiry Date- The date of expiry of potency shall be not more than nine months from the date of manufacture when stored at 2 ° C to 4 ° C.
Tuberculin
(i) Tuberculines are preparations of fluid media on which Mycobacterium tuberculosis has been grown in artificial culture and which has been freed by filtration from the bacilli.
(ii) For the purposes of the Schedule tuberculines are classified in (a) Tuberculine- Subcutaneous (b) Heat Concentrated Synthetic Medium (H.C.S.M) Tuberculine (c) Avian tuberculine.
2. Preparation:-
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(a) Tuberculine subcutaneous- Flasks containing Henley and Dorset synthetic medium are inoculated with standard human strains of Myco. Tuberculosis previously grown on glycerol- beef broth medium for ten days. After ten to twelve weeks of incubation at 37 ° C, flasks containing pure growth are steamed for three hours. The contents are filtered through fine meshed sieve and the volume is made up to its original with phenolised distilled water such that the final concentration of phenol is 0.5 per cent. It is then filtered through Seitz filter.
(b) Heat Concentrated Sythetic Medium (H.C.S.M) Tuberculine- To the strained liquid obtained after sieving as in the method of preparation of Tuberculine subcutaneous, glycerol is added in the proportion of 122 ml. per litre of the original volume of medium used. The mixture is evaporated to one-fifth of the original volume on a steam bath. An equal volume of 1 per cent phenol in distilled water is added after the mixture is cooled. The product is stored at 47 ° C for fourteen days before it is filtered through Seitz filter. It is then dispensed in ampoules.
(c) Avian Tuberculine Concentrated- The procedure is the same as for Tuberculine Concentrated (H.C.S.M) except that standard strain of Myco-tuberculosis (Avian) is used in its preparation.
3. Standard:-
(a) Description- A yellowish brown viscous liquid.
(b) Identification - When injected intradermally into the animal infected with tuberculosis diffused swelling occurs depending upon the allergic status of the animal, the magnitude of dose and specificity of the product. In non-infected animals this reaction is not observed.
(c) Sterility Test- Should comply with the test for sterility described in the general monograph on ‘Diagnostic Antigens’.
(d) Potency Test- (i) Tuberculine subcutaneous-six large white guinea-p igs each weighing not less than 300-450 kg. are individually inoculated intramuscularly with 0.5 mg. (Moist growth from solid plants) of Mycobacterium tuberculosis three weeks prior to test of each batch of tuberculine; the following dilutions of (a) test tuberculine and (b) standard tuberculine are used:-
1 in 200, 1 in 400, 1 in 800 and 1 in 1600.
The six sensitized guinea pigs are depilated on one flank and after about twenty-four hours each animal inoculated intradermally with 0.2 ml. of each dilution of the two tuberculines in two rows. The reactions are read after twenty-four and forty-eight hours. When the local reactions produced by the graded inter-dermal injections of the two comparable the brew is passed for issue.
(ii) Heat Concentrated Synthetic Medium (H.C.S.M) Tuberculine-Six adult white guinea pigs each weighing not less than 300-450 kg. and sensitized three weeks previously with 0.5
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mg. (moist growth from solid plants) of Myco-Tuberculosis bovine type, injected intramuscularly are used for test of each batch. The following dilutions o f (a) test tuberculineand (b) standard tuberculine are used: -
1 in 500, 1 in 1000, 1 in 2000 and 1 in 4000.
The six sensitized guinea pigs are depilated on one flank and after about twenty-four hours each animal inoculated intradermally with 0.2 ml. of each dilution of the two tuberculines in two rows. The reactions are read after twenty-four and forty-eight hours. When the local reactions produced by the graded inter -dermal injections of the two comparable, the test tuberculine is passed for issue. The tuberculine is dispensed in ampoules.
(iii) Avian Tuberculine- Six adults fowls, with well developed wattles, sensitized at least three weeks previously by intramuscular injection with 10 mg. moist weight (from solid plants) of twenty -one days old culture of Mycobacterium tuberculosis (Avian Type) are used for potency test of each batch. In each fowl, one wattle is inoculated with 0.2 ml. of undiluted test tuberculine and the other wattle with similar quantity of undiluted standard tuberculine. The reactions in each fowl are read after twenty -four hours and forty-eight hours and if comparable the product is passed for issue.
4 Labelling and Storage- Should comply with the requirments of ‘Labelling’ and ‘Storage’ as laid down in the general monograph on ‘Diagnostic Antigens’.
5. Expiry Date- The date of expiry of potency shall be not more than nine months from the date of manufacture when stored at 2 ° C to 4 ° C.
*[SCHEDULE F (II) (See Rule 124-C)
STANDARDS FOR SURGICAL DRESSING
Synonyms.- Bandage Cloth, bleached Bandage Cloth, Rolled Bandage, Open Wove Bandage, Cotton Bandage Cloth.
Bandage Cloth consists of cotton cloth of plain weave made from machine spun yarn of suitable count to comply with a bleached count between 20 tex and 25 tex for wrap and between 25 tex and 30 tex for weft. The fabric contains no filling, sizing or dressing material. It may be supplied uncut and folded or cut to suitable size and rolled.
Description for uncut bandages.
Uncut bandages are cotton cloth of plain weave, in one continuous length showing no joints or seams, with well-formed selvedges. The cloth is bleached to a good white, is clean and odourless and reasonably free from weaving defects and form seed and leaf debris.
Description for cut bandages.
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Same as for uncut bandages, except for selvedges which shall not be included in cut bandages. In addition, both the extremes and edges of cut bandages shall be straight and evenly cut, with reasonable freedom and loose threads.
Threads per dim. - Wrap not less than 150 and weft not less than 85.
Weight in g/m2. - 57 ± 5.
Length and Width . - The length and width shall not be less than 99 per cent each of the length and width stated on the label. For cut bandages, each of the bandages in a packing complies with this requirement.
Foreign matter. - Not more than 2 per cent. Fluorescence
When viewed under screened ultra-violet light, not more than occasional points of fluorescence are observed.
_______________________________________________________________________ * Ins. as per G.O.I. Notification GSR No.318(E) dt. 01-5-1984.
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Packing, Labelling and Storage.
Bandage Cloth shall be packed securely so as to allow normal handling and transport without tearing and exposing the contents. In packages of cut and rolled bandages, each bandage shall also individually be wrapped in a suitable paper. The net content is stated on the label in terms of length and width. Bandage Cloth must be stored in packed condition protected from dust. The packings of Bandage Cloth shall be labeled prominently with the words “Non-Sterile”.
Absorbent Gauze.
Synonyms.- Gauze. Unmedicated Gauze; absorbent Cotton Gauze. Absorbent Gauze is cotton fabric of plain weave, supplied in various widths and lengths.
The Gauze is bleached and free from any sizing, dressing or filling material. The yarn used is machine spun cotton yarn, of suitable count to comply with a bleached count between 17 and 25 tex in the finished fabric.
Description.
Cotton cloth, plain weave, with a simple selvedge present in both sides to prevent unraveling of yarn. The cloth is bleached to a good white, is clean, odourless, reasonably free from fabric defects and adhering sand debris from cotton seeds and leaves, or any other foreign matter.
Threads per dm.- Wrap not less than 75 and weft not less than 55.
Weight in g/m2. - 30 ± 5
Length and width. Not less than 98 per cent each of the length and width stated on the label.
Absorbency. - Average sinking time not more than 10 seconds.
Fluorescence. - When viewed under screened ultra-violet light not more than occasional points of fluorescence are observed,
Foreign matter. - Not more than 1 per cent.
Sterility. - If sterile, the contents comply with the test of sterility.
Packing Labelling and Storage.
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Absorbent Gauze is folded and packed with such materials and so securely as to protec t its absorbency and allow normal handling and transport without tearing and exposing the contents. The net content is stated on the label in terms of length and width. The packages shall be labeled prominently with the words “Non-Sterile”. If sterile, it shall be so stated on the label, and the packing method and material shall be such as to maintain the sterility. The Absorbent Gauze must also comply with the Sterility Test. Absorbent Gauze must be stored in packed conditions protected from moisture and dust.
METHODS OF TEST
Defect in fabric.
The sample is unfolded, opened and held against diffused daylight or spread on blacktopped table to locate and identify prominently visible defects in yarn and fabric construction. The fabric shall be reasonably free from holes, slubs, snarls and naps as well as the following: -
Odour.- Misty odour, or any objectionable smell like that of chemicals or materials used in sizing and bleaching.
Skewness.- (For Bandage Cloth only) A condition where wrap and weft do not keep at right angles to each other.
Defective Selvedge. - The selvedge tearing and allowing yarn to unravel and loop formation at selvedge.
Cracks.- Prominent steaks of space or gaps between wrap or weft yarns.
Double ends.- More wrap threads woven as one, due to wrong draw.
Sloughing.- Entanglement in the fabric of a bulk of yarn that has slipped of the weft yarn due to loose widing.
Measurement of length and width.
Length is the distance from end to end, along one edge of the fabric, and width is the perpendicular distance from one edge to the opposite edge.
Length . - Fix a meter scale to a table or mark off the division of one metre on a table edge. Starting from one ed, spread the fabric flat on that table in a single layer keeping one selvedge parallel to the scale; smoothen the fabric without stretching it, to avoid creases, and mark off with a coloured pencil, on the selvedge exactly one metre. Shift the fabric and measure the same way the second metre and so on for the entire length of the fabric making a mark at each metre. Note down the total length in metres. Repeat this at the opposite selvedge, as well as on the fabric folded approximately about the middle. The average of the
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three readings is the length. For cut bandages, one measurement at the middle of the bandages by folding it length-wise will suffice.
Width. - Lay the portion of the fabric to be measured flat and smooth on the tables, but do not stretch fabric except sufficiently to render it creaseless. At the place where mark had been made on the selvedge in measuring the length measure the perpendicular distance to the opposite selvedge with a metre scale. Note the width, repeat this at every mark made in measuring the length. The average of all the readings is the width of the fabric. For cut bandages, width shall be measured at every 50 cms and average reported as width.
Threads per dm.- (For examples not less than 15 m in length).
Weft. - At the third metre from one extreme locate three places one at about 5 cm below the top selvedge, a second in the middle and third at about 5 cm below the top selvedge, a second in the middle and third about 5 cm above the bottom selvedge, all three in a vertical row. Take a rectangular plate, (made of suitable material such as plastic or aluminium) with the rectangular opening of 5 cm x 10 cm cut in it. Keep the plate on the fabric horizontally so that the left 5 cm side and bottom (10 cm side) edges of the opening coincides with a weft and length of 10 cm. Repeat this at the other two selected places, and note down the average of three readings. Repeat this at every third metre in the sample and calculate the average weft per dm.
Warp.
Keep the rectangular plate, this time vertically with left (10 cm side) and bottom (5 cm side) edge of opening coinciding with a weft and wrap yarn respectively. Count the number of wrap yarns within the opening for 10 cm and note down. Repeat this for about 10 selected places in the samples taking care that the same set of wrap yarns is not counted more than twice and calculate the average wrap per dm. Magnifying glass mounted on stand may be used for counting.
For examples les than 15m in length, locate as many different places as the dimension of the fabric permits, the total being not less than 10 for each sample and calculate the wrap and weft per dm. as above.
For cut bandages, all the wrap threads in the samples are counted, taking care to leave 5mm at the cut edge, and weft is counted at every 50 cm at any place about the middle of the bandage.
Weight per unit area.
For samples not less than 15 m in length, cut out pieces of fabric from the entire length of sample, representative places being taken from areas at every third or fourth metre so that the total area of all the pieces so collected is not less than 3 sq metre. Weigh the pieces accurately, measure the dimension of each of the pieces and calculate the area and weight of all the pieces. From the average area and average of weight thus obtained, calculate the area per sq metre.
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For examples less than 15 m length, take pieces in such a manner that the total area of the selected pieces is not less than 20 per cent of the total area of the sample.
For cut bandages, pieces of 50 cm in length, cut from 5 different cut bandages in a packing should be taken and weight calculated as an average of 5 readings.
Absorbency. - Take a glass trough of approximate size length 30 cm x width 30 cm x depth 25 cm with straight thick walls and flat bottom. Fill it almost full with distilled water leaving only about 5 cm from the top rim of trough. Maintain the water at 27 oC ± 1oC.
Cut out from any five places located equidistant down the length of the entire sample, square pieces, each weighting one gm (±10 per cent). Fold each piece in such a manner that a square of approximately 5 cm x 5 cm is obtained. Keep one of the folded test specimen between two glass plates and place 1 kg weight on the top for 10 minutes. Remove the weight. Lift the specimen with forceps and gently place it on to the surface of water (the specimen should be lightly pinched in the middle with a blunt forceps having no serrations). As soon as the specimen touches the water surface start a stopwatch which is stopped when the entire sample disappears below the surface of the water. Record the time taken. Repeat the test with the other four-test specimens. Calculate the average time in seconds.
Foreign Matter.
Dry about 5 g of the sample to constant weight at 105oC and weigh the dried sample accurately. Extract the dried sample with chloroform for one hour in an apparatus for the continuous extraction of drugs. Remove the extracted sample to a beaker and allow the evaporation of residual chloroform. Wash the material 12 times with hot water, using about 1000 ml for each washing and wringing the material by hand after each washing; pass all water through a fine sieve (100 mesh). Place the washed material and any loose threads or fibres from sieve in a beaker, cover with a 0.5 per cent aqueous solution of distance and maintain at 50oC until free from starch. Allow to cool, filter the solution through a sieve; return sample and loose material to constant weight at 105oC, and determine the loss in weight. Calculate the percentage of foreign matter, which is equal to the loss in weight, with reference tot the sample dried to constant weight, at 105oC.
If the sample is tested with iodine and is known to be free from starch, the treatment with solution of diastase and the second series of washing with hot water may be omitted .
Cloth for manufa cture of Plaster of Paris Bandages, cut and uncut.
Synonyms.- Bleached bandage Cloth for Plaster of Paris, Rolled Bandage for Plaster of Paris.
Cloth for Plaster of Paris Bandages shall consist of cotton cloth of leno weave made from yarn of suitable count. It may be supplied cut or uncut of various widths and lengths.
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Description
(a) For uncut bandages.- Cotton cloth of leno weave, in one continuous length showing no joints or seams, and with selvedges. The cloth is bleached to a good white, is clean and odourless and reasonably free from weaving defects as well as from seed and leaf debris; the cloth may be dressed if necessary and if so, shall not dust off when unrolled.
(b) For cut bandages. - Same as for uncut bandages except for selvedges which shall not be included and the bandages shall be cut evenly with straight edges and be reasonably free from loose threads.
Threads per dm: Warp . - Average not less than 150/dm and Weft.- average not less than 75/dm. Weight in gm/m 2: - 35±5
Length andwidth: The length and width for uncut bandages shall not be less than 98 per cent each of the
length and width stated. For cut bandages a tolerance of ±5 cm in length and ±0.5 cm in width may be allowed, and each of the bandages in packing complies these requirements.
Fluorescene When viewed under screened ultra-violet light not more than occasional points of
fluorescence are observed.
Packing, Labelling and Storage Bandage Cloth for Plaster of Paris shall be packed securely so as to allow normal handling
and transport without tearing and exposing the contents. In packages of cut and rolled bandages, each bandage shall also individually be wrapped in suitable paper. The package shall be labeled as “Cloth for Plaster of Paris Bandage”. The net content is stated on the label in terms of number of rolls and length and width. Bandage Cloth for Plaster of Paris must be stored in packed condition protected from dust.
*[SCHEDULE F (III)] (See Rule 124-D)
STANDARDS FOR UMBILICAL TAPES
(A) Standards for Sterilised Umbelical Polyster Tape--
Description. - A uniform stand of Polyester yarn prepared by braiding and may be finished with a suitable silicone finishing material, white to yellowish-white in colour. Tape shall be sterilized by Gamma Radiation or by any other suitable method approved by the Licensing Authority.
Other requirements. - The Umbilical Polyester Tape shall conform to the claims made on the label in respect of length and width. ___________________________________________________________________ *Ins. as per G.O.I. Notification GSR No.1115(E) dt. 30-9-1986.
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Tensile strength. - The Umbilical Polyester Tape shall have Tensile strength of not less than 4 kgs on straight pull.
Packing and labeling. - The Umbilical Polyester Tape shall be packed in sealed Polythene bags or sealed plastic containers which ensure that when packed, the tape is sterile. The packing shall protect the tape from contamination and damage. Every packing offered for sale shall bear a clear and permanent marking with the following particulars: -
(i) The proper name of the drug i.e. Umbilical Polyester Tape ‘Sterile’ (ii) Manufacturer’s name and address. (iii) Batch number (iv) Licence number under which the tape is manufactured (v) Date of manufacture and date of expiry. (vi) Length and width of the Tape
Storage condition. - It should be stored in a cool place protected from light.
(B) Standards for Sterilised Umbelical Cotton Tape---
Description. - A uniform strand f cotton yarn prepared by braiding and may be finished with a suitable silicone finishing material, white to yellowish-white in colour. The tape shall be sterilized by Gamma Radiation or by any other suitable method approved by the Licesing Authority.
Other Requirement. - The Umbilical Cotton Tap e shall conform to the claims made on the label in respect of length and width.
Tensile strength. - The Umbilical Cotton Tape shall have a Tensile strength of not less than 4 kg on straight pull.
Packing and labeling. - The Umbilical Cotton Tape shall be packed in sealed Plythene bags or sealed plastic containers which ensure that when packed the tape is sterile. The packing shall protect the tape from contamination and damage. Every packing offered for sale shall bear a clear and permanent marking with the following particulars:-
(i) The proper name of drug i.e. Umbilical Cotton Tape “Sterile”. (ii) Manufacturer’s name and address (iii) Batch number (iv) Licence number under which the tape is manufactured (v) Dateof manufacture and the date of expiry (vi) Length and width of the Tape.
Storage condition.- It should be stored in a cool place protected from light.]
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PART IV GENERAL
1. For the purpose of this Schedule any test or method of testing describ ed in the British Veterinary Codex shall be deemed to be a method approved by the Licensing Authority.
2. The Licensing Authority shall publish in the official Gazette from time to time particulars of any test or method of testing approved by him.
1SCHEDULE FF ( See rule 126-A)
Standards for ophthalmic preparations.
Part-A. Ophthalmic Solutions and suspensions.
Ophthalmic Solutions and Suspensions shall-
(a) be sterile when dispensed or when sold in the unopened container of the manufacturer, except in case of those ophthalmic solutions and suspensions which are not specifically required to comply with the test for ‘Sterility’ in the Pharmacopoeia.
(b) contain one or more of the following suitable substances to prevent the growth of micro -organisms.
(i) Benzalkonium Chloride, 0.01 per cent (This should not be used in solutions of nitrates or salicylates).
(ii) Phenyl mercuric nitrate, 0.001 per cent. (iii)Chlorbutanol 0.5 per cent. (iv)Phenyl ethyl alcohol 0.5 per cent.
Provided that solutions used in surgery shall not have any preservative and be packed in single dose container.
Provided further that the Licensing Authority may in his discretion authorise the use of any other preservative or vary the concentration prescribed on being satisfied that its use affords equal guarantee for preventing the growth of micro-organisms:-
(c) be free from foreign matter.
(d) be contained in bottles made of either neutral glass or soda glass specially treated to reduce the amount of alkali released when in contact of aqueous liquids, or in suitable plastic containers which would not in any way be incompatible with the solutions.
1Amended under Govt. of India, Ministry of Health, F.P., W.H. and U.D. Notification No. F-1-13/69-D dt. 3- 1-70.
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The droppers to be supplied with the containers of ophthalmic solutions and suspensions shall be made of neutral glass or of suitable plastic material and when supplied separately shall be packed in sterile cellophane, or other suitable packings.
(e) In addition to complying with the provisions of labelling laid down in the rules the following particulars shall also be shown on the label:-
(1) of the containers
(i) The statement ‘Use the solution within one month after opening the container’. (ii) Name and concentration of the preservative, if used. (iii) The words ‘NOT FOR INJECTION’.
(2) of container or carton or package leaflet
(i) Special instructions regarding storage, wherever applicable. (iii) A cautionary legend reading as
"WARNING” (i) if irritation persists regarding storage, wherever applicable.
(ii) Do not touch the dropper tip or other dispensing tip to any surface since this may contaminate solutions”.
Part-B. Ophthalmic Ointments Ophthalmic Ointments shall-
(a) be sterile when dispensed or when sold in the unopened container of the manufacturer.
(b) be free from foreign matter.
(c) in addition to complying with the provisions for labelling laid down in the rules the following particulars shall be shown on the container or carton or package leaflet-
(i) Special instructions regard ing storage wherever applicable. (ii) A cautionary legend reading
“Warning :- If irritation persists or increases discontinue the use and consult physicians”].
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*[SCHEDULE G] (See Rule 97)
Aminopterin L-Asparaginase Bleomycin Busulphan; its salts Carbutamide Chlorambucil;its salts Chlorothiazide and other derivatives of 1, 2, 4 benzothiadrazine Chlorpropamide; its salts Chlorthalidone and other derivatives of Chlorobenzene compound. **[(Cis-Platin)] Cyclophosphamide; its salts **[(Cytarabine)] Daunorubicin Di-Isopropyl Eluorophosphate Disodium Stilboestrol Diphosphate Doxorubicin Hydrochloride Ethacrynic acid, its salts Ethosuximide Glibenclamide Hydantoin; its salts, its derivatives, their salts Hydroxyurea Insulin, all types **[(Lomustine Hydrochloride}] Mannomustine; its salts Mercaptopurine; its salts Metformin; its salts Methsuximide Mustine, its salts Paramethadione Phenacemide Phenformin; its salts 5-Phenylhydantoin; its alkyl and aryl derivatives, its salts Primidone **[(Procarpazine Hydrochloride]) Quinthazone Sarcolysine **[(Sodium 2 Mercaptoethanesulfonate Tamoxiten Citrate]) Testolactone __________________________________________________________
*Subs. by G.O.I Notification G.S.R. No.462(E) dt 22-06-1982 w.e.f. 22.06.1982. **Ins. by G.O.I. Notification G.S.R. No.626(E) dt 2-7-1987 w.e.f. 2-7-1987.
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Thiotepa Tolbutamide Tretamine; its salts Troxidone Antihistaminic substances the following, their salts, their derivatives, salts of their derivatives. Antazoline Bromodiphenhydramine Buclizine Chlorcyclizine Chlorpheniramine Clemizole Cyproheptadine Diphenhydramine Diphenyl pyraline Doxylamine Succinate Isothipendyl Mebhydrolin Napadisylate Meclozine Pheniramine Promethazine Thenalidine Triprolidine Substance being tetra-N-substituted derivatives of Ethylene Diamine or Prophylenediamine.
Note . – Preparations containing the above substance excluding those intended for topical or external use are also covered by this schedule.
♦[SCHEDULE H (See Rules 65 and 97)
PRESCRIPTION DRUGS
Acebutolol Hydrochloride Aclarubicin Inj Actilyse Acyclovir Adrenocorticotrophic hormone (ACTH) Alclometasone Dipropiponate Allopurinol Alphachymotrypsin Alprazolam Amantadine Hydrochloride
♦ Subs. by G.O.I Notification G.S.R. No.282(E) dt 16.07.1996 .
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Amikacin Amiloride Hydrochloride Amineptine Aminoglutethimide Tab Aminosalicylic Acid Amiodarone Hydrochloride Amitriptyline, its salts Amoscanate Amoxapine_ Amrinone Lactate Analgin Androgenic, Anabolic, Oestrogenic and Progestational Substances Antibiotics Aprotinin Organic Compound of Arsenic for injection. Articaine Hydrochloride Astemizole Atenolol Atracrium Besylate Injection Auranofin Azathioprine
Barbituric acid, its salts, derivative of Barbituric acid, their salts Bacampicillin Benserazide Hydrochloride Betahistine Dihydrochloride Bethanidine Sulphate Bezafibrate Biclotymol Biperiden Hydrochloride Bitoscanate Bleomycin Oil Suspension Bromhexine Hydrochloride Bromocriptine Mesylate Budesonide Bupivacaine Hydrochloride Buspirone
Captopril Carbidopa Carbocisteine Carboplatin Injection Carboquone Carisoprodol L.Carnitine Cefadroxyl
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Cefatoxime Sodium Cefazolin Sodium Ceftazidime Pentahydrate Ceftizoxime Sodium Sterile Cefuroxime Cefuroxime Axetil Centbutindole Centchroman Ciclopirox Olamine Clindamycin Cimetidine Cinnarizine Ciprofloxacin HCL Monohydrate/lactate Chlordiazepoxide, its salts Chlormezanone Chlorpromazine, its salts Chlorzoxazone Clavulanic Acid Clidinium Bromide Clobetasol Propionate Clobetazone 17-Butyrate Clofazimine Clofibrate Clonidine Hydrochloride Clopamide Clostebol Acetate Clotrimazole Codeine, its salts and derivatives Colchicine Corticosteroids, their esters, their derivatives and their dosage forms. Cotrimoxazole Cyclanadelate Cyclosporin Oral Solution
Danzol Dapsone, its salts and derivatives Desogestrol Dextranomer Dextropropoxyphene, its salts Diazepam Diazoxide Diclofenac Sodium Digoxine Dilazep Hydrochloride Diltiazem Dinoprostone Diphenoxylate, its salts
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Disopyramide Domperidone Dopamine Hydrochloride Dothiepin Hydrochloride Doxapram Hydrochloride Doxepin Hydrochloride
Econozole Enalapril Maleate Enfenamic Acid Epinephrine, its salts Epirubicine Inj. Ergot, alkaloids of, whether hydrogenated or not, their homologues, any salt of any substance falling within this item. Estradiol succinate Estramustine Phosphate Capsule. Ethacridine Lactate Ethambutol Hydrochloride Ethamsylate Ethinyloestradiol Ethionamide Etomidate Etoposide Cap. & Inj.
Farmotidine Flavoxate Hydrochloride Flufenamic acid, its salts, its esters, their salts Flunarizine Hydrochloride Flupenthixol Fluphenazine Enanthate and Decanoate Flurazepam Flurbiprofen Flutamide Fluoxetine Hydrochloride
Galanthamine Hydrobromide Gallamine, its salts, its quaternary compound Gemfibrozil Genodeoxycholic Acid Gliclazide Glucagon Glycopyrrolate GlydiazinamideGuanethidine Gugulipid Halogenated Hydroxyquinolines Haloperidol Heparin
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Hepatitis B. Vaccine Hyaluronidase Hydrocortisone 17-Butyrate Hydrotalcite Hydroxyzine, its salts
Ibuprofen Imipramine, its salts Indapamide Indomethacin, its salts Insulin Human Interferon Alpha Inj. Intralipid (intravenous Fat Emulsion) Iohexol Sterile Solution Iopamidol Sterile Solution Iopromide Iron Preparation for parenteral use Isocarboxazid Isoflurane Isonicotinic acid hydrazine and other hydrazine detivatives of isonicotinic acid, their derivatives, their salts. Isosorbide Dinitrate Isosorbide Mononitrate Isozsurprine
Ketamine Hydrochloride Ketoconazole Acetate Ketoprofen
Labetalol Hydrochloride Levarterenol, its salts Levodopa Lidoflazine Lithium Carbonate Lofepramine Decanoate Loperamide Lorazepam Loxapine
Mebendazole Mebeverine Hydrochloride Medroxy Progesterone Acetate Tablets Mefenamic Acid, its salts its ester, their salts Megestrol Acetate Meglumine Iocarmate Melagenina Lotion Mephenesin, its esters
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Mephentermine Mesterolone Methicillin Sodium Methocarbamol Metoclopramide Metoprolol tartarate Metrizamide Metronidazole Mexiletine Hydrochloride Mianserin Hydrochloride Miconazole Minocycline Minoxidil Mitoxantrone Hydrochloride Mometasone Furoate Morphazinamide Hydrochloride
Narcotic Drugs listed in the Narcotic Drugs and Psychtropic Substances Act 1985. Nadolol Nalidixic Acid Naproxen Natamycin Netilmicin Sulphate Nicergoline Nifedipine Nimustine Hydrochloride Nitrazepam Nitroglycerin Injection Norethisterone Enanthate Injection Norfloxacin
Ofloxacin Orphenadrine, its salts Orthoclone Sterile Oxazepam Oxazolidine,its salts Oxethazaine Hydrochloride Oxolinic Acid Oxprenolol Hydrochloride Oxyfedrine Oxymetazoline Oxyphenbutazone Oxytocin Ozothine Pancuronium Bromide Para amino benzene sulphonamide its salts and derivatives. Para amino Salicylic acid, its salts, its derivatives
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D-Penicillamine Pentazocine Pentoxiflylline Pepleomycin Injection. Phenelzine, its salts Phenothiazine, derivatives of and salts of its derivatives Phenobarbital Phenylbutazine, its salts. Pimozide Pindolol Piracetam Piroxicam Pituitory gland, the active principles of, not otherwise specified in this Schedule and their salts Polidocanol Injection Polyestradiol Phosphate Injection Praziquantel Prednimustine Tablets Prednisolone Stearoylglycolate Prenoxdiazin Hydrochloride Promazine Hydrochloride Propafenon Hydrochloride Propranolol Hydrochloride Protristyline Hydrochloride Pyrazinamide Pyrvinium, its Salts
Quinidne Sulphate
Ranitidine Rauwolfia alkaloids, their salts,derivatives of the alkaloids of rauwolfia, their salts Reproterol Hydrochloride Rosoxacin
Salbutamol Sulphate Salicylazosulphapyridine Satranidazole Septopal Beads & Chains Serratio Peptidase Sisomicin Sulphate. Sodium Cromoglyate Sodium Hyaluronate Solution Sodium and Meglumie Iothalamates Sodium Valproate Sotalol Spectinomycin Hydrochloride Spironolactone
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Sucralfate Sulphadoxine Sulphamethoxine Sulphamethoxypyridazine Sulphaphenazole Sulprostone Injection
Teratolol Hydrochloride Terbutaline Sulphate Terfenadine Terizione Testosterone Undecoanoate Tiaprofenic Acid Timolol Maleate Tinazoline Tinidazole Thiacetazone Thiopropazate, its salts Tobramycin Tranylcypromine, its salts Trazodone Tretinoin Trifluperazine Trifluperidol Hydrochloride Trimetazidine Dihydrochloride Trimipramine Tripotassium Dicitrate Bismuthate
Urokinase
Vasopressin Vecuronium Bromide Injection Verapamil Hydrochloride
Xipamide
Zidovudine Cap
NOTE 1.Preparations exempted under proviso to para 2 of Note to Schedule X shall also be covered by this Schedule. *[2.Preparations containing the above substances excluding those intended for topical/or external use are also covered by this Schedule. The inclusion of a substance in Schedule H does not imply or convey that substance is exempted from the provisions of Rule 122-A.]
_________________________________________________________________________________ * Subs. by G.O.I. Notification No. GSR 904(E) dt 1.2.2000
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SCHEDULE. I [See Rule 101 (4)]
PARTICULARS AS TO PROPORTION OF POISION IN CERTAIN CASES ♦[Omitted]
(♦ Omitted by GOI Notification No. G.S.R 462(E) dt 22.6.1982
♦♦ [SCHEDULE J
(See rule 106)
Diseases and ailments (by whatever name described) which a drug may not purport to prevent or cure or make claims to prevent or cure.
1. AIDS 2. Angina Pectoris 3. Appendicitis 4. Arteriosclerosis 5. Baldness 6. Blindness 7. Bronchial Asthma 8. Cancer and Benign tumour 9. Cataract 10. Change in colour of the hair and growth of new hair. 11. Change of Foetal sex by drugs. 12. Congenital malformations 13. Deafness 14. Diabetes 15. Diseases and disorders of uterus. 16. Epileptic-fits and psychiatric disorders 17. Encephalitis 18. Fairness of the skin 19. Form, structure of breast 20. Gangrene 21. Genetic disorders 22. Glaucoma 23. Goitre 24. Hernia 25. High/low Blood Pressure 26. Hydrocele 27. Insanity 28. Increase in brain capacity and improvement of memory. 29. Improvement in height of children/adults.
__________________________________________________________________________________ .♦♦ Subs by GOI Notification No. G.S.R. 21(E) dt 11.1.1996.
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30. Improvement in size and shape of the sexual organ and in duration of sexual performance
31. Improvement in the strength of the natural teeth. 32. Improvement in vision 33. Jaundice/Hepatitis/Liver disorders 34 Leukaemia 35. Leucoderma 36. Maintenance or improvement of the capacity of the human being for sexual
pleasure. 37 Mental retardation, subnormalities and growth 38. Myocardial infarction 39. Obesity 40. Paralysis 41. Parkinsonism 42. Piles and Fistulae 43. Power to rejuvinate 44. Premature ageing 45. Premature greying of hair 46. Rheumatic Heart Diseases 47. Sexual Impotence, Premature ejaculation and spermatorrhoea 48. Spondylitis 49. Stammering 50. Stones in gall-bladder, kidney, bladder 51. Vericose Vein. ]
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SCHEDULE K [ See Rule 123]
Class of Drugs Extent and Conditions of Exemption 1. Drugs falling under clause (b) (i)
of Section 3 of the Drugs & Cosmetics Act not intended for medicinal use.
All the provisions of Chapter IV of the Act and the Rules thereunder subject to the conditions that the drug is not sold for medicinal use or for use in the manufacture of medicines and that each container is labelled conspicuously with the words “NOT FOR MEDICINAL USE”.
2. [Omitted]……… (Omitted by Government of India Notification No. F.1-56/47-D dated 16.1.1950).
1[2A Quinine and other antimalarial drugs.
Persons selling the drug by retail under arrangements made by State Government for sale and distribution of the drugs will be exempted from the requirement to take out licences for retail sale under clause (c)2 of Section 18 of the Act.
3. 4.
3[ * * *] 3[ * * *]
4[5. Drugs supplied by a registered medical practitioner to his own patient or any drug specified in Schedule C supplied by a registered medical practitioner at the request of another such practitioner if it is specially prepared with reference to the condition and for the use of an individual patient provided the registered medical practitioner is not (a) keeping an open shop or (b) selling across the counter or
All the provisions of Chapter IV of the Act and the Rules made thereunder, subject to the following conditions: 5[(1)The drugs shall be purchased only from a dealer or a manufacturer licenced under these rules and records of such purchases showing the names and quantities of such drugs together with their batch numbers and the names and addresses of the manufacturers shall be maintained. Such records shall be open to inspection by an Inspector appointed under the Act, who may, if necessary, make enquiries about purchases of the drugs and may also take samples for test.
1Added under G.O.I. Notification No .F. I-2/47-D dated 13-2-1950. 2Amended under G.O.I. Notification No. F. I-22/59-D dated. 9-4-1960. 3Omitted by G.O.I. Notification No. F.I-6/62-D dated 2-7-69. 4Amended under G.O.I. Notification No.F.I-22/59-D dated 9-4-1960. 5Amended by Min. of Health & F.W. Notification No. X- 11013/3/76-D & MS. Dated 19-8-7824-817DGHS/77
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Class of Drugs Extent and Conditions of Exemption
(c) engaged in the importation, manufacture, distribution or sale of drugs in the provision of Chapter IV of the Act and the rules thereunder.
(2) In the case of medicine containing a substance specified in 1[Schedule G, H or X] the following additional conditions shall be complied with]
(a) the medicine shall be labelled with the name and address of the registered medical practitioner by whom it is supplied
(b) if the medicine is for external application, it shall be labeled with the words 2[* * * ] “For external use only” or if it is for internal use with the dose
(c) the name of the medicine or ingredients of the preparation and the quantities thereof, the dose prescribed, the name of the patient and the date of supply and the name of the person who gave the prescription shall be entered at the time of supply in register to be maintained for the purpose
(d) the entry in the register shall be given a number and that number shall be entered on the label of the container;
(e) the register and the prescription if any on which the medicines are issued shall be preserved for not less than two years from the date of the last entry in the register or the date of the prescrip tion as the case may be.
3[(3) The drug will be stored under proper storage conditions as directed on the label.]
5.A Drugs supplied by a hospital or dispensary maintained or supported by Government or local body 4 [* * *]
The provisions of Chapter IV of the Act and the Rules thereunder which require them to be covered by a sale licence, subject to the following conditions :
_______________________________________________________________________ 1 Subs.as per G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 2 Omitted as per G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 3 Ins. as per G.O.I. Notification No. GSR 460(E) dt 22.6.1984. 4 Omitted as per G.O.I. Notification No. GSR 812(E) dt 14.11.1994.
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Class of Drugs Extent and Conditions of Exem ption (1) the dispensing and supply of drugs shall be
carried out by or under the supervision of a qualified person;
(2) the premises where drugs are supplied or stocked shall be open to inspection by an Inspector appointed under the Drugs & Cosmetics Act who can, if necessary, take samples
(3) the drugs shall be stored under the proper storage conditions.
1[(4) The drugs shall be purchased from a manufacturer or a dealer licensed under these rules or received as transferred stocks from hospital stores for distribution. Records of such purchases or receipts shall be maintained.]
2[5.B Whole Human Blood I.P. and/or its components stored for transfusion by a First referral Unit Community Health Centre, Primary Health Centre and Hospital
The provisions of Chapter IV of the Act and the rules made thereunder which require obtaining of a licence for operation of a blood bank or processing Whole Human Blood and, or its components subject to the following conditions, namely.
(1) The First Referral Unit, Community Health Centre, Primary Health Centre and/or any Hospital shall be approved by the State/Union Territory Licensing Authority after satisfying the conditions and facilities through inspection.
(2) The captive consumption of Whole Human Blood I.P or its components in the First Referral Unit, Community Health Centre, Primary Health Centre and/or any Hospital shall not be more than 2000 units annually.
1 Ins. as per G.O.I. Notification No. GSR 648(E) dt 16.9.2002 w.e.f.01.10.2002. 2 Ins. as per G.O.I. Notification No. GSR 909(E) dt 20.11.2001
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Class of Drugs Extent and Conditions of Exemption (3) The Whole Human Blood and/or its
components shall be procured only from Government Blood Bank and/or Indian Red Cross Society Blood Bank and/or Regional Blood Transfuion Centre duly licenced.
(4) The approval shall be valid for a period of two years from the date of issue unless sooner suspended or cancelled and First Referral Unit, Community Health Centre, Primary Healthy Centre or the Hospital shall apply for renewal to the State Licensing Authority three months prior to the date of expiry of the approval.
(5) The First Referral Unit, Community Health Centre, Primary Health Centre and/or any Hospital shall have the following technical staff for storage of blood or its components:- (a) A trained Medical Officer for proper
procurement, storage and cross matching of blood and/or its components. He/she shall also be responsible for identifying haemolysed blood and ensure non-supply of date expired blood or its components.
(b) A blood bank Technician with the qualification and experience as specified in Part XII B of Schedule F or an experienced laboratory technician trained in blood grouping and cross matching.
(6) The First Referral Unit, Community Health Centre, Primary Health Centre and Hospital shall have an area of 10 sq metres. It shall be well lighted, clean and preferably air- conditioned. Blood bank refrigerator of approximate capacity fitted with alarm device and temperature indicator with regular temperature monitoring shall be provided to store blood units between 2oC to 8oC and if the components are proposed to be stored, specialized equipments as specified in Part XII B of Schedule F shall also be provided.
450
Class of Drugs Extent and Conditions of Exemption (7) The First Referral Unit, Community Health
Centre, Primary Health Centre and Hospital shall maintain records and registers including details of procurements of Whole Human Blood I.P and/or blood components, as required under Part XII B of Schedule F.
(8) The First Referral Unit, Community Health Centre, Primary Health Centre and Hospital shall store samples of donors blood as well as patients sera for a period of seven days after transfusion.]
6. Omitted as per G.O.I. Notification No. GSR 681(E) dt 5.12.1980.
7. Quinine Sulphate The provision of sub-section (a) (i) of Section 18 of the Act to the following extent.-
(i)
(ii)
The colour of the drug may be pink, owing to its being coloured with an edible pink colouring matter. The B.P tests for readily carbonisable substances product a yellow colour of an intensity about four times the colour produced with quinine sulphate conforming to the B.P. standard;
(iii) Other Cinchona alkaloids present shall not exceed six per cent; and
(iv) The residue on incineration shall not exceed 0.14 per cent.
19. Magnesium Sulphate The provision of sub-clause (i) of clause (ii) of Section 18 of the Act to the following extent. Chlorides present in the salt shall not exceed 0.12 per cent in the case of, the produce prepared from sea water
210. The following substances which are used both as articles of food as well as drugs:-
All provisions of Chapter IV of the Act and the Rules thereunder.
1 Added as per G.O.I. Notification No.F.I-19/50-DS dt 30.3.1953 2 Added as per G.O.I. Notification No. DR/Sch. Ddk/F. I-40/54-DS dt 27.1.1955.
451
Class of Drugs Extent and Conditions of Exemption (i) all condensed or powdered milk
whether pure skimmed or malted, fortified with vitamins and minerals or otherwise
(ii) Farex, Oats, and all other similar ceral preparations whether fortified with vitamins or otherwise excepting those for parenteral use.
(iii) Virol, Borvil, Chicken essence and all other similar predigested foods.
1(iv) Ginger, Pepper, Cumin. Cinnamon and all other similar spices and condiments unless they are specially labelled as con-forming to the standards in the Indian Pharmacopoeia or the official pharmacopoeias and official compendia of drug standards prescribed under the Act and Rules made thereunder.
212. Substances intended to be used for destruction of vermin or insects, which cause disease in human beings or animals viz. Insec ticides and Disinfectants.
The provisions of Chapter IV of the Act and the Rules there under which required them to be covered by a sale licence [subject to the conditions that provision of condition (17) of rule 65 of the Drugs and Cosmetics Rules, 1945 are complied with by the person stocking or selling such substances].
3 [13. The following household remedies namely.- 4[(1) Aspirin Tablets.] 5[(2) Paraetamol Tablets.]
The provision of Chapter IV of the Act and the Rules there under which require them to be covered with a sale licence in Form 20-A subject to the following conditions: -
_________________________________________________________________ 1 Amended by G.O.I. Notification No. GSR 19 dt 7.1.1978. 2 Amended by G.O.I. Notification No. F.1-20/60-D, dt 24.1.1964. 3 Ins. by G.O.I Notification No. F.1-19/59/D, dt 13.6.1961. 4 Amended by G.O.I. Notification No. S.O. 2139 dt 12.8.1972. 5 Subs. by G.O.I. Notification No. 1060(E) dt 5.9.1986.
452
Class of Drugs Extent and Conditions of Exemption (3) Analgesic Balms. (4) Antacid Preparations (5) Gripe Water for use of infants. (6) Inhealers, containing drugs for
treatment of cold and nasal congestion.
(a)
(b)
The drugs are sold only in a village having population of not more than one thousand persons and where there is no licenced dealer under the Drugs and Cosmetics Act; The drugs do not contain any substance specified in 1[Schedules G, H or X];
7) Syrups, lozenges, pills and tablets for cough.
8) Liniments for external use. 9) Skin ointments and ointments for
burns. 10) Absorbent cotton wool, bandages
absorbent gauze and adhesive plaster.
11) Castor Oil, liquid Paraffin and Epsom Salt.
12) Eucalyptus Oil 13) Tincture Iodine. Tincture Benzoin
Co.and Mercurochrome in con- tainers not exceeding 100 ml.
14) Tablets of Quinine Sulphate I.P. 15) Tablets of Iodochlorohydroxy
quinoline – 250 mg.]
(c)
(d)
the drugs are sold in the original unopened containers of the licenced manufacturers;
when the drugs are sold under clause (a) condition 3 under “Conditions of licence” of Form 20-B shall not apply.
214 Mechanical Contraceptives
The provisions of Chapter IV o the Act and Rules thereunder, which require them to be covered by a sale licence, [subject to the conditions that the provisions of condition (17) of rule provisions of condition (17) of rule 65 of the Drugs and Cosmetics Rules, 1945 are complied with by the person stocking or selling mechanical contraceptives.]
___________________________________________________________________ 1 Subs. by G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 2 Ins. by G.O.I. Notification No. F.1-39/61-D dt 23.3.1964.
453
Class of Drugs Extent and Conditions of Exemption 1[14A Vaginal contraceptive pessaries
containing Nonoxynol. The provision of Chapter IV of the Act and the Rules made thereunder which require them to be covered by a sale licence subject to the condition that the provisions of clause (17) of the Rule 64 of the Drugs and Cosmetics Rules 1945 are complied with by the person stocking or selling this contraceptive.]
2[15. Chemical contraceptive having the following composition per tablet:-
3[(1) DL-Norgestrel – 0.3 mg] Ethinyloestradiol – 0.03mg
(2) Levonorgestrel – 0.15 mg. Ethinylestraditol – 0.3 mg
(3) Centchroman – 30 mg. 4[(4) Desogestrel -- 0.150 mg.
Ethinyloestradiol – 0.030 mg (5) Levonorgestrel -- 0.1 mg
Ethinyloestradiol - 0.02 mg]
The provision of Chapter IV of the Act and the Rules thereunder which required them to be covered with a sale licence.]
5[16 Cosmetics. The provisions of Chapter IV of the Act and the Rules made thereunder, which require them to be covered by a licence for sale provided that the cosmetics sold, if of Indian origin, are manufactured by licenced manufacturers.]
6[17. Ophthalmic ointments of the Tetracycline group of drugs
Persons authorised by the Government to distribute or sell the drugs under the National Trachoma Control Programme shall be exempted from the provisions of Chapter IV of the Act and the Rules made thereunder, which require the drugs to be covered by a sale licence.
18. [ [Omitted by G.O.I. Notification No. GSR 1594 dt 13.11.1976.]
7[19 Hair Fixers, namely mucilaginous preparations containing gums, used by men for fixing beard.
The provisions of Chapter IV of the Act and the Rules thereunder.]
____________________________________________________________________ 1 Ins, by G.O.I. Notification No. GSR 784(E) dt 28.8.1989. 2 & 3 Subs. by G.O.I. Notification No. GSR 730 (E) dt 10.12.1991 and corrected by GSR 305(E) dt 4.3.1992. 4 Ins. by G.O.I. Notification No. GSR 648(E) dt 16.9.2002. 5 Ins. by G.O.I. Notification No. 1-36/64-D dt 17.8.1964. 6 Ins. by G.O.I. Notification No. I-21/63-D dt 4.1.1965. 7 Ins. by G.O.I. Notification No. S.O.2139 dt 12.8.1971.
454
Class of Drugs Extent and Conditions of Exemption 1 [20 Radio Pharmaceuticals. All the provisions of Chapter IV of the Act, and
the Rules made hereunder.]
2[21 Tablets of Chloroquine Salets. The provisions of Chapter IV of the Act and the Rules thereunder, which require them to be covered by a sale licence, provided the drug in strip pack is sold under the Commercial Distribution Scheme of the National Malaria Eradication Programme and duly labeled as ‘National Malaria Eradication Programme- Ministry of Health and family Welfare, Government of India.
3[22 Sales from restaurant cars of trains and from coastal ships of household remedies, which do not require the supervision of a qualified person for their sale.
The provision of Chapter IV of the Act and the Rules thereunder which require them to be covered with a sale licence, subject to the following conditions, namely:-
(a) the records of purchase and sale of drugs shall be maintained by the person in charge of sale of such drugs, which shall e available for inspection by an Inspector appointed under the Act.
(b) the place where such drugs are stocked be shall be open to inspection by an Inspector appointed under the Act who can, if necessary, take samples for test.]
4[23. Drugs supplied by : (i) Multipurpose Workers attached to Primary Health Centres/Sub-Centres, (ii) Community Health Volunteers under the Rural Health Scheme [5(and)] (iii) Nurses, Auxiliary Nurse, Midwives and Lady Health Visitors attached to Urban Family Welfare Cenres/Primary Health Centre/Sub Centres and 5[(iv) Anganwadi Workers.]
The provision of Chap ter IV of the Act and the Rules thereunder which require them to be covered by a sale licence, provided the drugs are supplied under the Health or Family Welfare Programme of the Central or State Governments.]
____________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 926 dt 16.7.1977. 2Ins. by G.O.I. Notification No. GSR 697(E) dt 11.11.1977. 3 Ins. by G.O.I. Notification No. GSR 124(E) dt 15.9.1979. 4Ins. by G.O.I. Notification No. GSR 540(E) dt 22.9.1980 5Amended by G.O.I. Notifiation No. GSR 784 (E) dt 28.8.1989
455
Class of Drugs Extent and Conditions of Exemption 1[24 Homoeopathic medicines supplied by
a registered Homoeopathic medical practitioner to his own patient or Homoeopathic medicines supplied by a registered Homoeopathic medical practitioner at the request of another such practitioner provided the registered Homoeopathic medical
All the provision of Chapter IV of the Act and the rules made thereunder subject to the following conditions:-
(1) The Homoeopathic medicines shall be purchased only from a dealer or a manufacturer licensed under the Drugs and Cosmetics Rules 1945.
Practitioner is not (a) keeping an open shop, or (b) selling across the counter or, (c) engaged in the im- portation, manufacture, distribution or sale of Homoeopathic medicines in India to a degree which renders him liable to the provisions of Chapter IV of the Act and the rules made thereunder.
(2) The premises where the Homoeopathic medicines are stocked shall be open to inspection by an Inspector appointed under the Act, who may, if necessary, take samples for test.”]
2[25 Preparations applied to human body for the purpose repelling insets like mosquitoes.
The provisions of Chapter IV of the Act and Rules thereunder which require them to be covered by a sale licence subject to conditions that such a product has been manufactured under a valid drug manufacturing licence.
26 3[Medicated Dressing and Bandages for First Aid.]
The provisions of Chapter IV of the Act and Rules thereunder which require them to be covered by a sale licence subject to the conditions that such a product has been manufactured under a valid drug manufacturing licence.]
4[27 Oral Rehydration Salts (Manufactured as per the following formula) :
Sodium chloride 3.5 g/litre * Trisodium citrate dihydrate 2.9
g/litre. Potassium Chloride 1.5 g/litre
*May be replaced by Sodium bicarbonate (Sodium hydrogen Carbonate) 2.5 g/litre, when citrate salt is not available.
The provision of Chapter IV of the Act and Rules thereunder which required them to be covered by a sale licence, subject to the conditions that such a product has been manufactured under a valid drug manufacturing Licence.]
______________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 680(E) dt 5.12.1980. 2Ins. by G.O.I. Notification No. GSR 1060(E) dt 5.9.1986. 3Sub. By G.O.I. Notification No. GSR 371(E) dt 24.3.1988. 4Ins. by G.O.I. Notification No. GSR 677(E) dt 2.6.1988.
456
Class of Drugs Extent and Conditions of Exemption 1[28 White or Yellow Petroleum Jelly
I.P. (Non perfumed). The provision of Chapter IV of the Act and the rules made thereunder which require them to be covered by a sale licence, subject to the condition that such a product has been manufactured under a valid drug manufacturing licence.]
2[29 Morphine tablets The provision of Chapter IV of the Act and the rules made thereunder which require them to be covered by a sale licence, subject to the following conditions, namely:-
(i) The drug shall be supplied by the Palliative Care Centre approved by the State Government to terminally ill cancer patients.
(ii) The drug shall be purchased from a dealer or a manufacturer who holds licence under these rules, and records of such purchases showing the names and quantities together with their batch numbers, and name and addresses of the manufacturers or dealers and the name and address of the patients to whom supplies have been mad e shall be maintained. Such records shall be open to inspection by Inspection appointed under the Act, who may also take samples for test.
30 Whole Human Blood collected and transfused by Centres run by Armed Forces Medical Services in border areas, small mid -zonal hospitals including peripheral hospitals, Field Ambulances, Mobile medical units and other field medical units including blood supply units in border, sensitive and field areas.
(i)
All the provisions of Chapter IV of the Act and rules made thereunder which require them to be covered by a licence to operate a Blood Bank for collection, storage and processing of whole human blood for sale or distribution subject to the following conditions-
These Centres shall collect, process and transfuse blood in emergent situations which require life saving emergency surgeries/or transfusion.
____________________________________________________________________________ 1 Ins.by G.O.I. Notification No.GSR 753(E) dt 4.11.1999. 2 Ins. by G.O.I. Notification No. GSR 6(E) dt 4.1.2001
457
Class of Drugs Extent and Conditions of Exemption (ii) These Centres shall be under the active direction
and personal supervision of a qualified Medical Officer, possessing the qualifications and experiences specified in condition (i) of rule 122- G.
(iii) Each blood unit shall be tested before for freedom from HIV I and II antibodies, Hepatitis B surface antigen, malarial parasites and other tests specified under the monograph “Whole Human Blood” in current edition of Indian Pharmacopoeia.
(iv) These Centres shall have adequate infrastructure facilities for storage and transportation of blood.
(v) The blood collected and tested by such Centres shall be transfused by the Centre itself and may be made available for use of other peripheral Armed Forces hospitals or centers during operational circumstances.]
1[31 .
The following Homoeo - pathic Medicines, namely:- a) Arnica Montana Hair
Oil b) Homeopathic ointments,
each in 15 gm. Tube:
The provisions of Chapter IV of the Act and the Rules made thereunder which require them to be covered with a sale licence in form 20-C subject to the following conditions:-
i) ii) iii)
Arnica Montana Calendula Officinalis Cantharis
(i) These homoeopathic medicines shall be sold in the original sealed small quantity packings of the licensed manufacturers.
iv) Rhus Toxicodendron (ii)
These medicines may be stocked and sold by retail dealers of medicines licensed under Rule 61.
________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 218(E) dt 28.3.2001.
458
Class of Drugs Extent and Conditions of Exemption c) Biochemic tissue remedies in
tablets forms, in generic names only, each in 20 gm. Packing in 3x and 6x trituration :
(iii)
(iv)
These medicines shall be stored separately from other allopathic drugs.
These medicines shall be purchased from a
i) ii)
Calcarea Phosphorica Calcarea Sulphurica
manufacturer or a dealer licensed under these Rules.
iii) iv) v)
Ferum Phosphoricum Kali Muriaticum Kali Phosphoricum
(v) The purchase and sale records of these medicines shall be maintained by the dealer for a minimum period of three years.
vi) vii)
Kali Sulphuricum Magnesium Phosphoricum
(vi) These medicines shall be labeled in generic/pharmacopoeial names only.]
viii) Megnesia Sulphurica ix) Natrum Muriaticum x) Natrum Phosphoricum xi) Natrum Sulphuricum xii) Silicea
d) Homoeopathic medicines, mentioned below, in pills, each in 30 C potency, in sealed original packing of manufacturer of 8 gms.
i) Armica Montana ii) Aconitum Napellus iii) Arsenicum Album iv) Aloe Socotrina v) Apis Mellifica vi) Allium Cepa vii) Bryonia alba viii) Borax ix) Belladonna x) Cantharis xi) Carbo Vegetabilis xii) Cina xiii) Colocynthis xiv) Calendula Officinalis xv) Caulophyllum Thalictroides xvi) Cocculus Indicus xviii) Drosera Rotundifolia xix) Hypericum Perforatum xx) Hepar Sulphur xxi) Ipecacuanha xxii) Ledum Palustre
459
[*32 First Aid Kit supplied along with
motor vehicle by the
manufacturer or its distributor at
the time of first sale of vehicle.
The provisions of Chapter IV of the Act and rules made there under which require them to be covered by a sale licence, subject to the condition that the drug items are procured from a manufacturer or dealer licensed under the rules.]
*Ins. by G.O.I.Notification no. G.S.R. 648 (E) dt 16.09.2002.
xxiii) Millefolium xxiv) Mercurius Solubillis xxv) Nux Vomica xxvi) Pulsatilla Nigricans xxvii) Podophyyllum
Peltatum xxviii) Plantago Major xxix) Rhus Toxicodendron xxx) Ruta Grveolens xxxi) Symphytum Officinalis xxxii) Veratrum Album
460
SCHEDULE L
[see Rules 65(9) and 97] ? [Omitted]
?? [SCHEDULE M
[See Rules 71, 74, 76 and 78]
GOOD MANUFACTURING PRACTICES AND REQUIREMENTS OF PREMISES, PLANT AND EQUIPMENT FOR PHARMACEUTICAL PRODUCTS.
Note: - To achieve the objectives listed below, each licensee shall evolve appropriate methodology, systems and procedures which shall be documented and maintained for inspection and reference; and the manufacturing premises shall be used exclusively for production of drugs and no other manufacturing activity shall be undertaken therein.
PART 1
GOOD MANUFACTURING PRACTICES FOR PREMISES AND MATERIALS.
(1) GENERAL REQUIREMENTS
(A) Location and surroundings.- The factory building(s) for manufacture of drugs shall be so situated and shall have such measures as to avoid risk of contamination from external environmental including open sewage, drain, public lavatory or any factory which product disagreeable or obnoxious odour, fumes, excessive soot, dust, smoke, chemical or biological emissions.
(B)Building and premises.- The building(s) used for the factory shall be designed, constructed, adapted and maintained to suit the manufacturing operations so as to permit production of drugs under hygienic conditions. They shall conform to the conditions laid down in the Factories Act, 1948 (63 of 1948)
The premises used for manufacturing, processing, warehousing, packaging labeling and testing purposes shall be – _________________________________________________________________________ ? Omitted by G.O.I.Notification No.G.S.R.462(E) dt.22.06.1982. ??Ins.by G.O.I.Notification NoG.S.R.864(E) dt.11.12.2001.- applicable to manufacturers licensed to manufacture drugs, for the period upto 31.12.2003.
461
(i) compatible with other drug manufacturing operations that may be carried out in the same or adjacent area / section;
(ii) adequately provided with working space to allow orderly and logical placement of equipment, materials and movement of personnel so as to:
(a) avoid the risk of mix-up between different categories of drugs or with raw materials, intermediates and in-process material;
(b) avoid the possibilities of contamination and cross- contamination by providing suitable mechanism;
(iii) designed / constructed / maintained to prevent entry of insects, pests, birds, vermins, and rodents. Interior surface (walls, floors and ceilings) shall be smooth and free from cracks, and permit easy cleaning, painting and disinfection;
(iv) air-conditioned, where prescribed for the operations and dosage froms under production. The production and dispensing areas shall be well lighted, effectively ventilated, with air control facilities and may have proper Air Handling Units (wherever applicable) to maintain conditions including temperature and, wherever necessary, humidity, as defined for the relevant product. These conditions shall be appropriate to the category of drugs and nature of the operation. These shall also be suitable to the comforts of the personnel working with protective clothing, products handled, operations undertaken within them in relation to the external environment. These areas shall be regularly monitored for compliance with required specifications;
(v) Provided with drainage system, as specified for the various categories of products, which shall be of adequate size and so designed as to prevent back flow and/or prevent insets and rodents entering the premises. Open channels shall be avoided in manufacturing areas and, where provided, these shall be shallow to facilitate cleaning and disinfection;
(vi) The walls and floors of the areas where manufacture of drugs is carried out shall be free from cracks and open joints to avoid accumulation of dust. These shall be smooth, washable, covered and shall permit easy and effective cleaning and dis-infection. The interior surfaces shall not shed particles. A periodical record of cleaning and painting of the premises shall be maintained.
462
(C ) Water Supply. - There shall be validated system for treatment of water drawn from own or any other source to render it potable in accordance with standards specified by the Bureau of Indian Standards or Local Municipality, as the case may be, so as to produce Purified Water conforming to Pharmacopoeial specification. Purified Water so produced shall only be used for all operations except washing and cleaning operations where potable water may be used. Water shall be stored in tanks, which do not adversely affect quality of water and ensure freedom from microbiological growth. The tank shall be cleaned periodically and records maintained by the licensee in this behalf.
(D)Disposal of waste. -
(i) The disposal of sewage and effluents (solid, liquid and gas) from the manufactory shall be in conformity with the requirements of Environment Pollution Control Board.
(ii) All bio-medical waste shall be destroyed as per the provisions of the Bio-Medical Waste (Management and Handling) Rules, 1996.
(iii)Additional precautions shall be taken for the storage and disposal of rejected drugs. Records shall be maintained for all disposal of waste.
(iv)Provisions shall be made for the proper and safe storage of waste materials awaiting disposal. Hazardous,toxic substances and flammable materials shall be stored in suitably designed and segregated, enclosed areas in conformity with Central and State Legislations.
(2) Warehousing Area. -
2.1 Adequate areas shall be designed to allow sufficient and orderly warehousing of various categories of materials and products like starting and packaging materials, intermediates, bulk and finished products, products in quarantine, released, rejected, returned or recalled, machine and equipment spare parts and change items.
2.2 Warehousing areas shall be designed and adapted to ensure good storage conditions. They shall be clean, dry and maintained with acceptable temperature limits, where special storage conditions are required (e.g. temperature, humidity), these shall be provided, monitored and recorded. Storage areas shall have appropriate house-keeping and rodent, pests and vermin control procedures and records maintained. Proper racks, bins and platforms shall be provided for the storage of materials.
2.3 Receiving and dispatch bays shall protect materials and products from adverse weather conditions.
2.4 Where quarantine status is ensured by warehousing in separate earmarked areas in the same warehouse or store, these areas shall be clearly demarcated. Any system replacing the
463
physical quarantine, shall give equivalent assurance of segregation. Access to these areas shall be restricted to authorized persons.
2.4.There shall be a separate sampling area in the warehousing area for active raw materials and excipients. If sampling is performed in any other area, it shall be conducted in such a way as to prevent contamination, cross-contamination and mix-up.
2.5.Segregation shall be provided for the storage of rejected, recalled or returned materials or products. Such areas, materials or products shall be suitably marked and secured. Access to these areas and materials shall be restricted.
2.6.Highly hazardous, poisonous and explosive materials such as narcotics, psychotropic drugs and substances presenting potential risks of abuse, fire or explosion shall be stored in safe and secure areas. Adequate fire protection measures shall be provided in conformity with the rules of the concerned civic authority.
2.7.Printed packaging materials shall be stored in safe, separate and secure areas.
2.8.Separate dispensing areas for ß (Beta) lactum, Sex Hormones and Cytotoxic substances or any such special categories of product shall be provided with proper supply of filtered air and suitable measures for dust control to avoid contamination. Such areas shall be under differential pressure.
2.9.Sampling and dispensing of sterile materials shall be conducted under aseptic conditions conforming to Grade A, which can also be performed in a dedicated area within the manufacturing facility.
2.10. Regular checks shall be made to ensure adequate steps are taken against spillage, breakage and leakage of containers.
2.11. Rodent treatments (Pest control) should be done regularly and at least once in a year and record maintained.
(3) Production area. -
3.1. The production area shall be designed to allow the production preferably in uni-flow and with logical sequence of operations.
3.2. In order to avoid the risk of corss-contamination, separate dedicated and self- contained facilities shall be made available for the production of sensitive pharmaceutical products like penicillin or biological preparations with live micro-organisms. Separate dedicated facilities shall be provided for the manufacture of contamination causing and potent products such as Beta-Lactum, sex hormones and cytotoxic substances.
464
3.3. Working and in-process space shall be adequate to permit orderly and logical positioning of equipment and materials and movement of personnel to avoid cross- contamination and to minimize risk of omission or wrong application of any manufacturing and control measures.
3.4. Pipe-work, electrical fittings, ventilation openings and similar services lines shall be designed, fixed and constructed to avoid creation of recesses. Services lines shall preferably be identified by colours and the nature of the supply and direction of the flow shall be marked/indicated.
(4.) Ancillary Areas. -
4.1 Rest and refreshment rooms shall be separate from other areas. These areas shall not lead directly to the manufacturing and storage areas.
4.2 Facilities for changing, storing clothes and for washing and toilet purposes shall be easily accessible and adequate for the number of users. Toilets, separate for males and females, shall not be directly connected with production or storage areas. There shall be written instructions for cleaning and disinfection of such areas.
4.3 Maintenance workshops shall be separate and away from production areas. Whenever spares, changed parts and tools are stored in the production area, these shall be kept in dedicated rooms or lockers. Tools and spare parts for use in sterile areas shall be disinfected before these are carried inside the production areas.
4.4. Areas housing animals shall be isolated from other areas. The other requirements regarding animal houses shall be those as prescribed in Rule 150-C(3) of the Drugs and Cosmetics Rules, 1945 which shall be adopted for production purposes.
(5.)Quality Control Area.-
5.1. Quality Control Laboratories shall be independent of the production areas. Separate areas shall be provided each for physico-chemical, biological, microbiological or radio- isotope analysis. Separate instrument room with adequate area shall be provided for sensitive and sophisticated instruments employed for analysis.
5.2 Quality Control Laboratories shall be designed appropriately for the operations to be carried out in them. Adequate space shall be provided to avoid mix-ups and cross- contamination. Sufficient and suitable storage space shall be provided for test samples, retained samples, reference standards, reagents and records.
465
5.3. The design of the laboratory shall take into account the suitability of construction materials and ventilation. Separate air handling units and other requirements shall be provided for biological, microbiological and radioisotopes testing areas. The laboratory shall be provided with regular supply of water of appropriate quality for cleaning and testing purpose.
5.4. Quality Control Laboratory shall be divided into separate sections i.e. for chemical, microbiological and wherever required, biological testing. These shall have adequate area for basis installation and for ancillary purposes. The microbiology section shall have arrangements such as airlocks and laminar air flow work station, wherever considered necessary.
(6.) Personnel.-
6.1. The manufacture shall be conducted under the direct supervision of competent technical staff with prescribed qualifications and practical experience in the relevant dosage and / or active pharmaceutical products.
6.2 The head of the Quality Control Laboratory shall be independent of the manufacturing unit. The testing shall be conducted under the direct supervision of competent technical staff who shall be whole time employees of the licensee.
6.3. Personnel for Quality Assurance and Quality Control operations shall be suitably qualified and experienced.
6.4. Written duties of technical and Quality Control personnel shall be laid and following strictly.
6.5. Number of personnel employed shall be adequate and in direct proportion to the workload.
6.6. The licensee shall ensure in accordance with a written instruction that all personnel in production area or into Quality Control Laboratories shall receive training appropriate to the duties and responsibility assigned to them. They shall be provided with regular in-service training.
(7.) Health, clothing and sanitation of workers. -
7.1 The personnel handling Beta-lactum antibiotics shall be tested for Penicillin sensitivity before employment and those handling sex hormones, cytotoxic substances and other potent drugs shall be periodically examined for adverse effects. These personnel should be moved out of these sections (except in dedicated facilities), by rotation, as a health safeguard.
466
7.2 Prior to employment, all personnel, shall undergo medical examination including eye examination, and shall be free from Tuberculosis, skin and other communicable or contagious diseases. Thereafter, they should be medically examined periodically, at least once a year. Records shall be maintained thereof. The licensee shall provide the services of a qualified physician for assessing the health status of personnel involved in different activities.
7.3 All persons prior to and during employment shall be trained in practices which ensure personnel hygiene. A high level of personal hygiene shall be observed by all those engaged in the manufacturing processes. Instructions to this effect shall be displayed in change rooms and other strategic locations.
7.4 No person showing, at any time, apparent illness or open lesions which may adversely affect the quality of products, shall be allowed to handle starting materials, packing materials, in-process materials, and drug products until his condition is no longer judged to be a risk.
7.5 All employees shall be instructed to report about their illness or abnormal health condition to their immediate supervisor so that appropriate action can be taken.
7.6 Direct contact shall be avoided between the unprotected hands of personnel and raw materials, intermediate or finished, unpacked products.
7.7 All personnel shall wear clean body coverings appropriate to their duties. Before entry into the manufacturing area, there shall be change rooms separate for each sex with adequate facilities for personal cleanliness such as wash basin with running water, clean towels, hand dryers, soaps, disinfectants, etc. The change room shall be provided with cabinets for the storage of personal belongings of the personnel.
7.8 Smoking, eating, drinking, chewing or keeping plants, food, drink and personal medicines shall not be permitted in production, laboratory, storage and other areas where they might adversely influence the product quality.
(8.) Manufacturing Operations and Controls. -
8.1 All manufacturing operations shall be carried out under the supervision of technical staff approved by the Licensing Authority. Each critical step in the process relating to the selection, weighing and measuring of raw material addition during various stages shall be performed by trained personnel under the direct personal supervision of approved technical staff.
The contents of all vessels and containers used in manufacture and storage during the various manufacturing stages shall be conspicuously labeled with the name of the product, batch number, batch size and stage of manufacture. Each label should be initialled and dated by the auhorised technical staff.
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Products not prepared under aseptic conditions are required to be free from pathogens like Salmonella, Escherichia coli, Pyocyanea, etc.
8.2. Precautions against mix-up and cross-contamination-
8.2.1. The licensee shall prevent mix-up and cross-contamination of drug material and drug product (from environmental dust) by proper air-handling system, pressure differential, segregation, status labeling and cleaning. Proper records and Standard Operating Procedures thereof shall be maintained.
8.2.2 The licensee shall ensure processing of sensitive drugs like Beta-Lactum antibiotics, sex hormones and cytotoxic substances in segregated areas or isolated production areas within the building with independent air-handling unit and proper pressure differential. The effective segregation of these areas shall be demonstrated with adequate records of maintenance and services.
8.2.3 To prevent mix-ups during production stages, materials under process shall be conspicuously labeled to demonstrate their status. All equipment used for production shall be labeled with their current status.
8.2.4 Packaging lines shall be independent and adequately segregated. It shall be ensured tat all left-overs of the previous packaging operations, including labels, cartons and caps are cleared before the closing hour.
8.2.5 Before packaging operations are begun, steps shall be taken to ensure that the work area, packaging lines, printing machines, and other equipment are clean and free from any products, materials and spillages. The line clearance shall be performed according to an approximate check-list and recorded.
8.2.6 The correct details of any printing (for example of batch numbers or expiry dates) done separately or in the course of the packaging shall be rechecked at regular intervals. All printing and overprinting shall be authorized in writing.
8.2.7 The manufacturing environment shall be maintained at the required levels of temperature, humidity and cleanliness.
8.2.8 Authorised persons shall ensure change-over into specific uniforms before undertaking any manufacturing operations including packaging.
8.2.9 There shall be segregated enclosed areas, secured for recalled or rejected material and for such materials which are to e reprocessed or recovered.
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(9.)Sanitation in the Manufacturing Premises. -
9.1 The manufacturing premises shall be cleaned and maintained in an orderly manner, so that it is free from accumulated waste, dust, debris and other similar material. A validated cleaning procedure shall be maintained.
9.2 The manufacturing areas shall not be used for storage of materials, except for the material being processed. It shall not be used as a general throughfare.
9.3 A routine sanitation program shall be drawn up and observed, which shall be properly recorded and which shall indicate--
(a) specific areas to be cleaned and cleaning intervals; (b) cleaning procedure to be followed, including equipment and materials to be used
for cleaning; and (c) personnel assigned to and responsible for the cleaning operation.
9.4 The adequacy of the working and in-process storage space shall permit the orderly and logical positioning of equipment and materials so as to minimize the risk of mix-up between different pharmaceutical products or their components to avoid cross contamination, and to minimise the risk of omission or wrong application of any of the manufacturing or control steps.
9.5 Production areas shall be well lit, particularly where visual on-line controls are carried out.
(10.) Raw Materials. -
10.1 The licensee shall keep an inventory of all raw materials to be used at any stage of manufacture of drugs and maintain records as per Schedule U.
10.2 All incoming materials shall be quarantined immediately after receipt or processing. All materials shall be stored under appropriate conditions and in an orderly fashion to permit batch segregation and stock rotation by a ‘first in/first expiry’ – ‘first-out’ principle. All incoming materials shall be checked to ensure that the consignment corresponds to the order placed.
10.3 All incoming materials shall be purchased from approved sources under valid purchase vouchers. Wherever possible, raw materials should be purchased directly from the producers.
10.4 Authorized staff appointed by the licensee in this behalf, which may include personnel from the Quality Control Department, shall examine each consignment on receipt
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and shall check each container for integrity of package and seal. Damaged containers shall be identified, recorded and segregated.
10.5 If a single delivery of material is made up of different batches, each batch shall be considered as a separate batch for sampling, testing and release.
10.6 Raw materials in the storage area shall be appropriately labeled. Labels shall be clearly marked with the following information:
(a) designated name of the product and the internal code reference, where applicable, and analytical reference number;
(b) manufacturer’s name, address and batch number; (c) the status of the contents (e.g. quarantine, under test, released,
approved, rejected); and (d) the manufacturing date, expiry date and re-test date.
10.7 There shall be adequate separate areas for materials “under test”, “approved” and “rejected” with arrangements and equipment to allow dry, clean and orderly placement of stored materials and products, wherever necessary, under controlled temperature and humidity.
10.8 Containers from which samples have been drawn shall be identified.
10.9 Only raw materials which have been released by the Quality Control Department and which are within their shelf-life shall be used. It shall be ensured that shelf life of formulation product shall not exceed with that of active raw materials used.
10.10 It shall be ensured that all the containers of raw materials are placed on the raised platforms/racks and not placed directly on the floor.
(11.) Equipment. -
11.1 Equipment shall be located, designed, constructed, adapted and maintained to suit the operations to be carried out. The layout and design of the equipment shall aim to minimise the risk of errors and permit effective cleaning and maintenance in order to avoid cross- contamination, build-up of dust or dirt and, in general any adverse effect on the quality of products. Each equipment shall be provided with a logbook, wherever necessary.
11.2 Balances and other measuring equipment of an appropriate range, accuracy and precision shall be available in the raw material stores, production and in process control operations and these shall be calibrated and checked on a scheduled basis in accordance with Standard Operating Procedures and records maintained.
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11.3 The parts of the production equipment that come into contact with the product shall not be reactive, additive or adsorptive to an extent that would affect the quality of the product.
11.4 To avoid accidental contamination, wherever possible, non-toxic/edible grade lubricants shall be used and the equipment shall be maintained in a way that lubricants do not contaminate the products being produced.
11.5 Defective equipment shall be removed from production and Quality Control areas or appropriately labeled.
12. Documentation and Records. - Documentation is an essential part of the Quality assurance system and, as such, shall be related to all aspects Good Manufacturing Practices (GMP). Its aim is to define the specifications for all materials, method of manufacture and control, to ensure that all personnel concerned with manufacture know the information necessary to decide whether or not to release a bath of drug for sale and to provide an audit trail that shall permit investigation of the history of any suspected defective batch.
12.1 Documents designed, prepared, reviewed and controlled, wherever applicable, shall comply with these rules.
12.2 Documents shall be approved, signed and dated by appropriate and authorized persons.
12.3 Documents shall specify the title, nature and purpose. They shall be laid out in an orderly fashion and be easy to check. Reproduced documents shall be clear and legible. Documents shall be regularly reviewed and kept up to date. Any alteration made in the entry of a document shall be signed and dated.
12.4 The records shall be made or completed at the time of each operation in such a way that all significant activities concerning the manufacture of pharmaceutical products are traceable. Records and associated Standard Operating Procedures (SOP) shall be retained for at least one year after the expiry date of the finished product.
12.5 Data may be recorded by electronic data processing systems or other reliable means, but Master Formulae and detailed operating procedures relating to the system in use shall also be available in a hard copy to facilitate checking of the accuracy of the records. Wherever documentation is handled by electronic data processing methods, authorized persons shall enter modify data in the computer. There shall be record of changed and deletions. Access shall be restricted by ‘passwords’ or other means and the result of entry of critical data shall be independently checked. Batch records electronically stored shall be protected by a suitable back-up. During the period of retention, all relevant data shall be readily available.
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13. Labels and other Printed Materials. - Labels are absolutely necessary for identification of the drugs and their use. The Printing shall be done in bright colours and in a legible manner. The label shall carry all the prescribed details about the product.
13.1 All containers and equipment shall bear appropriate labels. Different colour coded tablets shall be used to indicate the status of a product (for example under test, approved, passed, rejected).
13.2 To avoid chance mix-up of printed packaging materials, product leaflets, relating to different products, shall be stored separately.
13.3 Prior to release, all labels for containers, cartons and boxes and all circulars, inserts and leaflets shall be examined by the Quality Control Department of the licensee.
13.4 Prior to packaging and labeling of a given batch of a drug, it shall be ensured by the licensee that samples are drawn from the bulk and duly tested, approved and released y the quality control personnel.
13.5 Records of receipt of all labeling and packaging materials shall be maintained for each shipment received indicating receipt, control reference numbers and whether accepted or rejected. Unused coded and damaged labels and packaging materials shall be destroyed and recorded.
13.6 The label or accompanying document of reference standards and reference culture shall indicate concentration, lot number, potency, date on which containers was first opened and storage conditions, where appropriate.
14. Quality Assurance. - This is a wide-ranging concept concerning all matters that individually or collectively influence the quality of a product. It is the totality of the arrangements made with the object of ensuring that products are of the quality required for their intended use.
14.1 The system of quality assurance appropriate to the manufacture of pharmaceutical products shall ensure that: -
(a) the pharmaceutical products are designed and developed in a way that takes account of the requirement of Good Manufacturing Practices (herein referred as GMP) and other associated codes such as those of Good Laboratory Practices (hereinafter referred as GLP) and Good Clinical Practices (herein after referred as GCP);
(b) adequate arrangements are made for manufacture, supply and use of the correct starting and packaging materials.
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(c) adequate controls on starting materials, intermediate products, and bulk products and other in-process controls, calibrations, and validations are carried out.
(d) the finished product is correctly processed and checked in accordance with established procedures;
(e) the pharmaceutical products are not released for sale or supplied before authorized persons have certified that each production batch as been produced and controlled in accordance with the requirements of the label claim and any other provisions relevant to production, control and release of pharmaceutical products.
(15.) Self Inspection and Quality audit - It may be useful to constitute a self-inspection team supplemented with a quality audit procedure for assessment of all or part of a system with the specific purpose of improving it.
15.1 To evaluate the manufacturer’s compliance with GMP in all aspects of production and quality control, concept of self-inspection shall be followed. The manufacturer shall constitute a team of independent, experienced, qualified persons from within or outside the company, who can audit objectively the implementation of methodology and procedures evolved. The procedure for self-inspection shall be documented indicating self-inspection results; evaluation, conclusions and recommended corrective actions with effective follow up program. The recommendations for corrective action shall be adopted.
15.2 The program shall be designed to detect shortcomings in the implementation of Good Manufacturing Practice and to recommend the necessary corrective actions. Self- inspections shall be performed routinely and on specific occasions, like when product recalls or repeated rejections occur or when an inspection by the licensing authorities is announced. The team responsible for self-inspection shall consist of personnel who can evaluate the implementation of Good Manufacturing Practice objectively; all recommendations for corrective action shall be implemented.
15.3 Written instructions for self-inspection shall be drawn up which shall include the following: -
(a) Personnel (b) Premises including personnel facilities. (c) Maintenance of buildings and equipment (d) Storage of starting materials and finished products (e) Equipment (f) Production and in-process controls (g) Quality control
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(h) Documentation (i) Sanitation and hygiene (j) Validation and revalidation programmes (k) Calibration of instruments or measurement systems. (l) Recall procedures (m) Complaints management (n) Labels control (o) Results of previous self-inspections and any corrective steps taken.
(16.) Quality Control System. - Quality control shall be concerned with sampling, specifications, testing, documentation, release procedures which ensure that the necessary and relevant tests are actually carried and that the materials are not released for use, nor products released for sale or supply until their quality has been judged to be satisfactory. It is not confined to laboratory operations but shall be involved n all decisions concerning the quality of the product. It shall be ensured that all quality control arrangements are effectively and reliably carried out the department as a whole shall have other duties such as to establish evaluate, validate and implement all Quality Control Procedures and methods.
16.1 Every manufacturing establishment shall establish its own quality control laboratory manner by qualified and experience staff.
16.2 The area of the quality control laboratory may be divided into Chemical, Instrumentation, Microbiological and Biological testing.
16.3 Adequate area having the required storage conditions shall be provided for keeping reference samples. The quality control department shall evaluate, maintain and store reference samples.
16.4 Standard operating procedures shall be available for sampling, inspecting and testing of raw materials, intermediate bulk finished products and packing materials and, wherever necessary, for monitoring environmental conditions.
16.5 There shall be authorized and dated specifications for all materials, products, reagents and solvents including test of identity, content, purity and quality. These shall include specifications for water, solvents and reagents used in analysis.
16.6 No batch of the product shall be released for sale or supply until it has been certified by the authorized person(s) that it is in accordance with the requirements of the standards laid down.
16.7 Reference/retained samples from each batch of the products manufactured shall be maintained in quantity which is at least twice the quantity of the drug required to conduct all the tests, except sterility and pyrogen/Bacterial Endotoxin Test performed on the active
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material and the product manufactured. The retained product shall be kept in its final pack or simulated pack for a period of three months after the date of expiry.
16.8 Assessment of records pertaining to finished products shall include all relevant factors, including the production conditions, the results of in process testing, the manufacturing (including packaging) documentation, compliance with the specification for the finished product, and an examination of the finished pack. Assessment records should be signed by the in-charge of production and countersigned by the authorised quality control personnel before a product is released for sale or distribution.
16.9 Quality control personnel shall have access to production areas for sampling and investigation, as appropriate.
16.10 The quality control department shall conduct stability studies of the products to ensure and assign their shell life at the prescribed conditions of storage. All records of such studies shall be maintained.
16.11 The in-charge of Quality Assurance shall investigate all product complaints and records thereof shall be maintained.
16.12 All instruments shall be calibrated and testing procedures validated before these are adopted for routine testing. Periodical calibration of instrument and validation of procedures shall be carried out.
16.13 Each specification for raw materials, intermediates, final products, and packing materials shall be approved and maintained by the Quality Control Department. Periodic revisions of the specifications shall be carried out wherever changes are necessary.
16.14 Pharmacopoeiae, reference standards, working standards, references, spectra, other reference materials and technical books, as required, shall be available in the Quality Control Laboratory of the licensee.
17. Specification
17.1 For raw materials and packaging materials. - They shall include-
a) the designated name and internal code reference; b) reference, if any, to a pharmacopoeial monograph; c) qualitative and quantitative requirements with acceptance limits; d) name and address of manufacturer or supplier and original manufacturer of
the material; e) specimen of printed material; f) directions for sampling and testing or reference to procedures;
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g) storage conditions; and h) maximum period of storage before re-testing.
17.2 For product containers and closures. -
17.2.1 all containers and closures intended for use shall comply with the pharmacopoeial requirements. Suitable validated test methods, sample sizes, specifications, cleaning procedure and sterilization procedure, wherever indicated, shall be strictly followed to ensure that these are not reactive, additive, absorptive, or leach to an extent that significantly affects the quality or purity of the drug. No second hand or used containers and closures shall be used.
17.2.2 whenever bottles are being used, the written schedule of cleaning shall be laid down and followed. Where bottles are not dried after washing, they should be rinsed with de- ionised water or distilled water, as the case may be.
17.3.For in-process and bulk products. - Specifications for in-process material, intermediate and bulk products shall be available. The specifications should be authenticated.
17.4 For finished products. - Appropriate specifications for finished products shall include:
a) the designated name of the product and the code reference; b) the formula or a reference to the formula and the pharmacopoeial reference; c) directions for sampling and testing or a reference to procedures; d) a description of the dosage form and package details; e) the qualitative and quantitative requirements, with the acceptance limits for
release; f) the storage conditions and precautions, where applicable, and g) the shelf-life.
17.5 For preparation of containers and closures. - The requirements mentioned in the Schedule do not include requirements of machinery, equipments and premises required for preparation of containers and closures for different dosage forms and categories of drugs. The suitability and adequacy of the machinery, equipment and premises shall be examined taking into consideration the requirements of each licensee in this respect.
(18.) Master Formula Records.
There shall be Master Formula records relating to all manufacturing procedures for each product and batch size to be manufactured. These shall be prepared and endorsed by the
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competent technical staff i.e. head of production and quality control. The master Formula shall include: -
(a) the name of the product together with product reference code relating to its specifications;
(b) the patent or proprietary name of the product along with the generic name, a description of the dosage form, strength, composition of the product and batch size;
(c) name, quantity, and reference number of all the starting materials to be used. Mention shall be made of any substance that may ‘disappear’ in the courts of processing.
(d) a statement of the expected final yield with the acceptable limits, and of relevant intermediate yields, where applicable.
(e) a statement of the processing location and the principal equipment to be used. (f) the methods, or reference to the methods, to be used for preparing the critical
equipments including cleaning, assembling, calibrating, sterilizing. (g) detailed stepwise processing instructions and the time taken for each step; (h) the instructions for in-process control with their limits; (i) the requirements for storage conditions of the products, including the
container, labeling and special storage conditions where applicable; (j) any special precautions to be observed; and (k) packing details and specimen labels.
-(19.) Packing Records. -
There shall be authorised packaging instructions for each product, pack size and type. These shall include or have a reference to the following: -
(a) name of the product; (b) description of the dosage form, strength and composition; (c) the pack size expressed in terms of the number of doses, weight or volume of
the product in the final container; (d) complete list of all the packaging materials required for a standard batch size,
including quantities, sizes and types with the code of reference number relating to the specifications of each packaging material.
(e) reproduction of the relevant printed packaging materials and specimens indicating where batch number and expiry date of the product have been applied;
(f) special precautions to be observed, including a careful examination of the area and equipment in order to ascertain the line clearance before the operations begin.
(g) description of the packaging operation, including any significant subsidiary operations and equipment to be used;
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(h) details of in-process controls with instructions for sampling and acceptance; and
(i) upon completion of the packing and labeling operation, a reconciliation shall be made between number of labeling and packaging units issued, number of units labeled, packed and excess returned or destroyed. Any significant or unusual discrepancy in the numbers shall be carefully investigated before releasing the final batch.
20. Batch Packaging Records.
20.1 A batch packaging record shall be kept for each batch or part batch processed. It shall be based on the relevant parts of the packaging instructions, and the method of preparation of such records shall be designed to avoid transcription errors.
20.2 Before any packaging operation begins, check shall be made and recorded that the equipment and the work stations are clear of the previous products, documents or materials not required for the planned packaging operations, and that the equipment is clean and suitable for use.
21. Batch Processing Records
21.1 There shall be Batch Processing Record for each product. It shall be based on the relevant parts of the currently approved Master Formula. The method of preparation of such records included in the Master Formula shall be designed to avoid transcription errors.
21.2 Before any processing begins, check shall be performed and recorded to ensure that the equipment and work station are clear of previous products, documents or materials not required for the planned process are removed and the equipment is clean and suitable for use.
21.3 During processing, the following information shall be recorded at the time each action is taken and the record shall be dated and signed by the person responsible for the processing operations: -
(a) the name of the product (b) the number of the batch being manufactured, (c) dates and time of commencement, of significant intermediate stages and of
completion of production, (d) initials of the operator of different significant steps of production and where
appropriate, of the person who checked each of these operations, (e) the batch number and/or analytical control number as well as the quantities of
each starting material actually weighed, (f) any relevant processing operation or event and major equipment used, (g) a record of the in-process controls and the initials of the person(s) carrying
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them out, and the results obtained, (h) the amount of product obtained after different and critical stages of
manufacture (yield), (i) comments or explanations for significant deviations from the expected yield
limits shall be given. (j) notes on special problems including details, with signed authorization, for any
deviation from the Master Formula. (k) addition of any recovered or reprocessed material with reference to recovery
or reprocessing stages,
22. Standard Operating Procedures (SOPs) and Records, regarding. -
22.1 Receipt of materials:
22.1.1 there shall be written Standard Operating Procedures and records for the receipt of each delivery of raw, primary and printed packaging material.
22.1.2 the records of the receipts shall include; (a) the name of the material on the delivery note and the number of
containers; (b) the date of receipt; (c) the manufacturer’s and/ or supplier’s name; (d) the manufacturer’s batch or reference number; (e) the total quantity, and number of containers, quantity in each container
received; (f) the control reference number assigned after receipt; (g) any other relevant comment or information.
22.1.3 There shall be written standard operating procedures for the internal labeling, quarantine and storage of starting materials, packaging materials and other materials, as appropriate.
22.1.3 There shall be written standard operating procedures for the internal labeling, quarantine and storage of starting materials, packaging materials and other materials, as appropriate.
22.1.4 There shall be Standard Operating Procedures available for each instrument and equipment and these shall be placed in close proximity to the related instrument and equipment.
22.2 Sampling: -
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22.2.1 There shall be written Standard Operating Procedures for sampling which include the person(s) authorized to take the samples.
22.2.1 There shall be written Standard Operating Procedures for sampling which include the person(s) authorized to take the samples
22.2.2 The sampling instruction shall include:
(a) The method of sampling and the sampling plan, (b) The equipment to be used, (c) any precautions to be observed to avoid contamination of the
material or any deterioration in its quality, (d) The quantity of samples to be taken, (e) instructions for any required sub-division or poling of the samples, (f) The types of sample containers to be used, (g) any specific precautions to be observed, especially in regard to
sampling of sterile and hazardous materials.
22.3. Batch Numbering. -
22.3.1 There shall be Standard Operating Procedures describing the details of the batch (lot) numbering set up with the objective of ensuring that each batch of intermediate, bulk or finished product is identified with a specific batch number.
22.3.2 Batch numbering Standard Operating Procedures applied to a processing stage and to the respective packaging stage shall be same or traceable to demonstrate that they belong to one homogenous mix.
22.3.3 Batch number allocation shall be immediately recorded in a logbook or by electronic data processing system. The record shall include date of allocation, product identity and size of batch.
22.4. Testing:
22.4.1 There shall be written procedures for testing materials and products at different stages of manufacture, describing the methods and equipment to be used. The tests performed shall be recorded.
22.5 Records of Analysis. -
22.5.1 The records shall include the following data:
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(a) name of the material or product and the dosage form (b) batch number and, where appropriate the manufacturer and/ or supplier, (c) reference to the relevant specifications and testing procedures, (d) test results, including observations and calculations, and reference to any
specifications (limits), (e) dates of testing, (f) initials of the persons who performed the testing, (g) initials of the persons who verified the testing and the detailed
calculations, (h) A statement of release or rejection, and (i) signature and date of the designated responsible person.
22.5.2 There shall be written standard operating procedures and the associated records of actions taken for:
(a) equipment assembly and validation (b) analytical apparatus and calibration, (c) maintenance, cleaning and sanitation; (d) personnel matters including qualification, training, clothing, hygiene (e) environmental monitoring; (f) pest control; (g) complaints; (h) recalls made; and (i) returns received.
23. Reference Samples. -
23.1 Each lot of every active ingredient, in a quality sufficient to carryout all the tests, except sterility and pyrogens / Bacterial Endotoxin Test, shall be retained for a period of 3 months after the date of expiry of the last batch produced from that active ingredient.
23.2. Samples of finished formulations shall be stored in the same or simulated containers in which the drug has been actually marketed.
24. Reprocessing and Recoveries. -
24.1. Where reprocessing is necessary, written procedures shall be established and approved by the Quality Assurance Department that shall specify the conditions and limitations of repeating chemical reactions. Such reprocessing shall be validated.
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24.2. If the product batch has to be reprocessed, the procedure shall be authorized and recorded. An investigation shall be carried out into the causes necessitating re-processing and appropriate corrective measures shall be taken for prevention of recurrence. Re-processed batch shall be subjected to stability evaluation.
24.3. Recovery of the product residue may be carried out, if permitted, in the master production and control records by incorporating it in subsequent batches of the product.
25. Distribution records:
25.1. Prior to distribution or dispatch of given batch of a drug, it shall be ensure that the batch has been duly tested, approved and released by the quality control personnel. Pre-dispatch inspection shall be performed on each consignment on a random basis to ensure that only the correct goods are dispatched. Detailed instructions for warehousing and stocking of Large Volume Parenterals, if stocked, shall be in existence and shall be complied with after the batch is released for distribution. Periodic audits of warehousing practices followed at distribution centers shall be carried out and records thereof shall be maintained. Standard Operating Procedures shall be developed for warehousing of products.
25.2. Records for distribution shall be maintained in a manner such that finished batch of a drug can be traced to the retain level to facilitate prompt and complete recall of the batch, if and when necessary.
26. Validation and process validation. -
26.1. Validation studies shall be an essential part of Good Manufacturing Practices and shall b conducted as per the pre-defined protocols. These shall include validation of processing, testing and cleaning procedures.
26.2. A written report summarizing recorded results and conclusions shall be prepared, documented and maintained.
26.3. Processes and procedures shall be established on the basis of validation study and undergo periodic revalidation to ensure that they remain capable of achieving the intended results. Critical processes shall be validated, prospectively for retrospectively.
26.4. When any new Master Formula or method of preparation is adopted, steps shall be taken to demonstrate its suitability for routine processing. The
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defined process, using the materials and equipment specified shall be demonstrated to yield a product consistently of the required quality.
26.5. Significant changes to the manufacturing process, including any changes in equipment or materials that may affect product quality and/or the reproducibility of the process, shall be validated.
27. Product Recalls. -
27.1 A prompt and effective product recall system of defective products shall be devised for timely information of all concerned stockists, wholesalers, suppliers, upto the retail level within the shortest period. The licensee may make use of both print and electronic media in this regard.
27.2. There shall be an established written procedure in the form of Standard Operating Procedure for effective recall of products distributed by the licensee. Recall operations shall be capable of being initiated promptly so as to effectively reach at the level of each distribution channel.
27.3 The distribution records shall be readily made available to the persons designated for recalls.
27.4 The designated person shall record a final report issued, including reconciliation between the delivered and the recovered quantities of the products.
27.5 The effectiveness of the arrangements for recalls shall be evaluated from time to time.
27.6 The recalled products shall be stored separately in a secured segregated area pending final decision on them.
28. Complaints and Adverse Reactions.
28.1 All complaints thereof concerning product quality shall be carefully reviewed and recorded according to written procedures. Each complaint shall be investigated /evaluated by the designated personnel of the company and records of investigation and remedial action taken thereof shall be maintained.
28.2. Reports of serious adverse drug reactions resulting from the use of a drug along with comments and documents shall be forthwith reported to the concerned licensing authority.
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28.3 There shall be written procedure describing the action to be taken, recall to be made of the defective product.
29. Site Master File. –The licensee shall prepare a succinct document in the form of Site Master File containing specific and factual Good Manufacturing Practices about the production and/or control of pharmaceutical manufacturing preparations carried out at the licensed premises. It shall contain the following: -
29.1 General information, - (a) brief information of the firm; (b) pharmaceutical manufacturing activities as permitted by the licensing authority; (c) other manufacturing activities, if any, carried out on the premises; (d) type of product licensed for manufacture with flow charts mentioning
procedure and process flow; (e) number of employees engaged in the production, quality control, storage and
distribution; (f) use of outside scientific, analytical or other technical assistance in relation to
manufacture and analysis; (g) short description of the Quality Management System of the firm; and (h) products details registered with foreign countries.
29.2 Personnel. -
(a) organisational chart showing the arrangement for quality assurance including production and quality control;
(b) qualification, experience and responsibilities of key personnel; (c) outline for arrangements for basic and in-service training and how the records
are maintained; (d) health requirements for personnel engaged in production; and (e) personal hygiene requirements, including clothing.
29.3 Premises. - (a) simple plan or description of manufacturing areas drawn to scale; (b) nature of construction and fixtures/fittings; (c) brief description of ventilation systems. More details should be given for
critical areas with potential risk of airborne contami nation (schematic drawing of systems). Classification of the rooms used for the manufacture of sterile products should be mentioned;
(d) special areas for the handling of the highly toxic, hazardous and sensitizing materials;
(e) brief description of water system (schematic drawings of systems), including
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sanitation; and (f) description of planned preventive maintenance programs for premises and of
the recording system.
29.4 Equipment. -
(a) brief description of major equipment used in production and Quality Control Laboratories (a list of equipment required);
(b) description of planned preventive maintenance programs for equipment and of the recording system; and
(c) qualification and calibration including the recording systems and arrangements for computerized systems validation.
29.5 Sanitation. -
(a) availability of written specifications and procedures for cleaning manufacturing areas and equipment.
29.6 Documentation. -
(a) arrangements for the preparation, revision and distribution of; (b) necessary documentation for the manufacture; (c) any other documentation related to product quality that is not mentioned
elsewhere (e.g. microbiological controls about air and water). 29.7 Production. -
(a) brief description of production operations using, wherever possible, flow sheets and charts specifying important parameters;
(b) arrangements for the handling of starting materials, packaging materials, bulk and finished products, including sampling, quarantine, release and storage;
(c) arrangements for the handling of rejected materials and products; and (d) brief description of general policy for process validation.
29.8 Quality Control. -
(a) description of the quality control system and of the activities of the Quality Control Department. Procedures for the release of the finished products.
29.9 Loan licence manufacture and licensee. -
(a) description of the way in which compliance of Good Manufacturing Practices by the loan licensee shall be assessed.
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29.10 Distribution, complaints and product recall. -
(a) arrangements and recording system for distribution; and
(b) arrangements for handling of complaints and product recalls.
29.11 Self inspection. -
(a) short description of the self inspection system indicating whether an outside, independent and experienced external export was involved in evaluating the manufacturer’s compliance with Good manufacturing Practices in all aspects of production.
29.12 Export of drugs. -
(a) products exported to different countries; and (b) complaints and product recall, if any.
PART I-A
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF STERILE PRODUCTS, PARENTERAL PREPARATIONS (SMALL VOLUME INJECTABLES AND LARGE VOLUME
PARENTERALS) AND STERILE OPHTHALMIC PREPARATIONS.
Note. - The general requirements as given in Part 1 of this Schedule relating to Requirements of Good Manufacturing Practices for Premises and Materials for pharmaceutical products shall be complied with, mutatis mutandis, for the manufacture of sterile products, Parenteral preparations (Small Volume Injectables and Large Volume Parenterals) and Sterile Ophthalmic Preparations. In addition to these requirements, the following specific requirements shall also be followed, namely: -
1. General Sterile products, being very critical and sensitive in nature, a very high degree of
precautions, prevention and preparations and needed. Dampness, dirt and darkness are to be avoided to ensure aseptic conditions in all areas. There shall be strict compliance in the prescribed standards especially in the matter of supply of water, air, active materials and in the maintenance of hygienic environment.
2. Building and Civil Works. -
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2.1 The building shall be built on proper foundation with standardized materials to avoid cracks in critical areas like aseptic solution preparation, filling and sealing rooms.
2.2 Location of services like water, steam, gases etc. shall be such that their servicing or repair shall not pose any threat to the integrity of the facility. Water lines shall not pose any threat of leakage to aseptic area.
2.3. The manufacturing areas shall be clearly separated into support areas (e.g. washing and component preparation areas, storage areas etc.), preparation areas (e.g. bulk manufacturing area, non-aseptic blending areas etc.) change areas and aseptic areas. Operations like removal of outer cardboard wrappings of primary packaging materials shall be done in the de-cartoning areas which are segregated from the washing areas. Wooden pallets, fiberboard drugs, cardboard and other particle shedding materials shall not be taken inside the preparation areas.
2.4 In aseptic areas –
(a) walls, floors and ceiling should be impervious, non-shedding, non-flaking and non-cracking. Flooring should be unbroken and provided with a cove both at the junction between the wall and the floor as well as the wall and ceiling.
(b) walls shall be flat, and ledges and recesses shall be avoided. Wherever other surfaces join the wall (e,g, sterilizers, electric sockets, gas points etc.) these shall flush the walls. Walls shall be provided with a cove at the joint between the ceiling and floor;
(c) ceiling shall be solid and joints shall be sealed. Light-fittings and air-grills shall flush with the walls and not hanging from the ceiling, so as to prevent contamination.
(d) there shall be no sinks and drains in Grade A and Grade B areas.
(e) doors shall be made of non-shedding ma terial. These may be made preferably of Aluminium or Steel material. Wooden doors shall not be used. Doors shall open towards the higher-pressure area so that they close automatically due to air pressure.
(f) Windows shall be made of similar material as the doors, preferably with double panel and shall be flush with the walls. If fire escapes are to be provided, these shall be suitably fastened to the walls without any gaps;
(g) The furniture used shall be smooth, washable and made of stainless steel or any other appropriate material other than wood.
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2.5. The manufacturing and support areas shall have the same quality of civil structure described above for aseptic areas, except the environmental standards which may vary in the critical areas.
2.6 Change rooms with entrance in the form of air-locks shall be provided before entry into the sterile product manufacturing areas and then to the aseptic area. Separate exit space from the aseptic areas is advisable. Change rooms to the aseptic areas shall be clearly demarcated into ‘black’. ‘gray’, and ‘white rooms’ with different levels of activity and air cleanliness. The ‘black’ change room shall be provided with a hand-washing sink. The sink and its drain in the un-classified (first) change rooms may be kept clean all the time. The specially designed drain shall be periodically monitored to avoid presence of pathogenic microorganisms. Change room doors shall not be opened simultaneously. An appropriate inter-locking system and a visual and/or audible warning system may be installed to prevent the opening of more than one door at a time.
2.7. For communication between aseptic areas and non-aseptic areas, intercom telephones or speak-phones shall be used. These shall be minimum in number.
2.8 Material transfer between aseptic areas and outside shall be through suitable airlocks or pass-boxes. Doors of such airlocks and pass-boxes shall have suitable interlocking arrangements.
2.9. Personal welfare areas like rest rooms, tea room, canteen and toilets shall be outside and separated from the sterile product manufacturing area.
2.10 Animal houses shall be away from the sterile product manufacturing area and shall not share a common entrance or air handling system with the manufacturing area.
3.Air Handling System (Central Air-Conditioning). -
3.1 Air Handling Units for sterile product manufacturing areas shall be different from those for other areas. Critical areas, such as the aseptic filling area, sterilized components unloading area and change room conforming to Grades B, C and D respectively shall have separate air handling units. The filter configuration in the air handling system shall be suitably designed to achieve the Grade of air as given in Table1. Typical operational activities for clean areas are highlighted in Table II and Table III.
3.2 For products which are filled aseptically, the filling room shall meet Grade B conditions at rest unmanned. This condition shall also be obtained within a period of about 30 minutes of the personnel leaving the room after completion of operations.
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3.3. The filling operations shall take place under Grade A conditions which shall be demonstrated under working of simulated conditions which shall be achieved by providing laminar air flow work stations with suitable HEPA filters or isolator technology.
3.4. For products, which are terminally sterilized, the filling room shall meet Grade C conditions at rest. This condition shall be obtainable within a period of about 30 minutes of the personnel leaving the rook after completion of operations.
3.5. Manufacturing and component preparation areas shall meet Grade C conditions.
3.6. After completion of preparation, washed components and vessels shall be protected with Grade C background and if necessary, under laminar air flow work station.
3.7. The minimum air changes for Grade B and Grade C areas shall not be less than 20 air changes per hour in a room with god air flow pattern and appropriate HEPA filters. For Grade A laminar air flow work stations, the air flow rate shall be 0.3 meter per second ± 20% (for vertical flows) and 0.45 meter per second ± 20% (for horizontal flows).
3.8. Differential pressure between areas of different environmental standards shall be at least 15 Pascal (0.06 inches or 1.5mm water gauge). Suitable manometers or gauges shall be installed to measure and verify pressure differential.
3.9 The final change room shall have the same class or air as specified for the aseptic area. The pressure differentials in the change roods shall be in the descending order from ‘white’ to ‘black’.
3.10 Unless there are product specific requirements, temperature and humidity in the aseptic areas shall not exceed 27 degree centigrade and relative humidity 55%, respectively.
TABLE I AIRBORNE PARTICULATE CLASSIFICATION FOR MANUFACTURE
OF STERILE PRODUCTS. Grade At rest (b) In Operation (a)
Maximum number of permitted particles per cubic metre equal to or above.
0.5µm 5µm 0.5µm 5µm A 3520 29 3500 29 B (a) 35,200 293 3,52,000 2,930 C (a) 3,52,000 2,930 35,20,000 29,300 D (a) 35,20,000 29,300 Not defined (c) Not defined (c)
Notes :
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(a) In order to reach the B, C and D air grades, the number of air changes shall be related to the size of the room and the equipment and personnel present in the room. The air system shall be provided with the appropriate filters such as HEPA for Grade A, B and C. the maximum permitted number of particles in the “at rest” condition shall approximately be as under: Grade A corresponds with Class 100 or M 3.5 or ISO Class 5; Grade B with Class 1000 or M 4.5 ISO Class 6; Grade C with Class 10,000 or M 5.5 or ISO Class 7; Grade D with Class 100,000 or M 6.5 or ISO Class 8.
(b) The requirement and limit for the area shall depend on the nature of the operation carried out.
(c) Type of operations to be carried out in the various grades are given in Table II and Table III as under.
TABLE II
TYPES OF OPERATIONS TO BE CARRIED OUT IN THE VARIOUS GRADES FOR ASEPTIC PREPARATIONS
Grade Types of operations for aseptic preparations A Aseptic preparation and filling B Background room conditions for activities requiring Grade A C Preparation of solution to be filtered D Handling of components after washing
TABLE III
TYPES OF OPERATIONS TO BE CARRIED OUT IN THE VARIOUS GRADES FOR TERMINALLY STERILIZED PRODUCTS.
Grade Types of operations for terminally sterilized products. A Filling of products, which are usually at risk C Placement of filling and sealing machines, preparation of solutions when usually
at risk. Filling of product when unusually at risk. D Moulding, blowing (pre-forming) operations of plastic containers, preparations of
solutions and components for subsequent filling
4. Environmental Monitoring
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4.1 All environmental parameters listed under para 3.1 to 3.10 shall be verified and established at the time of installation and thereafter monitored at periodic intervals. The recommended frequencies of periodic monitoring shall be as follows :-
(a) Particulate monitoring in air – 6 Monthly. (b) HEPA filter integrity testing (smoke testing) – Yearly (c) Air change rates – 6 Monthly. (d) Air pressure differentials – Daily. (e) Temperature and humidity – Daily (f) Microbiological monitoring by settle plates and/or swabs in aseptic areas -
daily, and at decreased frequency in other areas
Note: The above frequencies of monitoring shall be changed as per the requirements and load in individual cases.
4.2 There shall be a written environmental monitoring program and microbiological results shall be recorded. Recommended limits for microbiological monitoring of clean areas “in operation” are as given in the table below:
TABLE
RECOMMENDED LIMITS FOR MICROBIOLOGICAL MONITORING OF CLEAN AREAS “ IN OPERATION”
Grade Air sample Cfu/m2
Settle plates (dia. 90mm. Cfu/2 hrs.
Contact plates (dia. 55mm) cfu per plate
Glove points (five fingers) cfu per glove
A < 1 < 1 < 1 < 1 B 10 5 5 5 C 100 50 25 -- D 500 100 50 --
Notes:
(a) These are average values. (b) Individual settle plates may be exposed for not less than two hours in Grade B,
C and D areas and for not less than thirty minutes in Grade A area.
4.3 Appropriate action shall be taken immediately if the result of particulate and microbiological monitoring indicates that the counts exceed the limits. The Standard Operating Procedures shall contain corrective action. After major engineering modification to the HVAC system of any area, all monitoring shall be re-performed before production commences.
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5.Garments.
5.1 This section covers garments required for use by personnel working only in aseptic area.
Outdoor clothing shall not be brought into the sterile areas.
5.2 The garments shall be made of non-shedding and tight weave material. Cotton garments shall not be used. The garments shall shed virtually no fibres or particulate matter.
5.3 The clothing and its quality shall be adopted to the process and the work place and worn in such a way as to protect the product from contamination. Garments shall be single piece with fastenings at cuffs, neck and at legs to ensure close fit. Trouser legs shall be tucked inside the cover boots. Suitable design of garments shall either include a hood (head-cover) or a separate hood which can be tucked inside the over-all. Pockets, pleats and belts shall be avoided in garments. Zips (if any) shall be of plastic material. Garments with damaged zips shall not be used.
5.4. Only clean, sterilized and protective garments shall be used at each work session where aseptic filtration and filling operations are undertaken and at each work shift for products intended to be sterilized, post-filling. The mask and gloves shall be changed at every work session in both instances.
5.5 Gloves shall be made of latex or other suitable plastic materials and shall be powder- free. These shall be long enough to cover wrists completely and allow the over-all cuff to be tucked in.
5.6. The footwear shall be of suitable plastic or rubber material and shall be daily cleaned with a bactericide.
5.7. Safety goggles or numbered glasses with side extension shall be used inside aseptic areas. These shall be sanitized by a suitable method.
5.8. Garment changing procedures shall be documented and operators trained in this respect. A full size mirror shall be provided in the final change room for the operator to verify that he is appropriately attired in the garments. Periodic inspection of the garments shall be done by responsible staff.
6. Sanitation- 6.1. There shall be written procedures for the sanitation of sterile processing facilities.
Employees carrying out sanitation of aseptic areas shall be trained specifically for this purpose.
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6.2. Different sanitizing agent shall be used in rotation and the concentrations of the same shall be as per the recommendations of the manufacturer. Records of rotational use of sanitizing agents shall be maintained.
6.3. Distilled water freshly collected directly from the distilled water plant or water maintained above 70 degree centigrade from the re-circulation loop shall be used for dilution of disinfectants. Alternatively, distilled water sterilized by autoclaving or membrane filtration shall be used. The dilution shall be carried out in the ‘white’ change room.
6.4. Where alcohol or isopropyl alcohol is used for dilution of disinfectants for use as hand sprays, the preparation of the same shall be done in the bulk preparation area and diluted solution membrane filtered into suitable sterile containers held in aseptic area.
6.5. Diluted disinfectants shall bear the label ‘use before’, based on microbiological establishment of the germicidal properties. The solutions shall be adequately labeled and documents maintained.
6.6. Formaldehyde or any other equally effective fumigant is recommended for the fumigation of aseptic areas or after major civil modifications. There shall be Standard Operating Procedures for this purpose. Its use for routine purpose shall be discouraged and an equally effective surface cleaning regime shall be followed.
6.7. Cleaning of sterile processing facilities shall be undertaken with air suction devices or with non-linting sponges or clothes.
6.8. Air particulate quality shall be evaluated on a regular basis and record maintained.
7.Equipment.
7.1 The special equipment required for manufacturing sterile products includes component washing machines, steam sterilizers, dry heat sterilizers, membrane filter assemblies, manufacturing vessels, blenders, liquid filling machines, powder filling machines, sealing and labeling machines, vacuum testing chambers, inspection machines, lyophilisers, pressure vessels etc. suitable and fully integrated washing sterilizing filling lines may be provided, depending upon the type and volume of activity.
7.2. Unit-sterilizers shall be double-ended with suitable inter-locking arrangements between the doors. The effectiveness of the sterilization process shall be established initially by biological inactivation studies using microbial spore indicators and then at least once a year by carrying out thermal mapping of the chamber. Various sterilization parameters shall be established based on these studies and documented. For membrane filters used for filtration, appropriate filter integrity tests that ensure sterilization shall be carried out before and after filtration.
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7.3. Filling machines shall be challenged initially and then at periodic intervals by simulation trials including sterile media fill. Standard Operating Procedures and acceptance criteria for media fills shall be established, justified and documented. Special simulation trial procedures shall be developed, validated and documented for special products like ophthalmic ointments.
7.4. The construction material used for the parts which are in direct contact with products and the manufacturing vessels may be stainless steel 316 or Boro-silicate glass (if glass containers) and the tubing shall be capable of being washed and autoclaved.
7.5 On procurement, installation qualification of each of the equipment shall be done by engineers with the support of production and quality assurance personnel. Equipment for critical processes like aseptic filling and sterilizers shall be suitably validated according to a written program before putting them to use.
7.6. Standard Operating Procedures shall be available for each equipment for its calibration and operation and cleaning. Gauges and other measuring devices attached to equipment shall be calibrated at suitable intervals against a written program. Calibration status of equipment gauges shall be adequately documented and displayed.
8.Water and Steam Systems –
8.1. Potable water meeting microbiological specification of not more than 500 cfu/ml and indicating absence of individual pathogenic microorganisms, Escherichia coli, Salmonella, Staphylococcus aureus and Pseudomonas aeruginosa per 100 ml sample shall be used for the preparation of purified water.
8.2 Purified water prepared by de-mineralization shall meet the microbiological specification of not more than 100 cfu per ml and indicate absence of pathogenic micro- organisms in 100 ml. Purified water shall also meet IP specification for chemical quality. Purified water shall be used for hand washing in change rooms. Containers, closures and machine parts may be washed with potable water followed by suitably filtered purified water. Purified water shall be stored in stainless steel tanks or plastic tanks.
8.3. Water for Injection (hereinafter as WFI) shall be prepared from potable water or purified water meeting the above specifications by distillation. Water for Injection shall meet microbiological specification of not more than 10 cfu per 100 ml. WFI shall also met IP specification for Water for Injection and shall have an endotoxin level of not more than 0.25 EU/Ml. bulk solutions of liquid parenterals shall be made in WFI. Final rinse of product containers and machine parts shall be done with WFI. Disinfectant solutions for use in aseptic areas shall be prepared in WFI.
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8.4. Water for Injection for the manufacture of liquid injectables shall be freshly collected from the distillation plant or from a storage or circulation loop where the water has been kept at above 70 degree centigrade. At the point of collection, water may be cooled using suitable heat exchanger.
8.5 Water for non-injectable sterile products like eye drops shall meet IP specifications for purified water. In addition, microbiologial specification of not more than 10 cfu per 100ml and absence of Pseudomonas aeruginosa and Enterobacter coli in 100 m shall also be met.
8.6. Water for Injection shall be stored in steam jacketed stainless steel tanks of suitable size and the tanks shall have hydrophobic bacterial retention with 0.2 µ vent filters. The filters shall be suitably sterilized at periodic intervals. The distribution lines for purified water and distilled water shall be of stainless steel 316 construction and shall not shed particles.
8.7. There shall be a written procedure and program for the sanitation of different water systems including storage tanks, distribution lines, pumps and other related equipment. Records of sanitation shall be maintained.
8.8. There shall be written microbiological monitoring program for different types of water. The results shall justify the frequency of sampling and testing. Investigation shall be carried out and corrective action taken in case of deviation from prescribed limits.
8.9 Steam coming in contact with the product, primary containers and other product contact surfaces shall be sterile and pyrogen free. The steam condensate shall meet microbiological specification of not more than 10 cfu per 100ml. the condensate shall also meet IP specification for Water for Injection and shall have an endotoxin levels of not more than 0.25 EU/ml. there shall be a suitable schedule for the monitoring of steam quality.
9.Manufacturing Process –
9.1. Manufacture of sterile products shall be carried out only in areas under defined conditions.
9.2. Bulk raw materials shall be monitored for bio-burden periodically. Bio-burden of bulk solution prior to membrane filtration shall be monitored periodically and a limit of not more than 100 cfu per ml is recommended.
9.3 The time between the start of the preparation of the solution and its sterilization or filtration through a micro-organism retaining filter shall be minimized. There shall be a set maximum permissible time for each product that takes into account its composition and method of storage mentioned in the Master formula record.
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9.4. Gases coming in contact with the sterile product shall be filtered through two 0.22 µ hydrophobic filters connected in-series. These filters shall be tested for integrity. Gas cylinders shall not be taken inside aseptic areas.
9.5.Washed containers shall be sterilized immediately before use. Sterilized containers, if not used within an established time, shall be rinsed with distilled or filtered purified water and re-sterilized.
9.6. Each lot of finished product shall be filled in one continuous operation. In each case, where one batch is filled in using more than one operation, each lot shall be tested separately for sterility and held separately till sterility test results are known.
9.7. Special care shall be exercised while filling products in powder form so as not to contaminate the environment during transfer of powder to filling machine-hopper.
10 Form-Fill-Seal Technology or Blow, Fill-Seal Technology. -
10.1 Form-Fill-Seal units are specially built automated machines in which through one continuous operation, containers are formed from thermoplastic granules, filled and then sealed. Blow, fill-seal units are machines in which containers are moulded / blown (pre- formed) in separate clean rooms, by non-continuous operations.
Note: -
(i) These shall be installed in at least Grade C environment. (ii) These shall comply with the limits as recommended in Table at Item 4.2.
10.2. Form-Fill-Seal/Blow, Fill-Seal machines used for the manufacture of products for terminal sterilization shall be installed in at least Grade C environment and the filling zone within the machine shall fulfill Grade A requirements.
10.3. Terminally sterilized products. -
10.3.1. Preparation of primary packaging material such as glass bottles, ampoules and rubber stoppers shall be done in at least Grade D environment. Where there is unusual risk to the product from microbial contamination, the above operation shall be done in Grade C environment. All the process used for component preparation shall be validated.
10.3.2. Filling of products requiring terminal sterilization shall be done under Grade A environment with a Grade C background.
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10.4 Preparation of solutions, which are to be sterilized by filtration, shall be done in Grade C environment, and if not to be filtered, the preparation of materials and products shall be in a Grade A environment with Grade B in background.
10.5 Filtration (membrane).-
(i) Solutions for Large Volume Parenterals shall be filtered through a non-fibre releasing, sterilizing grade cartridge/membrane filter of nominal pore size of 0.22 µ for aseptic filling whereas 0.45 µ porosity shall be used for terminally sterilized products.
(ii) A second filtration using another 0.22 µ sterilizing grade cartridge / membrane filter shall be performed immediately prior to filling. Process specifications shall indicate the maximum time during which a filtration system may be used with a view to precluding microbial build-up to levels that may affect the microbiological quality of the Large Volume Parenterals.
(iii) The integrity of the sterilized filter shall be verified and confirmed immediately after use by an appropriate method such as Bubble Point, Diffusive Flow or Pressure Hold Test.
10.6 Sterilization (Autoclaving).-
10.6.1. Before any sterilization process is adopted, its suitability for the product and its efficacy in achieving the desired sterilizing conditions in all parts of each type of load pattern to be processed, shall be demonstrated by physical measurements and by biological indicators, where appropriate.
10.6.2 All the sterilization process shall be appropriately validated. The validity of the process shall be verified at regular intervals, but at least annually. Whenever significant modifications have been made to the equipment and product, records shall be maintained thereof.
10.6.3 The sterilizer shall be double ended to prevent mix-ups.
10.6.4 Periodic bio-burden monitoring of products before terminal sterilization shall be carried out and controlled to limits specified for the product in the Master Formula.
10.6.5 The use of biological indicators shall be considered as an additional method of monitoring the sterilization. These shall be stored and used according to the manufacturer’s instructions. Their quality shall be checked by positive controls. If biological indicators used, strict precautions shall be taken t avoid transferring microbial contamination from them.
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10.6.6 There shall be clear means of differentiating ‘ sterilized’ and ‘un-sterilized’ products. Each basket, tray or other carrier of products or components shall be clearly labeled with the name of the material, its batch number, and sterilization status. Indicators shall be used, where appropriate, to indicate whether a batch (or sub-batch) has passed through the sterilization process.
10.6.7 Sterilization records shall be available for each sterilization run and may also include thermographs and sterilization monitoring strips. They shall be maintained as part of the batch release procedure.
10.7. Sterilization (by dry heat).-
10.7.1 Each heat sterilization cycle shall be recorded on a time/temperature chart of a suitable size by appropriate equipment of the required accuracy and precision. The position of temperature probes used for controlling and/or recording shall be determined during the validation and, where applicable, shall also be checked against a second independent temperature probe located in the same position. The chart shall form a part of the batch record. Container mapping may also be carried out in the case of Large Volume Parenterals.
10.7.2 Chemical or biological indicators may also be used, but shall take the place of physical validation.
10.7.3. Sufficient time shall be allowed for the load to reach the required temperature before measurement of sterilization time commences. This time shall be separately determined for each type of load to be processed.
10.7.4. After the high temperature phase of a heat sterilization cycle, precautions shall be taken against contamination of sterilized load during cooling. Any cooling fluid or gas in contact with the product shall be sterilized unless it can be shown that any leaking container would not be approved for use. Air inlet and outlets shall be provided with bacterial retaining filters.
10.7.5. The process used for sterilization by dry heat shall include air-circulation within the chamber and the maintenance of a positive pressure to prevent the entry of non-sterile air. Air inlets and outlets should be provided with micro-organism retaining filters. Where this process of sterilization by dry heat is also intended to remove pyrogens, challenge tests using endotoxins would be required as part of the validation process.
10.8. Sterilization (by moist heat).-
10.8.1 Both the temperature and pressure shall be used to monitor the process. Control instrumentation shall normally be independent of monitoring instrumentation and recording charts. Where automated control and monitoring systems are used for these applications, these
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shall be validated to ensure that critical process requirements are met. System and cycle faults shall be registered by the system and observed by the operator. The reading of the independent temperature indicator shall be routinely checked against the chart-recorder during the sterilization period. For sterilizers fitted with a drain at the bottom of the chamber, it may also be necessary to record the temperature at this position throughout the sterilization period. There shall be frequent leak tests done on the chamber during the vacuum phase of the cycle.
10.8.2 The items to be sterilized, other than products in sealed containers, shall be wrapped in a material which allows removal of air and penetration of steam but which prevents re-contamination after sterilization. All parts of the load shall be in contact with the sterilizing agent at the required temperature of the required time.
10.8.3. No Large Volume Parenteral shall be subjected to steam sterilization cycle until it has been filled and sealed.
10.8.4 Care shall be taken to ensure that the steam used for sterilization is of a suitable quality and does not contain additives at a level which could cause contamination of the product or equipment.
10.9. Completion/finalisation of sterile products.-
10.9.1. All unit operations and processes in the manufacture of a batch shall have a minimum time specified and the shortest validated time shall be used from the start of a batch to its ultimate release for distribution.
10.9.2. Containers shall be closed by appropriately validated methods. Containers closed by fusion e.g. glass or plastic ampoules shall be subjected to 100% integrity testing. Samples of other containers shall be checked for integrity according to appropriate procedures.
10.9.3 Containers sealed under vacuum shall be tested for required vacuum conditions.
10.9.4 Filled containers parenteral products shall be inspected individually for extraneous contamination or other defects. When inspection is done visually, it shall be done under suitably controlled conditions of illumination and background. Operators doing the inspection shall pass regular eye-sight checks with spectacles, if worn, and be allowed frequent rest from inspection. Where other methods of inspection are used, the process shall be validated and the performance of the equipment checked at suitable intervals. Results shall be recorded.
11. Product Containers and Closures.
11.1 All containers and closures intended for use shall comply with the pharmacopoeial and other specified requirements. Suitable samples sizes, specifications, test methods, cleaning procedures and sterilization procedures, shall be used to assure that containers,
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closures and other component parts of drug packages are suitable and are not reactive, additive, adsorptive or leachable or presents the risk of toxicity to an extent that significantly affects the quality or purity of the drug. No second hand or used containers and closures shall be used.
11.2 Plastic granules shall also comply with the pharmacopoeial requirements including physio-chemical and biological tests.
11.3. All containers and closures shall be rinsed prior to sterilization with Water for Injection according to written procedure.
11.4. The design of closures, containers and stoppers shall be such as to make cleaning, easy and also to make airtight seal when fitted to the bottles.
11.5 It shall be ensured that containers and closures chosen for a particular product are such that when coming into contact they are not absorbed into the product and they do not affect the product adversely. The closures and stoppers should be of such quality substances as not to affect the quality of the product and avoid the risk of toxicity.
11.6. Whenever glass bottles are used, the written schedule of cleaning shall be laid down and followed. Where bottles are not dried after washing, these shall be finally rinsed with distilled water or pyrogen free water, as the case may be, according to written procedure.
11.7. Individual containers of parenteral preparations, ophthalmic preparations shall be examined against black/white background fitted with diffused light after filling so as to ensure freedom from foreign matters.
11.8 Glass Bottles.-
11.8.1 Shape and design of the glass bottle shall be rational and standardized. Glass bottles made of USP Type-I and USP Type-II glass shall only be used. Glass bottles shall not be reused. Before use, USP Type-II bottles shall be validated for the absence of particulate matter generated over a period of the shelf life of the product and shall be regularly monitored after the production, following statistical sampling methods. USP Type-III glass containers may be used for non-parenteral sterile products such as Otic Solutions.
11.9. Plastic Containers.-
11.9.1 Pre-formed plastic containers intended to be used for packing of Large Volume Parenteral shall be moulded in-house by one-continuous operation through an automatic machine.
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11.9.2. Blowing, filling and sealing (plugging) operation shall be conducted in room(s) conforming to requirements as mentioned in Table III of Item 3.10. Entry to the area where such operations are undertaken, shall be through a series of airlocks. Blowers shall have an air supply which is filtered through 0.22µ filters. Removal of runners and plugging operations shall be conducted under a laminar airflow workstation.
11.10 Rubber Stoppers.-
11.10.1 The tuber stoppers used for Large Volume Parenterals shall comply with specifications prescribed in the current edition of the Indian Pharmacopoeia.
12. Documentation
12.1 The manufacturing records relating to manufacture of sterile products shall indicate the following details:-
(1) Serial number of the Batch Manufacturing Record. (2) Name of the product (3) Reference to Master Formula Record. (4) Batch/Lot number (5) Batch/Lot size. (6) Date of commencement of manufacture and date of completion of
manufacture. (7) Date of manufacture and assigned date of expiry. (8) Date of each step in manufacturing. (9) Names of all ingredients with the grade given by the quality control
department. (10) Quality of all ingredients. (11) Control reference numbers for all ingredients. (12) Time and duration of blending, mixing, etc. whenever applicable. (13) pH of solution whenever applicable. (14) Filter integrity testing records (15) Temperature and humidity records whenever applicable (16) Records of plate-counts whenever applicable. (17) Results of pyrogen and/or bacterial endotoxin & toxicity. (18) Results of weight or volume of drug filled in containers. (19) Bulk sterility in case of aseptically filled products. (20) Leak test records. (21) Inspection records. (22) Sterilization records including autoclave leakage test records, load details,
date, duration, temperature, pressure, etc. (23) Container washing records. (24) Total number of containers filled.
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(25) Total numbers of containers rejected at each stage (26) Theoretical yield, permissible yield, actual yield and variation thereof. (27) Clarification for variation in yield beyond permissible yield. (28) Reference numbers of relevant analytical reports. (29) Details of reprocessing, if any. (30) Name of all operators carrying out different activities. (31) Environmental monitoring records. (32) Specimens of printed packaging materials. (33) Records of destruction of rejected containers printed packaging and testing. (34) Signature of competent technical staff responsible for manufacture and testing.
Note: (1) Products shall be released only after complete filling and testing. (2) Result of the tests relating to sterility, pyrogens, and Bacterial
endotoxins shall be maintained in the analytical records. (3) Validation details and simulation trail records shall be maintained
separately, (4) Records of environmental monitoring like temperature, humidity,
microbilogical data, etc. shall be maintained. Records of periodic servicing of HEPA filters, sterilizers and other periodic maintenance of facilities and equipment carried out also be maintained.
(5) Separate facilities shall be provided for filling-cum-sealing of Small Volume Parenterals in glass containers and/or plastic containers,
(6) It is advisable to provide separate facilities for manufacture of Large Volume Parenterals in glass containers and / or plastic containers.
(7) For manufacture of Large Volume Parenterals in plastic containers, it is advisable to install automatic (with all operations) Form–Fill-Seal machines having one continuous operation.
PART I-B
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL SOLID DOSAGE FORMS (TABLETS AND CAPSULES)
Note: - The General Requirements as given in Part 1 of this Schedule relating to requirements of Good Manufacturing Practices for Premises and materials for pharmaceutical products shall be complied with, mutates mutandis, for the manufacture of oral Solid Dosage Forms (Tablets and Capsules). In addition to these requirements, the following Specific Requirement shall also be followed, namely :-
1. General-
1.1 The processing of dry materials and products creates problems of dust control and cross-contamination. Special attention is therefore, needed in the design, maintenance and use
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of premises and equipment in order to overcome these problems. Wherever required, enclosed dust control manufacturing systems shall be employed.
1.2. Suitable environmental conditions for the products handled shall be maintained by installation of air-conditioning wherever necessary. Effective air-extraction systems, with discharge points situated to avoid contamination of other products and professes shall be provided. Filters shall be installed to retain dust and protect the factory and local environment.
1.3. Special care shall be taken to protect against subsequent contamination of the product by particles of metal or wood. The use of metal detector is recommended. Wooden equipment should be avoided. Screens, sieves, punches and dies shall be examined for wear and tear or for breakage before and after each use.
1.4. All ingredients for a dry product shall be sifted before use unless the quality of the input material can be assured. Such sifting shall normally be carried out at dedicated areas.
1.5. Where the facilities are designed to provide special environmental conditions of pressure differentials between rooms, these conditions shall be regularly monitored and any specification results brought to the immediate attention of the Production and quality Assurance Department which shall be immediately attended to.
1.6. Care shall be taken to guard against any material lodging and remaining undetected in any processing or packaging equipment. Particular care shall be taken to ensure that any vacuum, compressed air or air-extraction nozzles are kept clean and that there is no evidence lubricants leaking into the product from any part of the equipment.
2. Sifting, Mixing and Granulation.
2.1. Unless operated as a closed system, mixing, sifting and blending equipments shall be fitted with dust extractors.
2.2. Residues from sieving operations shall be examined periodically for evidence of the presence of unwanted materials.
2.3. Critical operating parameters like time and temperature for each mixing, blending and drying operation shall be specified in a Master Formula, monitored during processing, and recorded in the batch records.
2.4. Filter bags fitted to fluid-bed drier shall not be used for different products, without being washed in-between use. With certain highly potent or sensitizing products, bags specific to one product only shall be used. Air entering the drier shall be filtered. Steps shall be taken to prevent contamination of the site and local environment by dust in the air leaving the drier due to close positioning of the air-inlets and exhaust.
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2.5.Granulation and coating solutions shall be made, stored and used in a manner which minimizes the risk of contamination or microbial growth.
3. Compressions (Tablets)
3.1. Each tablets compressing machine shall be provided with effective dust control facilities to avoid cross-contamination. Unless the same product is being made on each machine, or unless the compression machine itself provides its own enclosed air controlled environment, the machine shall be installed in separate cubicles.
3.2. Suitable physical,, procedural and labeling arrangements shall be made to prevent mix up of materials, granules and tables on compression machinery.
3.3. Accurate and calibrated weighting equipment shall be readily available and used for in-process monitoring of tablet weight variation. Procedures used shall be capable of detecting out-of-limits tablets.
3.4 At the commencement of each compression run and in case of multiple compression points in a compression machine, sufficient individual tablets shall be examined at fixed intervals to ensure that a tablet from each compression station or from each compression point has been inspected for suitable pharmacopoeial parameters like ‘appearance’, ‘weight variation’, ‘disintegration’, ‘hardness’, ‘friability’ and ‘thickness’. The results shall be recorded as part of the batch documentation.
3.5. Tablets shall be de-dusted, preferably by automatic device and shall be monitored for the presence of foreign materials besides any other defects.
3.6. Tablets shall be collected into clean, labeled containers.
3.7. Rejected or discarded tablets shall be isolated in identified containers and their quality recorded in the Batch Manufacturing Record.
3.8 In-process control shall be employed to ensure that the products remain within specification. During compression, samples of tablets shall be taken at regular intervals of not greater than 30 minutes to ensure that they are being produced in compliance with specified in-process specification. The tablets shall also be periodically checked for additional parameters such as ‘appearance’, ‘weight variation’, ‘disintegration’, ‘hardness’, ‘friability’ and ‘thickness’ and contamination by lubricating oil.
4. Coating (Tablets)
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4.1. Air supplied to coating pans for drying purposes shall be filtered air and of suitable quality. The area shall be provided with suitable exhaust system and environmental control (temperature, humidity) measures.
4.2 Coating solutions and suspensions shall be made afresh and used in a manner, which shall minimize the risk of microbial growth. Their preparation and use shall be documented and recorded.
5. Filling of Hard Gelatin Capsule.
Empty capsules shells shall be regarded as ‘drug component’ and treated accordingly. They shall be stored under conditions which shall ensure their safety from the effects of excessive heat and moisture.
6. Printing (Tablets and Capsules)
6.1. Special care shall be taken to avoid product mix-up during any printing of tablets and capsules. Where different products, or different batches of the same product, are printed simultaneously, the operations shall adequately be segregated. Edible grade colours and suitable printing ink shall be used for such printing.
6.2. After printing, tablets and capsules shall be approved by Quality Control before release for packaging or sale.
7. Packaging (Strip and Blister)
7.1. Care shall be taken when using automatic tablet and capsule counting, strip and blister packaging equipment to ensure that all ‘rogue’ tablets, capsules or foils from packaging operation are removed f\before a new packaging operation is commenced. There shall be an independent recorded check of the equipment before a new batch of tablets or capsules is handled.
7.2. Uncoated tablets shall be packed on equipment designed to minimize the risk of cross-contamination. Such packaging shall be carried out in an isolated area when potent tablets or Beta-Iactum containing tablets are being packed.
7.3. The strips coming out of the machine shall be inspected for defects such as misprint, cuts on the foil, missing tablets and improper sealing.
7.4. Integrity of individual packaging strips and blisters shall be subjected to vacuum test periodically to ensure leak proofness of each pocket strip and blister and records maintained.
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PART I-C SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL LIQUIDS
(SYRUPS, ELIXIRS, EMULSIONS AND SUSPENSIONS)
Note :- The General Requirements as given in Part I of this Schedule relating to Requirements of Good Manufacturing Practices for Premises and Materials for pharmaceutical products shall be complied with, mutates mutandis, for the manufacture of (Syrups, Elixirs, Emulsions and Suspensions). In addition to these requirement, the following Specific Requirements shall also be followed, namely:-
1. Building and Equipment.
1.1. The premises and equipment shall be designed, constructed and maintained to suit the manufacturing of Oral Liquids. The layout and design of the manufacturing area shall strive to minimize the risk of cross-contamination and mix-ups.
1.2. Manufacturing area shall have entry through double door airlock facility. It shall be fly proof by use of ‘fly catcher’ and/or ‘air curtain’.
1.3. Drainage shall be of adequate size and have adequate traps, without open channels and design shall be such as to prevent back flow. Drains shall be shallow to facilitate cleaning and disinfecting.
1.4. The production area shall be cleaned and sanitized at the end of every production process.
1.5. Tanks, containers, pipe work and pumps shall be designed and installed so that they can be easily cleaned and sanitized. Equipment design shall be such as to prevent accumulation of residual microbial growth or cross-contamination.
1.6. Stainless steel or any other appropriate material shall be used for parts of equipments coming in direct contact with the products. The use of glass apparatus shall be minimum.
1.7. Arrangements for cleaning of containers, closures and droppers shall be made with the help of suitable machines/devices equipped with the high pressure air, water and steam jets.
1.8. The furniture used shall be smooth, washable and made of stainless steel.
2. Purified Water.
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2.1. The chemical and microbiological quality of purified water used shall be specified and monitored routinely. The microbiological evaluation shall include testing for absence of pathogens and shall not exceed 100 cfu/ml (as per Appendix 12.5 of IP 1996.)
2.2. There shall be a written procedure for operation and maintenance of the purified water system. Care shall be taken to avoid the risk of microbial proliferation with appropriate methods like re-circulation, use of UV treatment, treatment with heat and sanitizing agent. After any chemical sanitisation of the water systems, a flushing shall be done to ensure that the sanitizing agent has been effectively removed.
3. Manufacturing
3.1. Manufacturing personnel shall wear non-fiber shedding clothing to prevent contamination of the product.
3.2. Materials likely to shed fiber like gunny bags, or wooden pallets shall not be carried into the area where products or cleaned-containers are exposed.
3.3. Care shall be taken to maintain the homogenecity of emulsion by use of appropriate emulsifier and suspensions by use of appropriate stirrer during filling. Mixing and filling processes shall be specified and monitored. Special care shall be taken at the beginning of the filling process, after stoppage due to any interruption and at the end of the process to ensure that the product is uniformly homogenous during the filling process.
3.4. The primary packaging area shall have an air supply which is filtered through 5 micron filters. The temperature of the area shall not exceed 30 degrees centigrade.
3.5. When the bulk product is not immediately packed, the maximum period of storage and storage conditions shall be specified in the Master Formula. The maximum period of storage time of a product in the bulk stage shall be validated.
PART I-D
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF TOPICAL PRODUCTS i.e. EXTERNAL PREPARATIONS (CREAMS, OINTMENTS, PASTES, MULSIONS, LOTIONS, SOLUTIONS, DUSTING POWDERS AND IDENTICAL PRODUCTS)
Note: - The General Requirements as given in Part I of this Schedule relating to Requirements of Good Manufacturing Practices for Premises and Materials for pharmaceutical products shall be complied with, mutates mutandis, for the manufacture of Topical Products i.e. External preparations (Creams, Ointments, Pastes, Emulsions, Lotions, Solutions, Dusting powders and identical products used for external applications). In
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addition to these requirements, following Specific Requirements shall also be followed, namely: -
1. The entrance to the area where topical products are manufactured should bethrough a suitable airlock. Outside the airlock, insectocutors shall be installed.
2. The air to this manufacturing area shall be filtered through at least 20µ air filters and shall be air-conditioned. The area shall be ventilated.
3. The area shall be fitted with an exhaust system of suitable capacity to effectively remove vapours, fumes, smoke, floating dust particles.
4. The equipment used shall be designed and maintained to prevent the product from being accidentally contaminated with any foreign matter or lubricant.
5. No rags or dusters shall be used in the process of cleaning or drying the process equipment or accessories used.
6. Water used in compounding shall be Purified Water IP.
7. Powders, wherever used, shall be suitably sieved before use.
8. Heating vehicles and a base like petroleum jelly shall be done in separate mixing area in suitable stainless steel vessels, using steam, gas, electricity, solar energy, etc.
9. A separate packing section may be provided for primary packaging of the products.
PART I-E SPECIFIC REQUIREMENTS FOR MANUFACTURE OF
METERED-DOSE-INHALERS (MDI)
Note: - The General Requirements as given in Part I of this Schedule relating to Requirements of Good Manufacturing Practices for Premises and Materials for pharmaceutical products shall be complied with, mutates mutandis, for the manufacture of Metered-Dose-Inhalers (MDI). In addition to these requirements, the following Specific Requirements shall also be followed, namely: -
1. General
Manufacture of Metered-Dose-Inhalers shall be done under conditions which shall ensure minimum microbial and particulate contamination. Assurance of the quality of components and the bulk product is very important. Where medicaments are in suspended state, uniformity of suspension shall be established.
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2. Building and Civil Works
2.1. The building shall be located on a solid foundation to reduce risk of cracking walls and floor due to the movement of equipment and machinery.
2.2 All building surfaces shall be impervious, smooth and non-shedding. Flooring shall be continuous and provided with a cove between the floor and the wall as well as the wall to the ceiling. Ceiling shall be solid, continuous and covered to walls. Light fittings and air-grills shall be flush with the ceiling. All service lines requiring maintenance shall be erected in such a manner that these accessible from outside the production area.
2.3. The manufacturing area shall be segregated into change rooms for personnel, container preparation area, bulk preparation and filling area, quarantine area and spray testing and packing areas.
2.4. Secondary change rooms shall be provided for operators to change from factory clothing to special departmental clothing before entering the manufacturing and filling area.
2.5. Separate area shall be provided for de-cartoning of components before they are air washed.
2.6. The propellants used for manufacture shall be delivered to the manufacturing area distribution system by filtering them through 2µ filters. The bulk containers of propellants shall be stored, suitably identified, away from the manufacturing facilities.
3. Environmental Conditions
3.1. Where products or clean components are exposed, the area shall be supplied with filtered air of Grade C.
3.2. The requirements of temperature and humidity in the manufacturing area shall be decided depending on the type of product and propellants handled in the facility. Other support area shall have comfort levels of temperature and humidity.
3.3. There shall be a difference in room pressure between the manufacturing area and the support areas and the differential pressure shall be not less than 15 Pascals (0.06 inches or 1.5mm water gauge).
3.4. There shall be a written schedule for the monitoring of environmental conditions. Temperature and humidity shall be monitored daily.
4. Garments
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4.1. Personnel in the manufacturing and filling section shall wear suitable single-piece- garment made out of non-shedding, tight weave material. Personnel in support areas shall wear clean factory uniforms.
4.2. Gloves made of suitable material having no interaction with the propellants shall be used by the operators in the manufacturing and filling areas. Preferably, disposable gloves shall be used.
4.3. Suitable department-specific personnel protective equipment like footwear and safety glasses shall be used wherever hazard exists.
5. Sanitation
5.1. There shall be written procedures for the sanitation of the MDI manufacturing facility. Special care should be taken to handle residues and rinses of propellants.
5.2. Use of water for cleaning shall be restricted and controlled. Routinely used disinfectants are suitable for sanitizing the different areas. Records of sanitation shall be maintained.
6. Equipment.
6.1. Manufacturing equipment shall be of closed system. The vessels and supply lines shall be of stainless steel.
6.2. Suitable check weights, spray testing machines and labeling machines shall be provided in the department.
6.3. All the equipment shall be suitably calibrated and their performance validated on receipt and thereafter periodically.
7. Manufacture.-
7.1. There shall be approved Master Formula Records for the manufacture of metered close inhalers. All propellants, liquids and gases shall be filtered through 2µ filters to remove particles.
7.2 The primary packing material shall be appropriately cleaned by compressed air suitably filtered through 0.2µ filter. The humidity of compressed air shall be controlled as applicable.
7.3. The valves shall be carefully handled and after de-cartoning, there shall be kept in clean, closed containers in the filling room.
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7.4. For suspensions, the bulk shall be kept stirred continuously.
7.5. In-process controls shall include periodical checking of weight of bulk formulation filled in the containers. In a two-shot-filling process (liquid filling followed by gaseous filling), it shall be ensured that 100% check on weight is carried out.
7.6. Filled containers shall be quarantined for a suitable period established by the manufacturer to detect leaking containers prior to testing, labeling and packing.
8. Documentation-
8.1. In addition to the routine good manufacturing practices documentation, manufacturing records shall show the following additional information:-
(1) Temperature and humidity in the manufacturing area. (2) Periodic filled weights of the formulation. (3) Records of rejections during on line check weighing. (4) Records of rejection during spray testing.
PART I-F SPECIFIC REQUIREMENTS OF PREMISES, PLANT AND MATERIALS FOR MANUFACTURE OF
ACTIVE PHARMACEUTIAL INGREDIENTS (BULK DRUGS).
Note : The General Requirements as given in Part I of this Schedule relating to Requirements of Good Manufacturing Practices for premises and Materials for pharmaceutical products shall be complied with, mutates mutandis, for the manufacture of active pharmaceutical ingredients (Bulk Drugs). In addition to these requirements, the following Specific Requirements shall also be followed, namely: -
1. Building and Civil Works. -
1.1. Apart from the building requirements contained Part-I, General note, the active pharmaceutical ingredients facilities for manufacture of hazardous reactions, Beta-Lactum antibiotics. Steroids and Steroidal Hormones / Cytotoxic substances shall be provided in confined areas to prevent contamination of the other drugs manufactured.
1.2. The final stage of preparation of a drug, like isolation / filtration / drying / milling / sieving and packing operations shall be provided with air filtration systems including pre- filters and finally with a 5 micron filter. Air handling systems with adequate number of air changes per hour or any other suitable system to control the air borne contamination shall be
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provided. Humidity / Temperature shall also be controlled for all the operations wherever required.
1.3. Air filtration systems including pre-filters and particulate matter retention air filters shall be used, where appropriate, for air supplies to production areas. If air is re-circulated to production areas, measures shall be taken to control re-circulation of floating dust particles from production. In areas where air contamination occurs during production, there shall be adequate exhaust system to control contaminants.
1.4. Ancillary area shall be provided for Boiler-house. Utility areas like heat exchangers, chilling workshop, store and supply of gases shall also be provided.
1.5. For specified preparation like manufacture of sterile products and for certain antibiotics, sex hormones, cytotoxic and oncology products, separate enclosed areas shall be designed. The requirements for the sterile active pharmaceutical ingredient shall be in line with the facilities required for formulation to be filled aseptically.
2. Sterile Products. - Sterile active pharmaceutical ingredient filled aseptically shall be treated as formulation from the stage wherever the process demands like crystallization, lyophilisation, filtration etc. all conditions applicable to formulations that are required to be filled aseptically shall apply mutates mutandis for the manufacture of sterile active pharmaceutical ingredients involving stages like filtration crystallization and lyophilisation.
3. Utilities / Services. - Equipment like chilling plant, boiler, heat exchangers, vacuum and gas storage vessels shall be serviced, cleaned, sanitized and maintained at appropriate intervals to prevent mal-functions or contamination that may interfere with safety, identity, strength, quality or purity of the drug product.
4. Equipment Design, Size and Location. -
4.1. Equipment used in the manufacture, processing, packing or holding of an active pharmaceutical ingredient shall be of appropriate design, adequate size and suitably located to facilitate operations for its intended use and for its cleaning and maintenance.
4.2. If the equipment is used for different intermediates and active pharmaceutical ingredients, proper cleaning before switching from one product to another becomes particularly important. If cleaning of a specific type of equipment is difficult, the equipment may need to be dedicated to a particular intermediate or active pharmaceutical ingredient.
4.3. The choice of cleaning methods, detergents and levels of cleaning shall be defined and justified. Selection of cleaning agents (e.g. solvents) should depend on :
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(a) the suitability of the cleaning agent to remove residues of raw materials, intermediates, precursors, degradation products and isomers, as appropriate.
(b) whether the cleaning agent leaves a residue itself, (c) compatibility with equipment construction materials like centrifuge /
filtration, dryer / fluid bed dryer, rotocone proton dryer, vacuum dryer, frit mill, multi-mill / jet mills / sewetters cut sizing;
(d) test for absence of intermediate or active pharmaceutical ingredient in the final rinse.
4.4. Written procedures shall be established and followed for cleaning and maintenance of equipment, including utensils used in the manufacture, processing, packing or holding of active pharmaceutical ingredients. These procedures shall include but should not be limited to the following :
(a) assignment of responsibility for cleaning and maintaining equipment; (b) maintenance and cleaning program schedules, including where appropriate,
sanitizing schedules; (c) a complete description of the methods and materials used to clean and
maintain equipment, including instructions for de-assembling and re- assembling each article of equipment to ensure proper cleaning and maintenance.;
(d) removal or obliteration of previous batch identification; (e) protection of clean equipment from contamination prior to use; (f) inspection of equipment for cleanliness immediately before use; (g) establishing the maximum time that may elapse between completion of
processing and equipment cleaning as well as between cleaning and equipment reuse.
4.5. Equipment shall be cleaned between successive batches to prevent contamination and carry-over of degraded material or contaminants unless otherwise established by validation.
4.6. As processing approaches the final purified active pharmaceutical ingredient, it is important to ensure that incidental carry over between batches does not have adverse impact on the established impurity profile. However, this does not generally hold good for any biological, active pharmaceutical ingredient where many of the processing steps are accomplished aseptically and where it is necessary to clean and sterilize equipment between batches.
5. In-Process Controls. -
5.1. In-process control for chemical reactions may include the following: (a) reaction time or reaction completion; (b) reaction mass appearance, clarity, completeness or pH solutions;
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(c) reaction temperature (d) concentration of a reactant; (e) assay or purity of the product (f) process completion check by TLC / any other means.
5.2. In-process control for physical operations may include the following: (a) appearance and colour; (b) uniformity of the blend; (c) temperature of a process; (d) concentration of a solution; (e) processing rate or time; (f) particle size analysis; (g) bulk/tap density; (h) pH determination (i) moisture content,
6. Product Containers and Closures
6.1. All containers and closures shall comply with the pharmacopoeial or any other requirement, suitable sampling methods, sample sizes, specifications, test methods, cleaning procedures and sterilization procedures, when indicated, shall be used to assure that containers, closures and other component parts of drug packages are suitable and are not reactive, additive, adsorptive or leachable to an extent that significantly affects the quality or purity of the drug.
6.2. The drug product container shall be tested or re-examined as appropriate and approved or rejected and shall be identified and controlled under a quarantine system designed to prevent their use in manufacturing or processing operations for which these are unsuitable.
6.3 Container closure system shall provide adequate protection against foreseeable external factors in storage / transportation and use that may cause deterioration or contamination of the active pharmaceutical ingredient.
6.4. Bulk containers and closures shall be cleaned and, where indicated by the nature of the active pharmaceutical ingredient, sterilized to ensure that they are suitable for their intended use.
6.5. The container shall be conspicuously marked with the name of the product and the following additional information concerning :
(a) quality and standards, if specified; (b) manufacturing licence number/drug master file number (whichever
applicable), batch number;
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(c) date of manufacture and date of expiry; (d) method for container disposal (label shall give the methodology, if
required); (e) storage conditions, if specified and name and address of the
manufacturer, if available.
6.6. Areas for different operation of active pharmaceutical ingredients (bulk drugs) section shall have appropriate area which may be suitably partitioned for different operations.
PART- II REQUIREMENTS OF PLANT AND EQUIPMENT
1. External Preparations. - The following equipments are recommended for the manufacture of ‘External
preparations’ i.e. Ointments, Emulsion, Lotions, Solutions, Pastes, Creams, Dusting powders and such identical products used for external applications whichever is applicable, namely :-
(1) Mixing and storage tanks (stainless steel), (2) Jacketted Kettle (steam, gas or electrically heated), (3) Mixer (electrically operated) (4) Planetary mixer (5) A colloid mill or a suitable emulsifier. (6) A triple roller mill or an ointment mill. (7) Liquid filling equipment (electrically operated). (8) Jar or tube filling equipment (electrically operated)
Area. - (1) A minmum area of thirty square meters for basic installation of ten square meters for Ancillary area is recommended.
(2) Areas for formulations meant for external use and internal use shall be separately provided to avoid mix-up.
2. Oral Liquid Preparations. -
The following equipments are commended for the manufacture of oral/internal use preparations i.e. Syrups, Elixirs, Emulsions and suspensions, whichever is applicable, namely: -
(1) Mixing and storage tanks (stainless steel), (2) Jacketted Kettle / Stainless steel tank (steam, gas or electrically heated). (3) Portable stirrer (electrically operated) (4) A colloid mill or suitable emulsifier (electrically operated) (5) Suitable filtration equipment (electrically operated)
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(6) Semi-automatic/automatic bottle filling machine (7) Pilfer proof cap sealing machine. (8) Water distillation unit or deioniser (9) Clarity testing inspection units.
Area. - A minimum area of thirty square meters for basic installation and ten square meters for Ancillary area is recommended.
3.Tablets
The Tableting section shall be free from dust and floating particles and may be air- conditioned. For this purpose, each tablet machine shall be isolated into cubicles and connected to a vacuum dust collector or an exhaust system. For effective operations, the tablet production department shall be divided into four distinct and separate sections as follows: -
(a) Mixing, Granulation and Drying section. (b) Tablet compression section. (c) Packaging section (strip/blister machine wherever required). (d) Coating section (wherever required).
3.1. The following electrically operated equipments are recommended for the manufacture of compressed tablets and hypodermic tablets, in each of the above sections, namely: -
(a) Granulation-cum-Drying section
(1) Disintegrator and sifter (2) Powder mixer (3) Mass mixer/Planetary mixer/Rapid mixer granulator. (4) Granulator (5) Thermostatically controlled hot air oven with trays (preferably mounted on
a trolley)/Fluid bed dryer. (6) Weighing machines.
(b) Compression section.
(1) Tablet compression machine, single/multi punch/rotatory. (2) Punch and dies storage cabinets. (3) Tablet de-duster (4) Tablet Inspection unit/belt. (5) Dissolution test apparatus (6) In-process testing equipment like single pan electronic balance, hardness
tester, friability and disintegration test apparatus.
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(7) Air-conditioning and dehumidification arrangement (wherever necessary)
(c) Packaging section.
(1) Strip/blister packaging machine. (2) Leak test apparatus (vacuum system) (3) Tablet counters (wherever applicable) (4) Air-conditioning and dehumidification arrangement (whereever applicable).
Area. - A minimum area of sixty square meters for basic installation and twenty square meters for Ancillary area is recommended for un-coated tablets.
(d) Coating section,
(1) Jacketted kettle (steam, gas or electrically heated for preparing coating suspension).
(2) Coating pan (stainless steel) (3) Polishing pan (where applicable) (4) Exhaust system (including vacuum dust collector) (5) Air-conditioning and dehumidification arrangement. (6) Weighing balance.
3.2. The Coating section shall be made dust free with suitable exhaust system to remove excess powder and fumes resulting from solvent evaporation. It shall be air-conditioned and dehumidified wherever considered necessary.
Area. - A minimum additional area of thirty square meters for coating section for basic installation and ten square meters for Ancillary area is recommended.
Separate area and equipment for mixing, granulation, drying, tablet compression, coating and packing shall be provided for Penicillin group of drugs on the lines indicated above. In case of operations involving dust and floating particles, care shall be exercised to avoid cross- contamination.
3.3. The manufacture of Hypodermic tablets shall be conducted under aseptic conditions in a separate air-conditioned room, the walls of which shall be smooth and washable. The granulation, tableting and packing shall be done in this room.
3.4. The manufacture of effervescent and soluble/dispersible tablets shall be carried out in air-conditioned and dehumidified areas.
(4) Powders
The following equipment is recommended for the manufacture of powders, namely:-
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(1) Disintegrator (2) Mixer (electrically operated) (3) Sifter. (4) Stainless steel vessels and scoops of suitable sizes. (5) Filling equipment (electrically operated). (6) Weighing balance.
In the case of operation involving floating particles of fine powder, suitable exhaust system shall be provided. Workers should be provided with suitable masks during operation.
Area. - A minimum area of thirty square meters is recommended to allow for the basic installations. Where the actual blending is to be done on the premises, an additional room shall be provided for the purpose.
(5)Capsules
For the manufacture of capsules, separate enclosed area suitably air-conditioned and dehumidified with an airlock arrangement shall be provided. The following equipment is recommended for filling Hard Gelatin Capsules, namely: -
(1) Mixing and blending equipment (electrically or power driven). (2) Capsules filling units (preferably semi automatic or automatic filling machines). (3) Capsules counters (wherever applicable) (4) Weighing balance. (5) Disintegration test apparatus. (6) Capsule polishing equipment.
Separate equipment and, filling and packaging area shall be provided in penicillin and non-penicillin sections. In case of operations involving floating particles of fine powder, a suitable exhaust system shall be provided. Manufacture and filling shall be carried out in air- conditioned area. The room shall be dehumidified.
Area. - A minimum area of twenty-five square meters for basic installation and ten square meters for Ancillary area each for penicillin and non-penicillin sections is recommended.
(6)Surgical Dressing
The following equipment is recommended for the manufacture of Surgical Dressings other than Absorbent Cotton Wool, namely:-
(1) Rolling machine (2) Trimming machine (3) Cutting equipment.
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(4) Folding and pressing machine for gauze. (5) Mixing tanks for processing medicated dressing. (6) Hot air dry oven. (7) Steam sterilizer or dry heat sterilizer or other suitable equipment. (8) Work tables/benches for different operations.
Area. - A minimum area of thirty square meters is recommended to allow for the basic installations. In case medicated dressings are to be manufactured, another room with a minimum area of thirty square meters shall be provided.
(7) Ophthalmic Preparations.
For the manufacture of Ophthalmic preparations, separate enclosed areas with airlock arrangement shall be provided. The following equipment is recommended for the manufacture under aseptic conditions of Eye-Ointment, Eye-Lotions and other preparations for external use, namely
(1) Thermostatically controlled hot air ovens (preferably double ended). (2) Jacketted kettle/stainless steel tanks (steam, gas or electrically heated). (3) Mixing and storage tanks of stainless steel/Planetary mixer. (4) Colloid mill or ointment mill. (5) Tube filling and crimping equipment (semi-automatic or automatic filling
machines). (6) Tube cleaning equipment (air jet type), (7) Tube washing and drying equipment, if required (8) Automatic vial washing machine. (9) Vial drying oven.
(10) Rubber bung washing machine. (11) Sintered glass funnel, Seitz filter and filter candle (preferably cartridge and
membrane filters). (12) Liquid filling equipment (semi-automatic or automatic filling machines). (13) Autoclave (preferably ventilator autoclave). (14) Air conditioning and dehumidification arrangement (preferably centrally air-
conditioned and dehumidification system). (15) Laminar airflow units.
Area. - (1) A minimum area of twenty-five square meters for basic installation and ten square meters for Ancillary area is recommended. Manufacture and filling shall be carried out in air-conditioned areas under aseptic conditions. The rooms shall be further dehumidified as considered necessary if preparations containing antibiotics are manufactured.
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(2) Areas for formulations meant for external use and internal use shall be separately provided to avoid mix up.
(8) Pessaries and Suppositories
(i) The following equipment is recommended for manufacture of Pessaries and Suppositories, namely: -
(1) Mixing and pouring equipment (2) Moulding equipment. (3) Weighing devices.
Area. - A minimum area of twenty square meters is recommended to allow for the basic installation.
(iii) In the case of Pessaries manufactured by granulation and compression, the requirements as indicated under “Item 3 of Tablet”, shall be provided.
9. Inhalers and Vitralle
The following equipment is recommended for manufacture of inhalers and vitrallae, namely: -
(1) Mixing equipment. (2) Graduated delivery equipment for measurement of the medicament during filling. (3) Sealing equipment.
Area. - An area of minimum twenty square meters is recommended for the basic installations.
10. Repacking of Drugs and Pharmaceutical Chemicals.
The following equipment is recommended for repacking of drugs and pharmaceuticals chemicals, namely:-
(1) Powder disintegrator (2) Powder sifter (electrically operated) (3) Stainless steel scoops and vessels of suitable sizes (4) Weighing and measuring equipment. (5) Filling equipment (semi-automatic / automatic machines). (6) Electric sealing machine.
Area- An area of minimum thirty square meters is recommended for the basic installation. In case of operations involving floating particles of fine powder, a suitable exhaust system shall be provided.
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11. Parenteral Preparations
The whole operation of manufacture of parenteral preparations (small volume injectables and large volume parenterals) in glass and plastic containers may be divided into the following separate areas/rooms, namely: -
11.1 Parenteral preparations in glass containers,-
(1) Water management area: this includes water treatment and storage (2) Containers and closures preparation area: This includes washing and drying of
ampoules, vials, bottles and closures. (3) Solution preparation area: This includes preparation and filtration of solution. (4) Filling, capping and sealing area: This includes filling and sealing of ampoules
and/or filling, capping and sealing of vials and bottles. (5) Sterilization area (6) Quarantine area (7) Visual inspection area (8) Packaging area
The following equipment is recommended for different above-mentioned areas, namely: -
(a) Water management area, -
(1) De-ionised water treatment unit (2) Distillation (multi-column with heat exchangers) unit. (3) Thermostatically controlled water storage tank. (4) Transfer pumps. (5) Stainless steel service lines for carrying water into user areas.
(b) Containers and closures preparation area, -
(1) Automatic rotary ampoule/vial/bottle washing machine having separate air, water distilled water jets.
(2) Automatic closures washing machine, (3) Storage equipment for ampoules, vials, bottles and closures. (4) Dryer/sterilizer (double ended) (5) Dust proof storage cabinets. (6) Stainless steel benches/stools.
(c) Solution preparation area. –
(1) Solution preparation and mixing stainless steel tanks and other containers.
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(2) Portable stirrer. (3) Filtration equipment with cartridge and membrane filters/bacteriological filters. (4) Transfer pumps. (5) Stainless steel benches/stools
(d) Filling, capping and sealing area, -
(1) Automatic ampoule/vial/bottle filling, sealing and capping machine under laminar air flow workstation.
(2) Gas line (Nitrogen, Oxygen, Carbon dioxide) wherever required. (3) Stainless steel benches / stools
(e) Sterilization area, -
(1) Steam sterilizer preferably with computer control for sterilization cycle along with trolley sets for loading/unloading containers before and after sterilization).
(2) Hot air sterilizer (preferably double ended). (3) Pressure leak test apparatus.
(f) Quarantine area. –
(1) Storage cabinets. (2) Raised platforms/steel racks.
(g) Visual inspection area, - (1) Visual inspection units (preferably conveyor belt type and composite white and
black assembly supported with illumination). (2) Stainless steel benches/stools.
(h) Packaging area. -
(1) Batch coding machine (preferably automatic) (2) Labelling unit (preferably conveyor belt type) (3) Benches/stools
Area. - (1) A minimum area of one hundred and fifty square meters for the basic installation and an Ancillary area of one hundred square meters for Small Volume Injectables are recommended. For Large Volume Parenterals, an area of one hundred and fifty square meters each for the basic installation and for Ancillary area is recommended. These areas shall be partitioned into suitable enclosures with airlock arrangements.
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(2) Areas for formulations meant for external use and internal use shall be separately provided to avoid mix up.
(3) Packaging materials for large volume parenteral shall have a minimum area of 100 square meters.
11.2 Parenteral preparations in plastic containers by Form-Fill-Seal/Blow, Fill-Seal Technology. -The whole operation of manufacture of large volume parenteral preparations in plastic containers including plastic pouches by automatic (all operations in one station) Form- Fill-Seal machine or by semi-automatic blow moulding, filling-cum-sealing machine may be divided into following separate areas/rooms, namely: -
(1) Water management area (2) Solution preparation area (3) Containers moulding-cum filling and sealing area (4) Sterilization area (5) Quarantine area (6) Visual inspection area (7) Packing area
The following equipment is recommended for different above mentioned areas namely: -
(a) Water management area, -
(1) De-ionised water treatment unit (2) Distillation unit (multi column with heat exchangers) (3) Thermostatically controlled water storage tank (4) Transfer pumps (5) Stainless steel service lines for carrying water into user areas.
(b) Solution preparation area, -
(1) Solution preparation and storage tanks. (2) Transfer pumps (3) Cartridge and membrane filters.
(i) Container moulding-cum-filling and sealing area, -
(1) Sterile Form-Fill-Seal machine (all operations in one station with built-in laminar air flow workstation having integrated container output conveyor belt through pass box).
(2) Arrangement for feeding plastic granules through feeding-cum-filling tank into the machine.
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(j) Sterilization area, - Super heated steam sterilizer (with computer control for sterilization cycle along with trolley sets for loading/unloading containers for sterilization).
(k) Quarantine area, - Adequate number of platforms/racks with storage system.
(l) Visual inspection area, - Visual inspection unit (with conveyor belt and composite
(m) Packaging area, -
(1) Pressure leak test apparatus (pressure belt or rotating disc type) (2) Batch coding machine (preferably automatic) (3) Labelling unit (preferably conveyor belt type).
Area. - (1) A minimum area of two hundred and fifty square meters for the basic installation of an Ancillary area of one hundred and fifty square meters for large volume parenteral preparations in plastic containers by Form-Fill-Seal technology is recommended. These areas shall be partitioned into suitable enclosures with airlock arrangements.
(2) Areas for formulations meant for external use and internal use shall be separately provided to avoid mix up.
(3) Packaging materials for large volume parenteral shall have a minimum area of 100 square meters.]
*SCHEDUE M-I [See Rule 85-E (2)]
1. Requirements of factory premises for manufacture of Homoeopathic preparations. -
(A) Location and surroundings. - The factory shall be situated in a place which shall not be adjacent to an open sewage drain, public lavatory or any factory which produces a disagreeable or obnoxious odour or fumes or large quantities of soot, dust or smoke. The factory shall be located in a sanitary place, remove from filthy surroundings.
(B) Buildings. - The part of the building used for manufacturing shall not be used for a sleeping place and no sleeping place adjoining to it shall communicate therewith except through open air or through an intervening open space. The walls of the room in which manufacturing operations are carried out shall, upto a height of six feet from the floor, be smooth, waterproof and shall be capable of being kept clean. The flooring shall be smooth, even and washable and shall be such as not to permit retention or accumulation of dust. There shall be no chinks or crevices in the walls or floor.
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The building used for the factory shall be constructed so as to permit production under hygienic conditions laid down in the Factories Act, 1948 (63 of 1948).
(C) Water Supply. - The water used in manufacture shall be pure and drinkable quality, free from pathogenic microorganisms.
(D) Disposal of waste. - There should be adequate arrangement for disposal of wastewater and other residues from the laboratory.
The rooms should be airy and clean and the temperature of the room should be moderately comfortable.
(E) Health, Clothing and Sanitary requirement of the Staff. - All workers shall be free from contagious or obnoxious disease. Their clothing shall consist of a white or coloured uniform suitable to the nature of the work and the climate, and shall be clean. Adequate facilities for personal cleanliness, such as clean towels, soap and hand scrubbing brushes, shall be provided separately for each sex. The workers shall be required to wash and change into clean footwear before entering the rooms where the manufacturing operations are carried on. Workers shall be required to wear either a clean cap or a suitable headgear so as to avoid any possibility of contamination by air or perspiration.
(F) Medical services. - The manufacturer shall provide adequate facilities for First Aid, Medical inspection of workers at the time of employment and periodically check-up thereafter at least once a year.
(G) Working benches. - Working benches shall be provided for carrying out operations such as filling, labeling, packing etc. such benches shall be fitted with smooth, impervious tops capable of being washed.
(H) Container management. - Where operations involving use of containers such as bottles, phials and jars are conducted, there shall be adequate arrangements separated from potentisation chamber for washing, cleaning and drying such containers, with suitable equipment for the purpose. Wherever these are attended manually adequate precaution of perfection in respect of cleanliness and avoidance of pollutants shall be taken.
___________________________________________________________________________ * Ins. by G.O.I Notification G.S.R. No. 507(E) dt 12-06-1987 w.e.f. 12.06.1987
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2. Requirements of Plant and Equipment. -
(A) Mother tinctures. External tinctures and Mother solution section. - The following plant and equipment shall be provided namely: -
(i) Disintegrator (ii) Sieved Separator (iii) Balances and fluid measures (iv) Chopping boards and knives. (v) Macerators with lids. (vi) Percolators with lids and regulated discharge. (vii) Moisture determination apparatus or other suitable arrangement. (viii) Filtering arrangement (ix) Mixing vessels and suitable non-metallic storage containers. (x) Portable stirrers. (xi) Water still
Note: - (1) As for as possible metal contacts may be avoided once the drug is processed.
(2) An area of 55 sq. meters is recommended for basic installations.
(3) Adequate separate storage facility should be provided for raw material quarantine, storage and bonded room for alcohol were applicable.
(4) Separate and suitable storage facility should be provided for fresh herbs and odorous raw materials.
(5) Adequate laboratory facility shall be provided for testing of raw material and finished products,
(a) Potentisation Section. - (1) the following arrangements are recommended for container for closure preparation
section namely: - (i) Washing tanks with suitable brushing arrangement manual or mechanical. (ii) Purified Water rinsing tank (iii)Closure macerating or washing tanks. (iv)Drying chambers.
An area of 20 sq. meters is recommended for basic installation.
(2) The following arrangements are recommended for potency preparation section, namely: -
(i) Working tables with washable top. (ii) Facilities for separate storage of different grades of back potencies.
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(iii)Suitable measuring devices for discharge of drug and diluent in potentisation vial,
(iv)Potentiser with counter or suitable manual arrangement. Note: - (1) Different droppers shall be used for different drugs potencies.
(3) All measuring devices shall be of metric system and be made of glass and shall be free from metallic contents.
(4) It is desired that glass droppers etc. intended for re-use after cleaning should be sterilized by autoclave or heating in a hot air oven.
(5) Plastics, rubber tubes, bulks etc. coming in contact with tinctures or back potencies should not be re-used for other tincture and potencies.
(6) Method of potentisation will be adopted as specified in Homoeopathic Pharmacopoeia of India Vol. I (3) Triturating, Tableting and Pill/Globules section -
(3) The following arrangement are recommended: - (i) Triturating machine for suitable device (iii) Disintegrator (iv) Mass Mixer (v) Granulator (vi) Oven (vii) Tableting punches or machines (vii) Kettle (Steam/gas/electrically heated) for preparation solution. (viii) Dryers (ix) Sieved separator, tablet counters and balances.
Note: - Tablet section shall be free from dust and floating particles. An area of 55 sq. meters is recommended for basis installations
(4) Ointments and lotion section. The following arrangements are recommended namely: -
(i) Mixing tank (ii) Kettle (Steam, gas or electrically heated). (iii)Suitable powder mixer (iv)Ointment mill (v)Filling equipment or arrangement.
An area of 20 sq. meters is recommended for basic installation.
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(5) Syrups and tonics: - The following arrangements are recommended namely:-
(i) Mixing and storage tank (ii) Potable mixer (iii) Filtering equipment (iv) Water still / Deioniser (v) Filling and sealing equipment. An area of 20 sq. meters is recommended for basic installations.
(6) Ophthalmic Preparations: The following equipment is recommended for manufacture under aseptic conditions of Eye-Ointments, Eye-Drops, Eye-lotion and other preparations for external use, namely: -
(i) Hot air even electrically heated with thermostatic control. (ii) Colloid mill or ointment mill. (iii) Kettle (gas or electrically heated) with suitable mixing arrangement. (iv) Tube filling equipment. (v) Mixing and storage tanks of stainless steel or of other suitable material. (vi) Sintered glass funnel, Seitz filter or filter candle. (vii) Liquid filling equipment (viii) Autoclaves
Adequate precaution should be taken to ensure that the finished product is sterile. An area of 20 Sq. meters is recommended for basic installations.
(7) Adequate arrangements for space and equipment should made for labeling and packing.
*[SCHEDULE M-II [See Rule 139]
REQUIREMENT OF FACTORY PREMISESFOR MANUFACTURE OF COSMETICS.
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1. GENERAL REQUIREMENTS
(A) Location and surroundings. - The factory shall be located in a sanitary place and hygienic conditions shall be maintained in the premises. Premises shall not be used for residence or be interconnected with residential area. It shall be well ventilated and clean.
(B) Buildings. - The buildings used for the factory shall be constructed so as to permit production under hygienic conditions and not to permit entry of insects, rodents, files, etc. The walls of the room in which manufacturing operations are carried out, shall up to a height of six feet from the floor, be smooth, waterproof and capable of being kept clean. The flooring shall be smooth, even and washable and shall be such as not to permit retention or accumulation of dust.
(C) Water supply: - The water used in manufacture shall be of potable quality.
(D) Disposal of water. - Suitable arrangements shall be made for disposal of wastewater.
(E) Health, clothing and sanitary requirements of the staff. - All workers shall be free from contagious or infectious diseases. They shall be provided with clean uniforms, masks, headgears, and gloves wherever required. Washing facilities shall also be provided.
(F) Medical Services. - Adequate facilities for first aid shall be provided
(G)Working benches shall be provided for carrying out operations such as filling, labeling, packing, etc. such benches shall be fitted with smooth, impervious tops capable of being washed.
(H)Adequate facilities shall be provided for washing and drying of glass containers if the same are to be used for packing the product.
* Ins. by G.O.I. Notification No. GSR 723(E) dt 11-8-1992.
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II. Requirement of Plant and Equipment
The following equipment, area and other requirements are recommended for the manufacture of: -
A. Powders. - Face powder, cake make-up, compacts, face packs, masks and rouges, etc.
1. Equipment.
(a) Powder mixer of suitable type provided with a dust collector. (b) Perfume and colour blender. (c) Sifter with sieves of suitable mesh size. (d) Ball mill or suitable grinder. (e) Trays and scoops (stainless steel). (f) Filling and sealing equipment provided with dust extractor. (g) For compacts: -
(i) a separate mixer, (ii) compact pressing machine. (h) Weighing and measuring devices (i) Storage tanks.
An area of 15 square meters is recommended. The section is to be provided with adequate exhaust fans.
B. Creams, lotions, emulsions, pastes, cleansing milks, shampoos, pomade, brilliantine, shaving creams and hair-oils etc.
(a) Mixing and storage tanks of suitable materials. (b) Heating kettle – steam, gas or electrically heated. (c) Suitable agitator. (d) Colloidal mill or homogeniser (wherever necessary) (e) Triple roller mill (wherever necessary). (f) Filling and sealing equipment. (g) Weighing and measuring devices.
An area of 25 square meters is recommended.
C. Nail Polishes and Nail lacquers.
1. Equipment:
(a) A suitable mixer. (b) Storage tanks. (c) Filling machine – hand operated or power driven.
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(d) Weighing and Measuring devices.
An area of 15 square meters is recommended. The section shall be provided with flameproof exhaust system.
2. Premises: - The following are the special requirements related to Nail Polishes and Nail Lacquers: -
(a) It shall be suited in an industrial area. (b) It shall be separate from other cosmetic-manufacturing areas by metal/brick
partition up to ceiling. (c) Floors, walls, ceiling and doors shall be fireproof. (d) Smoking, cooking and dwelling shall not be permitted and no naked flame
shall be brought in the premises. (e) All electrical writing and connections shall be concealed and main electric
switch shall be outside the manufacturing area. (f) All equipment, furniture and light fittings in the section shall be flameproof. (g) Fire extinguisher like foam and dry powder and sufficient number of buckets
containing sand shall be provided. (h) All doors of the section shall open outwards.
3. Storage. - All explosive solvents and ingredients shall be stored in metal cupboards or in a separate enclosed area.
4. Manufacture:
(a) Manufacture of lacquer shall not be undertaken unless the above conditions are complied with.
(b) Workers shall be asked to wear shoes with rubber soles in the section.
5. Other requirements: - No objection certificate from the local Fire Brigade Authorities shall be furnished.
D. Lipsticks and Lip-gloss, etc.
1. Equipment
(a) Vertical mixer (b) Jacketted kettle – steam, gas or electrically heated. (c) Mixing vessel (stainless steel) (d) Triple roller mill/Ball mill. (e) Moulds with refrigeration facility. (f) Weighing and measuring devices.
An area of 15 square meters is recommended.
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E. Depilatories.
1. Equipment:
(a) Mixing tanks. (b) Mixer (c) Triple roller mill or homogeniser (where necessary). (d) Filling and sealing equipment (e) Weighing and measuring devices. (f) Moulds (where necessary)
An area of 10 square meters is recommended.
F. Preparations used for Eyes: - Such preparations shall be manufactured under strict hygienic conditions to ensure that these are safe for use.
I. Eyebrows, Eyelashes, Eyeliners, etc.
1 Equipment:
(a) Mixing tanks. (b) A suitable mixer. (c) Homogeniser (where necessary) (d) Filling and sealing equipment. (e) Weighing and measuring devices.
An area of 10 square meters is recommended.
II. Kajal and Surma 1.Equipment:
(a) Base sterilizer (b) Powder sterilizer (dry heat oven). (c) Stainless steel tanks. (d) A suitable Mixer (e) Stainless steel sieves (f) Filling and sealing arrangements. (g) Weighing and measuring devices. (h) Homogeniser (where necessary) (i) Pestle and Mortar (for Surma)
An area of 10 square meters with a separate area of 5 square meters for base sterilization is recommended.
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Other requirements for 1 and 2
(a) False ceiling shall be provided wherever required. (b) Manufacturing area shall be made fly proof. An airlock or an air curtain shall
be provided. (c) Base used for Kajal shall be sterilized by heating the base at 150 degree C for
required time in a separate enclosed area. (d) The vegetable carbon black powder shall be sterilized in a drying oven at 120
degree C for required time. (e) All utensils used for manufacture shall be of stainless steel and shall be
washed with detergent water, antiseptic liquid and again with distilled water. (f) Containers employed for ‘Kajal’ shall be cleaned properly with bactericidal
solution and dried. (g) Workers shall put on clean overalls and use hand gloves wherever necessary.
G. Aerosol.
1. Equipment: -
(a) Air-compressor (wherever necessary). (b) Mixing tanks. (c) Suitable propellant filling and crimping equipments. (d) Liquid filling unit. (e) Leak testing equipment. (f) Fire extinguisher (wherever necessary) (g) Suitable filtration equipment. (h) Weighing and measuring devices.
An area of 15 square meters is recommended.
2. Other requirements: - No objection certificate from the Local Fire Brigade Authorities shall be furnished.
H. Alcoholic Fragrance Solutions.
1. Equipment: -
(a) Mixing tanks with stirrer (b) Filtering equipment. (c) Filling and sealing equipment. (d) Weighing and measuring devices.
An area of 15 square meters is recommended.
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I. Hair Dyes.
1. Equipment:
(a) Stainless steel tanks. (b) Mixer. (c) Filling Unit (d) Weighing and measuring devices. (e) Masks, gloves and goggles.
An area of 15 square meters with proper exhaust is recommended.
J. Tooth powders and toothpastes, etc.
1.Tooth-powder in General. 1. Equipment:
(a) Weighing and measuring devices. (b) Dry mixer (powder blender) (c) Stainless steel sieves (d) Powder filling and sealing equipments.
An area of 15 square meters with proper exhaust is recommended.
2. Toothpastes.
1. Equipment:
(a) Weighing and measuring devices. (b) Kettle – steam, gas or electrically heated (where necessary) (c) Planetory mixer with de-aerator system. (d) Stainless steel tanks. (e) Tube filling equipment. (f) Crimping machine.
An additional area of 15 square meters with proper exhaust is recommended.
3.Tooth-powder (Black)
1. Equipment:
(a) Weighing and measuring devices. (b) Dry mixer powder blender. (c) Stainless steel sieves. (d) Powder filling arrangements.
An area of 15 square meters with proper exhaust is recommended. Areas for manufacturing “Black” and “White” tooth powders should be separate.
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K. Toilet Soaps.
1. Equipment: -
(a) Kettles/pans for saponification. (b) Boiler or any other suitable heating arrangement. (c) Suitable stirring arrangement. (d) Storage tanks or trays (e) Driers. (f) Amalgamator/chipping machine. (g) Mixer (h) Triple roller mill. (i) Granulator (j) Plodder (k) Cutter (l) Pressing, stamping and embossing machine (m) Weighing and measuring devices.
A minimum area of 100 square meters is recommended for the small-scale manufacture of toilet soaps.
The areas recommended above are for basic manufacturing of different categories of cosmetics. In addition to that separate adequate space for storage of raw materials, finished products, packing materials shall be provided in factory premises.1 [* * *]
Note No. I.The above requirements of the Schedule are made subject to modification at the direction of the Licensing Authority, if he is of the opinion that having regard to the nature and extent of the manufacturing operations it is necessary to relax or alter them in the circumstances of a particular case.
Note No. II. The above requirements do not include requirements of machinery, equipments and premises required for preparation of containers and closers of different categories of cosmetics. The Licensing Authority shall have the discretion to examine the suitability and adequacy of the machinery, equipments and premises for the purpose of taking into consideration of the requirements of the licence.
Note No. III. Schedule M-II specifies equipments and space required for certain categories of cosmetics only. There are other cosmetics items, viz. Attars, perfumes, etc., which are not covered in the above categories. The Licensing Authority shall, in respect of such items or ___________________________________________________________________________ The words ‘A testing laboratory shall also be provided’ were omitted by G.O.I.Notification No.G.S.R.285 (E) dt 16.07.1996.
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categories of cosmetics have the discretion to examine the adequacy of factory premises, space, plant and machinery and other requisites having regard to the nature and extent of the manufacturing operations involved and direct the licensee to carry on necessary modification in them.
Note No. IV. **[Areas for formulations meant for external use and areas for formulations meant for internal use shall be separately provided to avoid mix-up even though they are from the same category of formulations]
***[SCHEDULE M-III [See Rule 76]
REQUIREMENTS OF FACTORY PREMISES FOR MANUFACTURE OF MEDICAL DEVICES
1. GENERAL REQUIREMENTS
1.1.1. Location and surroundings. - The factory building(s) shall be located in a sanitary place and hygienic conditions shall be maintained in the premises. Premises shall be not used for residence or be interconnected with residence. It shall be well ventilated and clean.
1.1.2. Buildings. - The buildings used for the factory shall be constructed so as to permit production under hygienic conditions and not to permit entry of insets, rodents, flies etc.
The walls of the rooms in which manufacturing operations are carried out, shall be up to a height of six feet from the floor, be smooth, water proof and capable of being kept clean. The floor shall be smooth, even and washable and shall be such as not to permit retention or accumulation of dust.
1.1.3. Water supply. - The water used in manufacture shall be of potable quality.
1.1.4. Disposal of waste. - Suitable arrangements shall be made for disposal of wastewater.
1.1.5. Health, Clothing and Sanitation of workers. - All workers shall be free from contagious or infectious diseases. They shall be provided with clean uniforms, masks, headgears and gloves wherever required. Washing facilities shall also be provided.
_________________________________________________________________________ ** *** Ins. by GOI Notification No. G.S.R. 109(E), w.e.f. 22.2.1994.
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1.1.6.Medical Services. - Adequate facilities for first-aid shall be provided.
1.1.7. Workbenches shall be provided for carrying out operations such as moulding, assembling, labeling, packing etc. such benches shall be fitted with smooth impervious tops capable of being washed.
1.1.8. Adequate facilities shall be provided wherever required for cleaning, washing, drying of different containers of devices.
1.1.9. The premises shall be kept under controlled conditions of temperature and humidity so as to prevent any deterioration in the properties of materials and products due to storage and process conditions.
2. Requirements for Manufacture of Medical Devices.- The process of manufacture of medical devices shall be conducted at the licensed premises, wherever required, and shall be divided into the following separate operations/Sections:-
1) Moulding (wherever manufacture of medical devices is to start from granules). 2) Assembling (include cutting, washing and drying, sealing, packing, labeling, etc.) 3) Raw Materials. 4) Storage Area. 5) Washing, drying and sealing area (wherever required). 6) Sterilization. 7) Testing facilities.
The following equipments and space are recommended for the basic manufacture of different categories of medical devices. -
A. STERILE DISPOSABLE PERFUSION AND BLOOD COLLECTION SETS.
(1) Moulding:
(a) Injection Moulding Machine. (b) Extruder Machine. (c) PVC Resin compounding Machine.
(2) Assembling:
(a) Hand Pressing Machine for filter fixing a Drip Chamber. (b) Bag Sealing Machine. (c) Compressor Machine. (d) Leak Testing Bench (e) PVC Tube Cutting Machine. (f) Tube Winding Machine (wherever necessary). (g) Welding Machine (wherever necessary)
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An area of 30 square meters for Moulding and 15 square meters for Assembling are recommended for basic installation. The assembling area shall be air-conditioned provided with HEPA filters. The moulding section shall, if necessary, have proper exhaust system.
Note: - An additional area of 20 square meters is recommended for any extra category.
B. STERILE DISPOSABLE HYPODERMIC SYRINGES.
(1) Moulding: - (a) Granulator (b) Injection Moulding Machine. (c) Weighing devices.
(2) Assembling:
(a) Blister Pack Machine. (b) Vacuum Dust Cleaner (c) Rubber-tip Washing Machine (d) Foil stamping or screen printing equipment.
An area of 30 square meters for moulding and 15 square metres for assembling are recommended for basic installation. The assembling area shall be air-conditioned provided with HEPA Filters. The moulding section, shall, if necessary, have proper exhaust system.
Note: - An additional area of 20 square meters is recommended for any extra category.
C. STERILE DISPOSABLE HYPRODERMIC NEEDLES.
(1) Moulding:
(a) Needle grinding and leveling machine. (b) Electro Polishing Machine. (c) Cutting Machine
(d) Injection Moulding Machine. (e) Needle Pointing Deburrine Machine (f) Air-compressor.
(2) Assembling:
(a) Needle cleaning Machine with Magnetic Separator. (b) Blister Packing Machine. (c) Needle Inspection Unit.
An area of 30 square meters for Moulding and 15 square meters for Assembling are recommended for basic installation. The assembling area shall be air-conditioned provided with HEPA filters. The molding section shall, if necessary, have proper exhaust system.
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Note: - An additional area of 20 square meters is recommended for any extra category.
3. Raw Materials. - The licensee shall keep an inventory of all raw materials to be used at any stage of manufacture of devices and shall maintain records as per Schedule U. All such raw materials shall be identified and assigned control reference umber. They shall be conspicuously labeled indicating the name of the material, control reference number, name of the manufacturer and be specially labeled “Under Test” or “ Approved” or “Rejected”. The under test, approved or rejected materials shall appropriately be segregated. These shall be tested for compliance with required standards of quality.
A minimum area of 10 Square meters shall be provided for storage of raw materials.
4. Storage Area. - The licensee shall provide separate storage facilities for quarantine and sterilized products.
An area not less than 10 square metre shall be provided for each of them.
5. Washing, drying and sealing area. - The licensee shall provide wherever required adequate equipments like water distillation still, deionizer, washing machine. Dying Oven with trays for washing, drying and sealing of medical device.
An area not less than 10 square metre shall be provided.
6. Sterilization. - The licensee shall provide requisite equipments with required controls and recording device for sterilization of medical devices by Ethylene Oxide Gas in his own premises or may make arrangements with some Institution approved by the Licensing authority for sterilization. The products sterilized in this manner shall be monitored to assure acceptable levels of residual gas and its degradation products. An area of 10 square meters is recommended for basic installation of such facility.
Provided that the above equipment may not be required in case the licensee opts for sterilization of medical devices by Ionising Radiation.
7. Testing Facilities. - The licensee shall provide testing laboratory for carrying out Chemical and Physio-Chemical testing of medical devices and of raw materials used in its own premises:
Provided that the Licensing Authority shall permit the licensee in the initial stage to carry out testing of Sterility, Pyrogens, Toxicity on their products from the approved testing institutions but after one renewal period of licensee shall provide testing facilities of all such tests in their own premises.
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8. Records. - The licensee shall maintain records of different manufacturing activities with regard to each stage of manufacture in-process control, assembling, packing, batch records for the quantity of devices manufactured from each lot of blended granules, duration of work, hourly quantum of production in respect of each item as well as record of each sterilizing cycle of the gaseous method employed.
Note: - The above requirements of machinery, equipments, space, qualifications are made subject to the modification at the discretion of the Licensing Authority, if he is of the opinion that having regard to the nature and extent of the manufacturing operations it is necessary to relax or alter them in the circumstances of a particular case.]
? [SCHEDULE N [See Rule 64(1)]
List of minimum equipment for the efficient runninig of a pharmacy:-
I. Entrance. - The front of a pharmacy shall bear an inscription “Pharmacy” in front.
II. Premises. - The premises of a pharmacy shall be separated from rooms for private use. The premises shall be well built, dry, well lit and ventilated and of sufficient dimensions to allow the goods in stock especially medicaments and poisons to be kept in a clearly visible and appropriate manner. The area of the section to be used as dispensing department shall be not less than 6 square meters for one pharmacist working therein with additional 2 square meters for each additional pharmacist. The height of the premises shall be at least 2.5 meters.
The floor of the pharmacy shall be smooth and washable. The walls shall be plastered or tiled or oil painted so as to maintain smooth, durable and washable surface devoid of holes, cracks and crevices.
A pharmacy shall be provided with ample supply of good quality water.
The dispensing department shall be separated by a barrier to prevent the admission of the public.
_______________________________________________________________________ ? Subs by G.O.I. Notification No.S.O.2139 dt12.08.1972.
540
III. Furniture and apparatus. - The furniture and apparatus of a pharmacy shall be adapted to the uses for which they are intended and correspond to the size and requirements of the establishment.
Drugs, chemicals, and medicaments shall be kept in a room appropriate to their properties and in such special containers as will prevent any deterioration of the contents or of contents of containers kept near them. Drawers, glasses and other containers used for keeping medicaments shall be of suitable size and capable of being closed tightly to prevent the entry of dust.
Every container shall bear a label of appropriate size, easily readable with names of medicaments as given in the Pharmacopoeias.
A pharmacy shall be provided with a dispensing bench, the top of which shall be covered with washable and impervious material like stainless steel, laminated or plastic, etc.
A pharmacy shall be provided with a cupboard with lock and key for the storage of poisons and shall be clearly marked with the work ‘poison’ in red letters on a white background.
Containers of all concentrated solution shall bear special label or marked with the works “To be diluted”.
A Pharmacy shall be provided with the following minimum apparatus and books necessary for making of official preparations and prescriptions:-
Apparatus: - Balance, dispensing, sensitivity 30 mg. Balance, counter, capacity 3 Kgm., sensitivity 1 gm. Beakers, lipped, assorted sizes Bottles, prescription, ungraduated assorted sizes Corks assorted sizes and tapers. Cork, extracter Evaporating dishes, porcelain. Filter paper Funnels, glass Litmas paper, blue and red Measure glasses cylindrical 10 ml, 25 ml, 100 ml and 500 ml Mortars and pestles, glass Mortars and pestles, wedgwood. Ointment pots with bakelite or suitable caps. Ointment slab, porcelain Pipettes, graduated, 2 ml, 5 ml and 10 ml
541
Ring, stand (retort) iron, complete with rings. Rubber stamps and pad Scissors Spatulas, rubber or vulcanite Spatulas, stainless steel. Spirit lamp Glass stirring rods Thermometer, 0oC to 200oC Tripod stand Watch glasses Water bath Water distillation still in case Eye drops and Eye lotions are prepared. Weights, Metric, 1 mg. to 100 gm Wire Gauze *Pill finisher, boxwood * Pill Machine * Pill Boxes * Suppository mould
Books : The Indian Pharmacopoeia (current Edition) National Formulary of Indian (Current Edition) The drugs and Cosmetics Act, 1940 The Drugs and Cosmetics Rules, 1945 The Pharmacy Act, 1948 The Dangerous Drugs Act, 1930
4. General provisions. - A pharmacy shall be conducted under the continuous personal supervision of a Registered Pharmacist whose name shall be displayed conspicuously in the premises.
The Pharmacist shall always put on clean white overalls.
The premises and fittings of the pharmacy shall be properly kept and everything shall be in good order and clean.
All records and registers shall be maintained in accordance with the laws in force.
Any container taken from the poison cupboard shall be replaced therein immediately after use and the cupboard locked. The keys of the poison cupboard shall be kept in the personal custody of the responsible person.
Medicaments when supplied shall have labels conforming to the provisions of laws in force.
542
Note: - The above requirements are subject to modifications at the discretion of the licensing authority, if he is of opinion that having regard to the nature of drugs dispensed, compounded or prepared by the licensee. It is necessary to relax the above requirements or to impose additional requirements in the circumstances of a particular case. The decision of the licensing authority in that regard shall be final.
* These items are to be provided only by those who intend to dispense pills or suppositories, as the case may be.]
1[SCHEDULE O
[See Rule 126]
STANDARD FOR DISINFECTANT FLUIDS PART 1
Provision applicable to Black fluids and White Fluids.
1. Classification. - The disinfectants shall be classified as follows: - (A) Black fluids (B)White fluids
(A) Black fluids. – These shall be homogeneous dark brown solution of coal tar acid or similar acids derived
from petroleum with or without hydrocarbon, and/or other phenolic compounds, and their derivatives and a suitable emulsifier.
(B) White fluids. – These shall be finely dispersed homogeneous white to off-white emulsion consisting of
coal tar acids or similar acids derived from petroleum, with or without hydrocarbons, and/or other phenolic compounds, and their derivatives.
2. Gradation - Each of the above classes of disinfectant fluids shall be graded on the basis of the minimum requirements in respect of:
Rideal Walker (RW) Coefficient as follows: -
Grade Rideal Walker (RW) Coefficient (Minimum)
1. 18
2. 10
3. 5
___________________________________________________________________________ 1Subs.by G.O.I.Notification No. G.S.R.1243(E) dt.19.09.1979.
543
3. Type. - Each of the above grades of disinfectant fluids shall be stable in the range of temperature indicated against each type. -
Type Stable in the range of (I) Normal 15oC to 45oC. (II) Winter 5 oC to 30 oC
4. Requirements. - All classes and grades of disinfectant fluids shall comply with the following requirements, namely: -
(1) Stability after dilution. - When tested by the method described hereinafter the disinfectant fluids shall be miscible with artificial hard water (for Black fluids) or with artificial sea water (for White fluids) in all proportion from 1 per cent to 5 per cent by volume, to give emulsion which shall not break or show more than traces of separation of either top or bottom oil when kept for 6 hours at 15o to 45oC for Type (I) (Normal) and 5oC to 30oC for Type (II) (Winter).
(2) Germicidal Value. - Rideal Walker Coefficient – Black fluids and White fluids shall be used tested for determination of Rideal Walker Coefficient (R.W.Coefficient) by the method described hereinafter.
(3) Storage. - Disinfectant fluids of all classes shall be stored in mild steel, tinned mild steel or other suitable containers. These shall not be stored in containers made of galvanized iron.
(4) Labelling. -Subject to the other provisions in these rules, the label on the container shall state-
(j) the name of the product
(ii) the name and full address of the manufacturer,
(iii) grade, type, R.W. Coefficient of product,
(iv) date of manufacture,
(v) quantity present in the container,
(vi) indications and mode of use, and
(vii) date up to which the product can be used
5. Method of testing - (1) Preparation of sample. - The sample of disinfectant fluids to be tested should be
mixed thoroughly taking care that no air is beaten into the fluid immediately before withdrawing any portion for testing. The rest portion should be withdrawn from the middle of the sample.
544
(2)Method of resting stability after dilution. - (a) Preparation of Artificial Hard Water: 40ml of I N Hydrochloric Acid (Analytical
Reagent Quality) is neutralized with a slight excess of Calcium Carbonate and filtered. The filtrate is diluted to 1000 ml with distilled water, 10 parts of this solution is further diluted to 100 parts with distilled water.
(b) Preparation of Artificial Sea Water: 27G of Sodium Chloride (Analytical Reagent Quality) and 5 G of Magnesium Sulphate (Analytical Reagent Quality) are dissolved in distilled water and diluted to 1000 ml. the solution is filtered before use.
(c) Procedure: Take 1 ml and 5 ml portions of the sample in duplicate in 100 ml stoppered measuring cylinder (IS: 878 – 1956) by means of pipettes. Dilute the sample with artificial Hard water or Artificial Sea water (as the case may be) upto 10 ml mark. Mix thoroughly by inverting the cylinders 5 times. Keep the cylinders containing the diluted fluids for 6 hours at the extremes of the temperature range specified for the particular type. The sample complies with the test if the solution shows not more than a trace of separation at its top and bottom.
(3) Method of determination of Rideal Walker Coefficient (R.W.C)
(a) Apparatus – A loop, 4 mm in internal diameter is made at the end of 28 swg (0.376 mm) wire of platinum or platinum iridium alloy, 38mm long from the loop to the holder. The loop is bent at such an angle to the length of the wire and will facilitate in removal vertically from the surface of the liquid while keeping the place of the loop horizontal.
Incubator – Set and maintained at 37oC ± 1oC
Pipettes – Standard graduated pipettes of capacity 10 ml; 5 ml and 1 ml
Dropping Pipette – Made of delivery 0.2 ml
Medication tubes – 5 sterile plugged rimless test tubes 125 mm x 22 mm (5” x ¾“) made of hard neutral glass.
Both tubes – About 2 dozens of the same description as medication tubes.
Standard measuring cylinders stopped and graduated- 500ml graduated in 10 ml-; 100ml graduated 1 ml- five. All apparatus must be scrupulously clean and sterile immediately before use.
Regents- (a) Broth- Prepare a mixture of the following ingredients:
545
Meat extract (Microbiological grade) 20 g Peptone (Micro biological grade) 20 g Sodium Chloride (Regent Quality) 10 g Distilled Water- 1000 ml.
Dissolve the solids in distilled water, add sufficient sodium hydroxide to neutralize the solution; then boil it to bring down phosphates and filter while hot. The broth thus prepared is then adjusted to pH 7.6 with normal Hydrochloric acid. The broth is then sterilized b autoclaving at 15 lbs pressure for 20 minutes. It is then filtered and placed in 5 ml quantities in sterilized broth tubes. The tubes of media thus prepared are sterilized by autoclaving at 15 lbs pressure for 10 minutes. The final pH of the medium should lie between 7.3 and 7.5. Further sterilization in bulk or in tubes is not possible.
(b) Test Organism- Test organism used is Salmonella typhi (NCTC 786) of which suitable culture shall be obtained from the Director, Central Drugs Laboratory, Calcutta. This culture is maintained by weekly subculture on a nutrient agar slope (made by dissolving 2.5 per cent Agar Agar (Bacteriological grade) in broth prepared as above), incubating the subculture for 24 hours at 37OC and then storing in refrigerator at a temperature below 22oC. For the purpose of the test a little the growth from the most recent subculture in nutrient agar slope is placed in tube of R.W. broth and incubated for 23 hours at 38oC. A standard loopful is then transferred to a second tube and incubated as before. This is done at least three times before a test is carried out. Sub-cutting in broth is limited to 14 days.
(c) Standard phenol: 5 per cent W/V solution in sterile distilled water of chemically pure phenol having a crystallizing point of not less than 40.5oC is prepared. Test dilutions are prepared from this stock solution containing 1 g of phenol in each 95, 100, 105, 115 ml of the solution made. These dilutions shall be used within a week of preparation.
(d) Test dilutions of Disinfectant (sample)- The sample is prepared as described under “Preparation of samples”. A test portion of 5 ml is withdrawn and discharged into about 480 ml of sterile distilled water in a 500ml glass stoppered sterile measuring cylinder and the pipette is rinsed three times or more in the clear liquid. The whole is then made up to 500ml with sterile distilled water, the cylinder is stoppered and the contents thoroughly mixed by inverting the cylinder several time. Suitable test dilutions in sterile distilled water are then immediately prepared from this stock solution.
Procedure: 5 ml of 4 chosen dilutions of the disinfectant are placed in 4 medication tubes which are than placed in a rack provided with water bath maintained at a constant temperature between 17oC and 19 oC, with the strongest dilution on the left. The fifth medication tube containing 5 ml of the particular phenol dilution is placed on the right. When the content on the medication tubes and broth culture of the test organism have reached the temperature of the water bath, starting at Zero time, 0.2 ml of the culture is added to the left hand medication tube and the tube is shaken gently. After 30 seconds the next tube is inoculated similarly and the process is repeated with each successive tube at intervals of 30 seconds until the phenol control has been inoculated. Thirty seconds after this last addition (that is 2-1/2 minutes from
546
zero) a loopful of the well-shaken content of the tube at the extreme left is withdrawn and placed in tube containing 5 ml of the broth medium. Thirty seconds after this similar operation is performed on the second medication tube. The procedure is repeated at an interval of 30 seconds with each of the 5 medication tubes working from left to right until 4 sets of cultures have been made i.e. at 2-1/2, 5, 7-1/2 and 10 minutes respectively after exposure. In each withdrawal care should be taken to ensure that the loop is removed vertically from the surface of the liquid with its plane horizontally and without touching the side of the test tubes. The loop shall be sterilized by flaming between each operation, care being taken that the loop is cooled before being again used. The inoculated broth tubes are incubated for not less than 48 hours and not more than 72 hours at 37oC when the tubes showing growth of the test organisms will be recognized by turbidity of the broth.
Calculation of Coefficient- The R.W. Coefficient is obtained by dividing that dilution of the disinfectant which shows life of test organism in 2-1/2 and 5 minutes but no life thereafter by that dilution of the phenol which gives the same response.
A typical set of sample is given below:
Sample disinfectant Time of exposures in minutes Dilutions. _____________________________
2½ 5 7½ 10 ____________________________________________________________________
1: 1000 - - - - R.W.Coefficient 1200 = 12 100
1: 1100 + - - -
1: 1200 + + - -
1: 1300 + + + -
Phenol control
1: 100 + + - - __________________________________________________________________________
(+ = growth - = No growth)
PART II
Provisions applicable to other disinfectant fluids:
Disinfectant fluids which are made with chemicals other than those specified under Part I of this Schedule shall conform to the formula or list of ingredients shown on the label.
547
Labelling : Subject to the provisions of rules on labeling, the label of container shall state-
(i) the name of product
(ii) the name and full address of the manufacturer;
(iii) the full formula or list of ingredients of the preparation;
(iv) date of manufacture;
(v) date up to which the product can be used;
(vi) quantity present in the container, and
(vii) indications and mode of use.
Cautionary note:
Mercury compounds shall be strictly excluded from all grades.]
548
*[SCHEDULE P [See Rule 96]
LIFE PERIOD OF DRUGS
Sl. No.
Name of the drug Period in months (unless otherwise specified) between date of manufacture and date of expiry which the labeled potency period of the drug shall not exceed under the conditions of storage specified in Column No.4.
Condition of storage
1 2 3 4 ANTIBIOTICS 1. Adramycin 30 In a cool place 2. Ampicillin 36 In a cool place 3. Ampicillin Capsules 24 4. Ampicillin Dry Syrup 24 5. Ampicillin Injection 24 6. Ampicillin Sodium 36 In a cool place 7. Ampicillin Trihydrate 30 In a cool place 8. Amoxycillin rihydrate 36 In a cool place 9 Amoxycillin Trihydrate Capsules 24 10. Amoxycillin Trihydrate Dry Syrup 18 11. Bacitracin 18 In a cool place 12. Bacitracin or Zinc Bacitracin Tablets 12 13. Bacitracin Lozenges 12 14. Carbenicillin Sodium Injection 24 At temperature not
exceeding 5oC.
15. Carbenicillin Sodium Powder 24 At temperature not exceeding 5oC.
16. Cephalexin 24 In a cool place 17. Chloramphenicol 60 In a cool place 18. Chloramphenicol Capsules & Tablets 48 19. Chloramphenicol Palmitate 48 __________________________________________________________________________ * Subs. by G.O.I. Notification No. GSR 17(E) dt 7.1.1986 w.e.f. 7.1.1986
549
1 2 3 4 20. Chloramphenicol Palmitate Oral Suspension 36 21. Chloramphenicol Eye drops 24 22. Chloramphenicol Sodium Succinate Powder 48 In a cool palace 23. Chloramphenicol Sodium Succinate Injection 36 In a cool place 24 Chlortetracycline Hydrochloride 60 In a cool place 25. Chlortetracycline Hydrochloride Capsules 60 26. Chlortetracycline Hydrochloride Tablets 24 27. Chlortetracycline Hydrochloride Ointment 24 28. Cloxacillin (Oral) 36 In a cool place 29. Cloxacillin Sodium (Injection Grade) 36 In a cool place 30. Colistin Sulphate 60 Protected from light 31. D-Cycloserine 48 In a cool place 32. Dimethyl chlortetracycline Hydrochloride 48 33. Dimethyl Chlortetracycline Hydrochloride
Capsules. 36
34. Daunoblastin Injection. 36 35. Doxycycline Hydrochloride 48 In a cool place 36. Doxcycline Monohydrate 36 In a cool place 37. Doxycyline Monohydrate for Oral Suspension. 24 38. Doxycycline Monohydrate Capsules. 36 39. Erythromycin Estolate 36 In a cool place 40. Erythromycin Ethylsuccinate 60 In a cool place 41. Erythromycin Oral Suspension 36 42. Erythromycin Estolate for Oral Suspension 36 43. Erythromycin Ethyl Succinate Tablet. 24 44. Erythromycin Estolate Tablets 24 45. Erythromycin Stearate 36 In a cool place 46. Framycetin Sulphate 48 In a well closed contained
with temperature not exceeding 30oC
47. Framycetin Sulphate Eye drops 24 In a well closed container with temperature not exceeding 30oC
48. Framycetin Sulphate Ointment. 24 In a well closed container with temperature not exceeding 30oC.
49. Gentamycin Sulphate 60 In a cool place. 50. Gentamycin Sulphate Injection 36 51. Gramicidin 60 In a cool place 52. Griseofulvin 48 In a cool place
550
1 2 3 4
53. Griseofulvin Tablets 36 54. Kanamycin Sulphate Injection. 24 55. Kanamycin Acid Sulphate Powder 48 In a cool place 56. Mitomycin C 48 In a cool place 57. Neomycin Sulphate. 48 In a cool place 58. Nystatin 36 At temperature not exceeding 5oC. 59. Oleandomycin Phosphate sterile 24 In a cool place 60. Oleandomycin Phosphate non sterile 36 In a cool place 61. Oxytetracline Hydrochloride 36 In a cool place 62. Oxytetracycline Hydrochloride Capsules. 36 63. Oxytetracycline Hydrochloride Tablets 24 64. Oxytetracycline Hydrochloride Injection 24 65. Oxytetracycline Hydrochloride Ointment 36 66. Penicillin Crystalline 36 In a cool place 67. Penicillin Tablets 18 In a cool place 68. Procaine Penicillin G 36 In a cool place 69. Benzathin Penicillin G 48 In a cool place 70. Potassium Phenoxy Methyl Penicillin 48 In a cool place 71. Potassium Phenoxy Methyl PenicillinTablets 24 72. Polymixin B Sulphate 48 In a cool place 73. Polymixin B Sulphate Ointment or Powder 24 In a cool place 74. Rifampicin 36 In a cool place 75. Rifampicin Capsules *[36] 76. Spramycin Base 24 In a cool place 77. Strepromycin Injection. 36 78. Streptomycin Ointment 24 79. Streptomycin Tablets 24 80. Streptomycin Sulphate 48 At temperature not exceeding 20oC 81. Tetracycline Base 24 In a cool place 82. Tetracycline Hydrochloride 36 In a cool place 83. Tetracycline Hydrochloride Capsules 36 84. Tetracycline Tablets 24 85. Tyrothricin 60 In a cool place.
VITAMINS. 1. Vitamin A Injection 24 2. Vitamin BI Injection 24 3. Thiamine Mononitrate Tablets 36
551
1 2 3 4 4. Thiamine Hydrochloride 48 In a well closed container, protected from
light, in a cool place. 5. Thiamine Mononitrate 48 In a well closed container, protected from
light, in a cool place. 6. Riboflavin 60 In a well closed container, protected from
light, in a cool place. 7. Riboflavin 5 Phosphate 24 In a well closed container, protected from
light, in a cool place. 8. Riboflavin Tablets 36 9. Vitamin B2 Injection 24
10. Vitamin B6 60 In a well closed container, protected from light, in a cool place.
11. Vitamin B6 tablets 36 12. Cyanacobalamin 48 In a well closed container, protected from
light, in a cool place. 13. Hydroxycobalamin 48 In a well closed container, protected from
light, in a cool place. 14. Vitamin B12 Injection 36 15. Calcium Pantothenate 36 In a well closed container, protected from
light, in a cool place. 16. Vitamin C Injection 24 17. Calcium Pantothenate Tablets 36 18. Vitamin C 48 In a well closed container, protected from
light, in a cool place. 19. Vitamin D2 D3 36 In a well closed container, protected from
light, in a cool place. 20. Vitamin E or E-Acetate 60 In a well closed container, protected from
light, in a cool place. 21. Folic Acid 60 In a well closed container, protected from
light, in a cool place. 22. Folic Acid Tablets 36 23. Vitamin K 60 In a well closed container, protected from
light, in a cool place. 24. Vitamin K Injection 36 25. Niacinamide 60 In a well closed container, protected from
light, in a cool place. 26. Niacinamide Tablets 36 27. D-Panthenol 60 In a well closed container, protected from
light, in a cool place.
1 2 3 4
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INSULIN PREPARATIONS 1. Globuline Zinc Insulin Injection 24 At temperature between 2oC and 8oC,
must not be allowed to freeze. 2. Insulin Injection 24 At temperature between 2oC and 8oC,
must not be allowed to freeze. 3. Insulin Zinc Suspension 24 At temperature between 2oC and 8oC,
must not be allowed to freeze. 4. Isophane Insulin Injection. 24 At temperature between 2oC and 8oC,
must not be allowed to freeze. *[5. Human Insulin Injection 30 At temperature between 2oC and 8oC,
must not be allowed to freeze. NORMAL HUMAN PLASMA 1. Anti-Haemophillic Human Globulin 12 In a cool place 2. Dried Plasma 60 At temperature between 2oC and 8oC,
must not be allowed to freeze. 3. Dried Normal Human Serum Albumin 60 At a temperature not exceeding 25oC
4. Frozen Plasma 24 In deep freeze 5. Liquid Plasma 24 In cold place 6. Liquid Normal Human Serum Albumin. 60 In cold place.
**[7 Whole Human Blood- (a) Collected in ACD solution (b) Collection in CPDA solution.
21days 35days
At temperature between 4oC and 6oC At temperature between 4oC and 6oC]
SERA TOXIN AND TOXOID
1. Alum Precipitated Diphtheria Toxoid 24 In cold place. 2. Alum Precipitated Diphtheria and
Tetanus toxoid and Pertusis vaccine combined
18 In cold place
3. Alum Precipitated Tetanus Toxoid 24 In a cold place 4. Aluminium Hydroxide
Absorbed Diphtheria Toxoid 24 In a cold place.
5. Aluminium hydroxide Absorbed Diphtheria Tetanus Toxoid and Pertussis Vaccine combined.
18 In a cold place
*Ins. by G.O.I. Notification No. GSR 215(E) dt 19.3.1999. ** Sub. by G.O.I. Notification No. GSR 626(E) dt 14.10.1991.
553
1 2 3 4
6. Aluminium Phosphate Absorbed Diphtheria Toxoid.
24 In a cold place.
7. Aluminium Phosphate absorbed Diphtheria and Tetnus Toxoid
24 In a cold place.
8. Aluminium phosphate absorbed diphtheria Toxoid Tetanus Toxoid and Pertussis vaccine combined.
18 In cold place
9. Diagnostic Diphtheira Toxin (Schick Test) 12 In cold place 10. Cobra venom in solution 3 Between 2oC and 5oC protected from
light. 11. Diphtheria Toxoid 24 In cold place 12. Inactivted Diagnostic Diphtheria Toxin. 12 In cold place 13. Liquid serum 12 Between 2oC and 10oC preferable at
the lower limit. 14. Lyophilised anti-snake venom serum 60 15. Lyophilised Schick test Toxin and control 60 16 .Old Tuberculin 60 In cold place 17. Thrombin (Bovine origin) 36 In cold place. 18. Tetanus Toxoid 24 In cold place 19. Tuberculin PPD 60 In cold place
OTHER VACCINES.
1. Alum precipitatd pertussis Vaccine. 18 In cold place 2. BCG Vaccine 14 days In cold place 3. Cholera Vaccine 18 In cold place 4. DHL Vaccine (for dog) 12 In cold place 5. Measles Vaccine 24 In cold place 6. Plague Vaccine 36 In cold place 7. Polio Vaccine 24
6 3
When stored at minus 20oC When stored at Zero oC When stored at 4 oC
8. Rabies vaccine 6 In cold place 9. Typhoid vaccine 18 In cold place 10. Typhoid and Para Typhoid Vaccine. 18 In cold place 11. Typhoid Para Typhoid A and B vaccine. 18 In cold place 12. Typhoid Para Typhoid A,B & C Vaccine 18 In cold place 13. Typhoid Para Typhoid A, B & C and
Tetanus Vaccine. 18 In cold place
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1 2 3 4 14. Typhus vaccine 12 In cold place 15. Yellow Fever Vaccine 12 In cold place * [16 Anti-Rabies Vaccine (Cell Culture) 24 In cold place.]
ANTITOXIN
(For serum extracted preparations) 20% Excess potency 12 In cold place 30% Excess potency 24 In cold place 40% Excess potency 36 In cold place 50% Excess potency (for enzyme preparations)
48 In cold place
5% Excess potency 12 In cold place 10% Excess potency 24 In cold place
15% Excess potency 36 In cold place
20% Excess Potency 48 In cold place
MISCELLANEOUS DRUGS
1. Andrenaline for Injection. 12 In cold place. 2. Chorionic Gonadotrophin for
Injection (Lyophilised) 36 At temperature not exceeding 20oC.
3. Corticotrophin 24 In cold place 4. Corticotrophin Lyophilised 36 In cold place 5. Heparin Injection 36 In a cool place. 6. Liquid Extract of Ergot 12 In cold place 7. Liver Extract Crude Injection. 24 In a cool place 8. Oxytocin Injection 24 In cold place 9. Paraldehyde Injection 6 In cool place protected from light. 10. Pituitary Injection 24 In cold place. 11. Vasopressin Injection. 24 In cold place.
Note : (1) The term “cool place” means ‘place having a temperature between 10oC and 25oC. (2) The term “cold place” means a place having a temperature not exceeding 8 oC. (3) Capsules should be kept in a well-closed container at temperature not exceeding 30 oC. (4) Wherever condition of storage is not specified in Column 4, it may be stored under
normal room temperature.] __________________________________________________________________________ *Ins. by G.O.I. Notification No. GSR 215(E) dt 19.3.1999.
555
*[SCHEDULE P-1 [See Rule 105]
PACK SIZES OF DRUGS
Name of the Drug Dosage form Pack size 1 2 3
Albendazole Suspension 10ml
Atenolol Tablets 14
Anti-Haemmorhoidal Topicals Rectal Capsules 20
Aspirin (Low-dose) Tablets 14
Cholecalciferol or Ergocalciferol Granules 1 gm. Sachet
Ciclopiroxolamine Vaginal Cream 30 gms.
Catalin Ophthalmic drops 15 ml
Famotidine Tablets 14
Glyceryl Trinitrate Spansules (Long Acting) 25
Isosorbide Dinitrate Spansules (Long Action) 25
Isoniazide Syrup 200 ml
Ipecacuanha Syrup 10 ml
Oral Rehydration Salt (ORS) Powder Pouches to be reconstituted to one litre in one pack or in 5 unit does sachets in one pack.
Piperazine Granules 5 gm.
Syrup 30 ml
Pyrantel Pamoate Syrup 8 ml or 10 ml
Potassium Chloride. Syrup 60 ml and 200 ml.
Progestogen Qestrogen (Combinations for Oral
Contraception)
Tablets 21 or 22 with or without 7 placebo.
______________________________________________________________________________ * Ins. by G.O.I. Notification No. GSR 796(E) dt 1.10.1992
556
Name of the Drug Dosage form Pack size 1 2 3
Roxatidine Acetate Hydrochloride Tablets 14
Vitamin A Oral Drops Drops 7.5 ml] 1[Co-trimoxazole Suspension 50 ml
Haloperidol Oral Solution 15 ml
Loxapine Oral Liquid Concentrate 15 ml ]
2SCHEDULE Q
[ See rules134 and 144] 3[Part I]
4[List of Dyes, colours and Pigments permitted to be used in Cosmetics and Soaps as given under IS : 4707 (Part I)-1988 as amended by the Bureau of Indian Standards].]
Common name of the colour
Colour Index Number
Chemical name of the colour
1 2 3
Guinea Green B 42085 Monosodium salt of 4-(N-ethyl-p-sulfobenzylamino) – diphenylmethylone-(1-(N-ethyl-N-p-sulfoniumbenzyn( � 2,5-cyclohexadienimine).
Light Green SF Yellowish
42095 Disodium salt of 4-[4 (N-ethyl-p-sulfo benzylamine)- phenyl)-4-sulphoniumphenyl) methylene]-(2 (N-ethyl-N- sulfobenzyl) ? 2,5-Cyclohexadienimine.
Tartrazine. 19140 Trisodium salt of 3-carboxy-5-hydroxy-1-p-sulfophenyl-4- p-sulfophenylazo-pyrazole.
Sunset yellow FCF. 15985 Disodium salt of 1-p-sulfophenylazo-2- naphthol-6- sulfonic acid.
Ponceau 3R 16155 Disodium salts of a mixture of 1-alkyl- phenylazo-2- napthol 3, 6-disulfonic acids.
______________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 753(E) dt 4.11.1999 2Ins. by G.O.I. Notification No. GSR 1183 dt 17.8.1964. 3Renumbered as Part I by G.O.I. Notification No. GSR 11(E) dt 7.1.1991. 4Subs. by G.O.I. Notification No. GSR 811(E) dt 14.11.1994.
1 2 3
557
Amarnath. 16185 Trisodium salt of 1-(4-sulfo-1- napthylazo) 2-naphthol 3, 6- disulfonic acid.
Erythrosine. 45430 Disodium salt of 9-0-carboxyphenyl-6- hydroxy 2,4,5, 7- tetraiodo-3- isoxanthone.
Ponceau SX. 14700 Disodium salt of 2-(5 sulfo-2, 4-xylyl- azo)-1-naphthol-4- sulfonic acid.
Brilliant Blue FCF 42090 Disodium salt of 4-(9-4-(N-ethyl-p-sulfobenzylamino)- phenyl)-2-sulfonium phenyl)- methylene)-(1-(N-ethtl-N-p- sulfobenzyl)- ? 2, 5-cyclohexadienimine).
Indigocarmine. 73015 Disodium salt of 5,5’-indigotindisulfonic acid.
Wool Violet 5 BN (Acid violet 6B)
42640 Monosodium salt of 4-(N-ethyl-p-sulfobenzylamino)- phenyl)-(4-(N-ethyl-p-(sulfonium-benzylamine)-phenyl) methylene)-(N, N-dimethyl-? 2,5-cyclohexadienimine)
Light Green SF Yellowish 42095
Calcium salt of 4-(4-(N-ethyl-p-sulfobenzylamino)-phenyl) (4-sulfonium-phenyl)methylene), (1-(N-ethyl-N-p- sulfobenzyl)- ? 2,5-cyclohexadienimine).
Alizarin Cyanine Green F 61570 Disodium salt of 1,4-bis (O-sulfo-p-toluino)anthraquinone)
Quinazarine Green SS. 61565 1,4-bis-(p-Toluino)-anthraquinone Fast Green FCF. 42053 Disodium salt of 4-(4-(-ethyl-p-sulfobenzylamino)-phenyl)
(4-hydroxy-2 sulphoniumphenyl) methylene)-(1-N-ethyl- N-p-sulfobenzyl) ? 2,5, cyclohexadienimine).
Acid Fast Green 42100 Monosodium salt of 4-(4-N-ethyl-p-sulfobenzylomino) phenyl)-(o-chlorophenyl)-methylene)- 1-(N-ethyl-N- p- sulfonium-benzyl- ? 2,5, cyclohexadienimine).
Pyranine Concentrated. 59040 Trisodium salt of 10-hydroxy-,3,5,8-pyrene-trisulfonic acid.
Quinoline Yellow WS. 47005 Disodium salt of disulfonic acid of 2-(2-Quinolyl)-1, 3- indandione.
Quinoline Yellow SS 47000 2-(2-quinolyl)-1, 3 indandiene. Poneceau 2 R. 16150 Disodium salt of 1 xylylazo-2-naphthol-3, 6-disulfonic
acid. Lithol Rubin B. 15850 Monosodium salt of 4-(o-sulfo-p-tolylazo)3 hydroxy-2-
naphthoic acid. Lithol Rubin BCA 15850 Calcium salt of 4-(o-sulfo-p-tolylazo)-3-hydroxy-2-
naphthoic acid
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1 2 3
Lake Red D. 15500 Monosodium salt of 1-0-carboxyphenylazo-2- naphthol.
Lake Red DBA 15500 Barium salt of 1-o-carboxyphenylazo-2-naphthol.
Lake Road DCA. 15500 Calcium salt of 1-o-carboxyphenylazo-2-naphthol.
Toney Red. 26100 I-p-phenylazophenylazo-2-naphthol. Oil Red OS. 26125 I-Xylylazoxylylazo-2-napththol .Tetrabromofluorescein 45380 2,4,5,7-Tetrabromo-3, 6-flurandiol. Eosin TS 45380 Disodium salt of 2,4,5,7-tetrabromo-9-0
carboxyphenyl-6-hyroxy-3-isoxanthone. Eosin YSK. . 45380 Dipotassium salt of 2,4,5,7-tetrabromo-9-0
carboxyphenyl-6-hyroxy-3-isoxanthone Tetrachlorofluorescein NA 45366 2,4,5,7- tetrachloro-S, 6-Fluorandiol
Tetrachlorofluorescein K. 45366 Disodium salt of 9-0-carboxyphenyl-2,4,5,7- tetrachloro-6-hydroxy-3-isoxanthose.
Tetrachloro Tetrabromo floure scein
45410 2,4,5,7-Tetrabromo-12,13,14,15-tetrachloro-3,6fluora- ndiol.
Phloxine B 45410 Disodium salt of 2,4,5,7-tetrabromo-9(3,4,5,6-tetra chloro-o-carboxyphenyl)-6-hydroxy-3-isoxanthone
Bluish Orange T.R. 45457 1,4,5,8, 15-Pentabromo-2, 7-dicarboxy-3, 6-fluoran diol.
Helindone Pink CN. 73360 5, 5-Dichloro-3, 3’ dimethyl-thio indigo Brilliant Lake Red R 15800 Calcium salt of 3-hydroxy-4-phenylazo-2-naphthoic
acid. Deep Maroon (Fanchon Maroon)
15880 Calcium salt of 4-(I-sulfo-2-naphthylzo (3- hydroxy-2- naphtoic acid.
Toluidine Red.. 12120 1-(o-Nitro-p-tolylazo)-2-naphthol.
Flaming Red. 12085 I- (o-Chloro-p-nitrophenylazo)-2-naphthol
Deep Red (Maroon). 12350 3-Hydroxy-N- (m-nitrophenyl)-4-(o-nitro-p-tolylazo)- 2-naphthamide.
Alba Red. 13058 o-(p,B,B-Dihydroxy-diethylamino)- phenylazo)- benzoic acid.
Orange G. 16230 Disodium salt of 1-phenylazo-2-naphthol-6-8- disulfonic acid.
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1 2 3
Orange II 15510 Monosodium salt of 1-p-sulfophenylaxo-2-naphthol. Dichlorofluorescein 45365 4,5-Dichloro-3, 6-fluorandiol. Dichlorofluorescein. NA 45365 Disodium salt of 9-o-carboxyphenyl-4,5- dichloro-6-
hydroxy-3-isoxanthone Diiodofluorescein. 45425 4,5 –Diiodo-3, 6-fluorandiol Erythrosine Yellowish NA. 45425 Disodium salt of 9-o-carboxyphenyl-6- hydroxy-4, 5-
diiodo-3-isoxanthone. Erythrosine Yellowish K. 45425 Dipotassium salt of 9-o-carboxyphenyl-6-hydroxy-4,
5-diiodo-3-isoxanthone. Erythrosine Yellowish NH 45425 Dipotassium salt of 9-o-carboxyphenyl-6-hydroxy-4,
5-diiodo-3-isoxanthone Orange TR 45456 4,5, 15-Tribromo 2, 7-dicarboxy-3, 6- fluorandiol. Alizarin. 58000 1,2- Anthraquinonediol. Dibromodiiodofluorescein. 45371 4 ,5- Dibromo-2, 7-diiodo-3, 6-fluorandiol.
Resorcin Brown. 20170 Monosodium salt of 4-p-sulfophenylazo-2(2) 4, xylylazo)-1, 3-resorcinol.
Alphazurine FG. 42090 Diammonium salt of 4-(N-ethyl-p- sulfobenzyl) amine-phenyl) 2-sulfoniumphenyl. Methytlene (-1 (N ethyl-N-p-sulfobenzyl ? (2 ,5-cyclohexandienimine).
Allarin Astro B. 1530 Monosodium salt of 1-methylamino-4-(o-sulfo-p- toluino)-anthroquinone.
Indigo. 73000 Indigotin. Patent Blue NA. . 42052 Monosodium salt of 4-(4- (N-ethyl- benzylamino)-
phenyl –5 hydroxy-4-sulfo-2-sulfoniumphenyl, methylene)- (N-ethyl-Benzyl- ? 2 5-cyclohexadie- nimine).
Patent Blue CA. 42052 Calcium salt of 4-(4- (N-ethyl- benzylamino)-phenyl – 5 hydroxy-4-sulfo-2-sulfoniumphenyl, methylene)- (N- ethyl-N-benzyl- ? 2, 5-cyclohexadienimine).
Curbrantherene Blue 69825 3- 3- Dichlorolindanthrene. Nibhihol Blue Black 20470 Disodium salt of 8-amino-7-p- nitrophenylazo 3-
phenylazo-1-naphthol-3, 6-disulfonic acid Alizurol purple SS. 60725 I-hydroxy-4-p-tolhuno-anthraquinone.
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1 2 3 .Acid Red 89. 23910 ---- Acid Red 97. . 22890 ---- Acid Blue 1 42045 ---- Food Blue 3 42045 ---- Natural Orange 75480 ---- Solvent Blues 4 44045 ---- Solvent Yellow 18 12740 ---- Food Yellow 18. 12740 ---- Solvent Red 1. 12150 ---- Solvent Yellow 32. 48045 ---- Fanchon Yellow (Hansa Yellow G).
11680 (a) (o-Nitro-p-tolylazo) accetoacetanilide
1[Part II – List of Colours permitted to be used in Soaps.
Phthalocyanine Blue 74160 (phthalocyninate (2--) copper
Iragalite Red CVPB Paste or Pigment Orange 5
12075 1-(2,4-dinithro phenylazo-2-Naphthalenol.
Citrus Red No.2. 12156 1-2(2,5-dimethoxy phenylazo) 2-naphthol. Rhodamine B 500 45170 3-ethochloride of 9-0 carboxy-ethenyl-6-diethylamino-
3-ethylamine-3-isoxanthene. Aqueous Green Paste 74260 Polychloro copper Phthalocyanine.
Pigment Yellow 3 11710 2-(4-Chloro-2-nitrophenyl)-azo-N-(-2-Chlorophenyl)- 3-Oxobutamide.
Irgalite Carmine F-P Power or Pigments Red 5.
12490 N-(5-Chloro-2, 4-dimethoxy-phenyl)-4-(CS-diathy- lamine) Sulfonyl-2-methoxyphenyl)azo-3-hydroxy-2- naphthalene carboxamide.
Monolite Red 4R HV Paste or Pigment Red 7.
12420 N-(4-Chloro-2-methylphenyl-4-(-4-Chloro-2- methylphenyl) azo 3-hydroxy-2-naphthalenel Carboxamide.
Oil Red No.1 or Solvent Red 24 or Oil Red 3R.
26105 4-0-Tolylazo-Toluidine azo 2-naphthalenol.]
_____________________________________________________________________________ 1 Ins. by G.O.I. Notification No. GSR 11(E) dt 7.1.1991.
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1[SCHEDULE R
[See Rule 125]
Standards for condoms made of rubber latex intended for single use and other mechanical contraceptives.
I-Condoms
1. Description. -Condoms consist of cylindrical rubber sheaths with one end open. The open end shall terminate with an integral rim. The closed end may have a receptacle. They may be supplied rolled and shall be free from tackiness and shall be capable of being unrolled readily.
2. Materials. - (1) Condoms shall be manufactured from good quality rubber latex and shall be free from embedded grit and shall be opaque or translucent prior to the application of dusting materials or lubricants;
(2) The rubber latex, colours used and any dusting materials or lubricants applied to the condoms shall neither contain nor liberate substances which are known to have toxic or other harmful effects under normal conditions of use. Any dusting material or lubricant or colour used shall not have deleterious effect on the condoms or be harmful to the users.
3. Procedure for sampling during production. - (1) Specimens constituting the test samples shall be taken at random successively from each quantum of production that is, from the quantity produced from the same finished rubber latex and under the same processing and finishing conditions of manufacture and samples from each quantum shall be tested separately to ascertain conformity of quantum with the specified requirements in accordance with the tests described in this Schedule.
(2) (a) The number of samples drawn from each quantum shall be not less than 0.5 per cent of the number.
(b) The number of samples drawn from each quantum shall be tested for Burst Volume and Pressure Test and Water Leakage Test in accordance with the method prescribed in paras 9 and 10 of this Schedule; 75 per cent of the samples drawn will be tested for Water Leakage Test and 25 per cent will be tested for Burst Volume and Pressure Test.
(c) The number of test samples ‘N’ and the number of rejected samples ‘R’ from a sequence of production quanta shall be recorded in a register. The cumulative total of test samples
_____________________________________________________________________________ 1Subs, by G.O.I. Notification No. GSR 495(E) dt 9.6.1995
562
‘N’ and the cumulative total of rejects ‘R’ from the test shall be recorded and the condoms shall be deemed to comply with the requirements if the cumulative total of rejects ‘R’ is not more than 2[0.0025N+3 x v0.0025N] for Water Leakage Test, and 3[0.01N+3 x v0.01N] for Burst Volume and Pressure Test.
(3) Each unit of 100 test samples shall be distributed for the various tests and follows: -
25 for Burst Volume Pressure Test, and; 75 for Water Leakage Test
(4) Where the number of test samples is a multiple of 100 the distribution scale mentioned above shall be prorated.
(5) If the cumulative total sample rejected exceeds the number of allowables at any point in the sequence of quanta, the quantum at which this occurs shall be liable to rejection. The assessment of quality of further production quanta shall include all previous test results starting from quantum number 1 and approval of production shall be in suspense until the condition required by the scheme is again fulfilled.
(6) At least one sample shall be taken at random from each production quantum not exceeding 10,000 condoms and shall satisfy all requirements regarding dimensions as specified in paragraph 8 of this Schedule.
4. Procedure for sampling and testing of finished products by a manufacturer-
A. Water Leakage Test.- (1) Statistical sampling for quality control assessment of the finished product in respect of Water Leakage Test shall be done in accordance with the plan set out in Annexure 1 to this Schedule.
(2) A test sample failing in the above test is to be considered as defective. If the cumulative total of rejects ‘R’ is found to be equal to or greater than the number shown against ‘R’ in Annexure-I, the batch or lot shall be declared as not of standard quality.
B. Bursting Volume and Pressure Test.- (1) Sample condoms shall be tested for Bursting Volume and Pressure Test. Statistical sampling for this test shall be done in accordance with the plan set out in Annexure III to this Schedule.
Condoms shall not leak or burst at a volume of less than that specified or at a pressure less than 1.0 kpa (gauge), when tested as per paragraph 9, both before and after oven conditioning as specified in annexure V. Bursting Volume minimum limit in litres shall be equal to [mean condom width (mm) 2] rounded to the nearest 0.5 litre.
151.8
563
(2) A test sample failing in the above test is to be considered defective. If the cumulative total of rejects ‘R’ is found to be equal or greater than the number shown against ‘R’ in annexure III, the batch or lot shall be declared as not of standard quality.
C. Dimensions. - At least 2 samples drawn from the lot or batch shall satisfy the requirements regarding Dimensions as specified in paragraph 8 of the Schedule.
5. Procedure for sampling and testing of condoms by a purchaser.-
A. Water Leakage Test.- (1) Statistical sampling of condoms by a purchaser for Water Leakage Test shall be done in accordance with the plan set out in annexure II to this Schedule;
(2) A test sample failing in the above test is to be considered as defective. If the cumulative total of rejects ‘R’ is found to be equal to or greater than the number shown against ‘R’ in the Annexure-II, the batch or lot shall be declared as not of standard quality.
B. Bursting Volume and Pressure Test.- Sample condoms shall be tested for Bursting Volume and Pressure Test. Statistical sampling for this test shall be done in accordance with the plan set out in Annexure III to this Schedule. If the cumulative total of rejects ‘R’ is found to be equal to or greater that the number shown against ‘R’ in Annexure III, the batch or lot shall be declared as not of standard quality.
Condom shall not leak or burst at a volume of less than that specified or at a pressure less than 1.0 kpa (gauge), when tested as specified in paragraph 9, both before and after oven conditioning as per specified in Annexure V. Bursting volume minimum limit in litres shall be equal [mean condom width (mm) 2] rounded to the nearest 0.5 litre.
151.8 Dimensions. - At least two samples from the lot or batch shall satisfy the requirements
regarding dimensions as specified in paragraph 8 of this Schedule.
6. Sampling plan for a Drugs Inspector. - (1) Where an Inspector under the Act, desires to take for test samples from the premises of manufacturer or a distribution depot; twenty containers from each batch of production may be selected by him on a random basis and from each of this containers, five samples shall be taken. The hundred samples so selected shall be distributed for various tests as specified in paragraph 7 of this Schedule. In case the number of container is less than twenty, the number of samples to be taken from each container shall be proportionately increased.
(2) Where an Inspector under the Act, desires to take samples from a sales premises, he shall take hundred samples from each batch of production in accordance with the procedure as specified in sub-paragraph (1).
7. Sampled condoms drawn under sub-paragraph (1) shall be distributed for various tests as follows: -
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Two samples for thickness, length and width;
Forty-five samples for Water Leakage Test;
Forty-five samples for Bursting Volume and Pressure Test; and
Eight samples as reserve.
The samples shall be declared as not of standard quality, if, - (i) the number of condoms found defective in the Water Leakage Test exceeds one; (ii) the number of condoms found defective in Bursting Volume and Pressure Test exceeds two; (iii) samples fail to conform to the requirements of dimensions as specified in paragraph 8 of this Schedule.
8. Dimensions. - (1) the length when unrolled (excluding teat) shall be not less than. -
(i) 170mm (ii) 180 mm
(2) The width of a condom which laid flat and measured at any point within 85 mm from the open end shall be,
(i) 49 ± 2mm for 170mm length (iii) 52 ± 2mm for 180mm length.
(3) The single-wall thickness of a condom when measured at three points, one at 30 ± 2mm from the open end, 30 ± 5mm from the close end excluding the reservoir tip and at the mid distance between these two point shall be from 0.045 mm to 0.075 mm.
NOTE 1. - The single-wall thickness shall be determined with a suitable micrometer dial gauge graduated in intervals of 0.01 mm.
NOTE 2. - Condoms shall, prior to the measurement of thickness, have the dusting powder or the lubricant or both removed by means of water or Isopropanol.
9. Bursting Volume and Pressure Test.- Determination of Bursting Volume and Pressure Test shall be done as specified in Annexure IV.
10. Water Leakage Test.- Unroll the condom and fit the open end on a suitable mount, the condom thus being suspended open end upwards. Fill it with 300ml water at room temperature and inspect it after a period of at least 1 minute for leakage up to 25mm from the open end because of distension of the condom the water does not extend to25mm from the open end. If raise the closed end until the water level reaches this distance. After at least 1 minute, inspect the newly-wetted part of the condom for leakage. The condom shall be deemed to be defective if it
565
bursts during test or shows any evidence of leakage or seepage of micro-droplets or does not hold 300ml water.
11. Quantity of Lubricant. -(1) The condoms shall be dressed with silicone lubricant. The quantity required on each individual condom should not be less than 200 mg and minimum viscosity shall be 200 centistokes.
(2) Lubricated condoms in individual foil packages shall be weighed on an Analytical Balance. Each condom shall be removed from its foil package and both condom and its foil package shall be washed in denatured ethanol or isopropanol, dried and then weighed again. All weights shall be recorded to the nearest milligram (mg.). Compliance with the requirement shall be determined by subtracting the weight of the washed and dried condom and its foil package from the weight of sample condom in individual foil package prior to the removal of lubricant. Washing and drying may be required upto a total of four times if the lubricant quantity is less than the required minimum.
(3) At least thirteen samples shall be drawn from the lot or batch and the samples shall satisfy the requirements regarding the quantity of lubricant.
12. Colour Fastness.- Not less than ten samples taken at random from each batch of coloured condoms shall pass the following test for colour fastness, namely :-
Thoroughly wet inside and outside of the condom with distilled water. Make no attempt to remove any dusting material or lubricant. Wrap the wet condom in white absorbent paper so that the largest possible surface area of the condom is in contact with the paper and seal the whole in a suitable container to prevent loss of moisture. Allow the container and its contents to stand for 16 hours to 24 hours at room temperature. After removing the absorbent paper from the container, examine it visually the natural daylight for any indication of staining. No part of the absorbent paper shall be stained. If there is any indication of staining of the absorbent paper by any colouring agent present in any of the condoms or any dusting material or lubricant, the entire batch shall be declared to be not of standard quality.
13. Labelling, packing and storage. - (1) The condoms shall be individually wrapped and sealed in laminates containing at least eight microns of aluminium foil. The individual condom shall be packed in square (non-squeeze condition) / rectangular aluminium foil. The packing shall protect the condoms from contamination and mechanical damage. The smallest packing offered to the consumer shall bear a clear permanent marking with the following particulars, namely: -
(i) Manufacturer’s name and address and the trade name of the condoms, if any;
(ii) Batch number; (iii) Date of manufacture (Month and year only); (iv) Date of expiry (Month and year only) which shall not be more than thirty-
six months from the date of manufacture;
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(v) The words “For single use only”
(2)The condoms shall be stored in a cool dry place away from heat and direct sunlight.
14. Integrity of individual package seals. - Sample condoms in individual packages shall be placed in a sealed, transparent container (such as a laboratory Bell jar) and subjected to vacuum of 50± 10 kpa (gauge) for a period one minute.
Condom packages that do not inflate or remain inflated for the period of the test shall be deemed non-compliers. In doubtful cases, the test may be repeated, and both the inflation and deflation of packages may be observed on application and removal of vacuum. An AQL of 2.5 per cent will be applied in assessing the results of this test. Thirty-two samples of condoms for a batch size less than 5 lakhs and fifty samples of condoms for batch size more than 5 lakhs shall be tested for integrity test of individual package seals and compliance limit or acceptance number shall be not more than two or three condoms respectively.
II- Other Mechanical Contraceptive
15. Standards for other mechanical contraceptive - Standards for ‘Copper T’ and ‘Tubal Ring’ shall be as laid down in Annexure VI.
*[ANNEXURE I
[See Paragraph 4-A]
Sampling Plan for Quantity Control of Condoms at Manufacturer’s Level.
BATCH SIZE: 35,001 TO 1.5 LAKH. Single Sampling Plan. Sample Size 200: AQL - 0.25
AC - 1 R - 2
BATCH SIZE: 150001 TO 5 LAKHS Single Sampling Plan. Sample Size 315 : AQL - 0.25
AC - 2 R - 3
* Annexures I to III subs. by G.O.I. Notification No. GSR 353(E) dt 26-4-2000.
567
BATCH SIZE: OVER 5 LAKHS
Single Sampling Plan. Sample Size 500: AQL - 0.25
AC - 3 R - 4
Note : AQL denotes Acceptance Quality Level; AC denotes Acceptance Number i.e. the maximum allowable number of defectives for acceptance of the Batch; and R denotes Rejection Number i.e., the minimum number of defectives for rejection of the Batch.
ANNEDURE II
[See Paragraph 5-A]
Sampling Plan for Quality Control of Condoms at Purchaser’s Level.
BATCH SIZE: 35,001 TO 1.5 LAKHS Single Sampling Plan. Sample Size 200: AQL - 0.25
AC - 1 R - 2
BATCH SIZE : 15,001 TO 5 LAKHS Single Sampling Plan. Sample Size 315: AQL - 0.25
AC - 2 R - 3
BATCH SIZE : OVER 5 LAKHS Single Sampling Plan. Sample Size 500: AQL - 0.25
AC - 3 R - 4
Note: AQL denotes Acceptance Quality Level; AC denotes Acceptance Number i.e. the maximum allowable number of defectives
for acceptance of the Batch; and R denotes Rejection Number i.e., the minimum number of defectives for rejection
of the Batch.
568
ANNEXURE III
[See Paragraph 4-B and 5-B]
Sampling Plan for Bursting Volume and Pressure Test.
BATCH SIZE: 35,001 TO 1.5 LAKH. Single Sampling Plan. Sample Size 200: AQL - 1.5
AC - 7 R - 8
BATCH SIZE: 150001 TO 5 LAKHS Single Sampling Plan. Sample Size 315: AQL - 1.5
AC - 10 R - 11
BATCH SIZE: OVER 5 LAKHS Single Sampling Plan. Sample Size 500: AQL - 1.5
AC - 14 R - 15
Note : AQL denotes Acceptance Quality Level; AC denotes Acceptance Number i.e. the maximum allowable number of defectives
for acceptance of the Batch; and R denotes Rejection Number i.e., the minimum number of defectives for rejection
of the Batch.]
ANNEXURE IV
(See Paragraph 9) Determination of Bursting Volume and Pressure.
1. Principle. - Inflation of constant length of the condom with air and recording the volume and pressure at the moment of bursting.
2. Apparatus. - (1) Apparatus suitable for inflating the condom with clean air at a specified rate and provided with equipment for measuring volume and pressure.
(2) Suitable mount for fitting the condoms to the apparatus as shown in the figure annexed.
(3) Rod, 140mm in length having a smooth sphere 20 mm in diameter at its top (see the figure) for hanging the unrolled condom when fixed to the apparatus.
569
3. Procedure. - (1) Unroll the condom, hang it on the rod (2.3), affix to the mount (2.2) and inflate with air at a rate of 0.4 to 0.5 litre/sec. (24 to 30 litres/min)
(2) Measure and note the Bursting Volume, in litres rounded to the nearest 0.5 litre and the bursting pressure, in kilopascals rounded to the nea5rest 0.1 kpa.
4. Test report. - The test report shall include the following particulars. (a) the identification of the sample, (b) the Bursting Volume and Bursting Pressure of each tested condom; (c) the date of testing.
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ANNEXURE V
[See Paragraphs 4(B) and 5 (B)
Oven Conditioning
1. Principle of the Method. - The test consists in subjecting test samples to controlled deterioration by air at an elevated temperature and at atmospheric pressure after which Burst Volume and Pressure limits are measured.
2. Apparatus. - The air oven shall be of such a size that the total volume of the test samples does not exceed 10 per cent of the free air space of the oven. Provision shall be made for slow circulation of air in the oven of not less than three changes and not more than ten changes per hour. The temperature of the over shall be thermostatically controlled so that the test samples are kept within ± 2 oC of the specified ageing temperature. A thermometer shall be placed near the center of the ageing test samples to record the actual ageing temperature.
Note: - Copper or Copper alloys shall not be used for the material of construction of the oven prescribed.
3. Test sample. - The foil laminations of individual packages should remain intact throughout all laboratory handling including over conditioning.
4. Temperature of the oven – Maintain the over at 70 ± 2 oC.
5. Duration of test. - 96 hours.
6. Procedure. - Condition the requisite number of unopened packages of rubber condoms in the oven at 70 ± 2 oC for 96 hours. After heating, keep the packages at 23 ± 5 oC for at least 12 hours but not more than 96 hours. Open the packages and examine conditioned condoms for thickness, brittleness, or other signs of deterioration. Within 96 hours but not sooner than 12 hours after conditioning, do the Bursting Volume and Pressure Test as described in this Schedule.
ANNEXURE VI
(See Paragraph 15)
1. Standards for Copper T (200B) (IS-12418 (part 4)-1991-UDC 615.477.87. - Contraceptive Device Copper T (200B) shall conform to the Indian Standards laid down from time to time b the Bureau of Indian Standards.
2. Standards for Contraceptive Tubal Ring (IS 13009 : 1990-UDC 615.472.6 : 611.656).- Contraceptive Device Tubal Ring shall conform to the Indian Standards laid down from time to time by the Bureau of Indian Standards.]
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1[SCHEDULE R-1
(See Rules 109-A and 125-A)
The following medical device shall conform to the Indian Standards specification laid down from time to time by the Bureau of Indian Standards: -
(1) Sterile Disposable Perfusion sets for single use only (Sections 2 and 3 of item 1 of IS 9824:1981 read with Amendment number 1).
(2) Sterile Disposable Hypodermic Syringes for single use only (IS 10258 : 1982).
(3) Sterile Disposable Hypodermic Needles for single use only 9IS 10654 : 1991)]
2[SCHEDULE S
[See Rule 150-A]
STANDARDS FOR COSMETICS
Standards for cosmetics in finished form.- The following cosmetics in finished form shall conform to the Indian Standards specifications laid down from time to time by the 3[Bureau of Indian Standards (BIS)].
1. Skin Powders 2. Skin Powder for infants 3. Tooth Powder 4. Toothpaste 5. Skin Creams 6. Hair Oils 7. Shampoo, Soap-based 8. Shampoo, Synthetic-Detergent based 9. Hair Creams 10. Oxidation hair dyes, Liquid 11. Cologne.]
3[12 Nail Polish (Nail Enamel) 13. After Shave Lotion 14. Pomades and Brilliantines 15. Depliatories chemicals
1Ins. by G.O.I. Notification No. GSR 510(E) dt 26.7.1982. 2 Subs. by G.O.I. Notification No. GSR 673(E) dt 27.10.1993. 3Added by G.O.I. Notification No. GSR 731(E) dt 28.8.1990
572
16 Shaving Creams 17. Cosmetic Pencils 18. Lipstick]
1[19. Toilet Soap 20. Liquid Toilet Soap 21. Baby Toilet Soap 22. Shaving Soap 23. Transparent Toilet Soap]
2[24. Lipsalve IS:10284 25. Powder Hair Dye IS: 10350 26. Bindi (Liquid) IS: 10998 27. Kum Kum Powde IS: 10999 28. Henna Powder IS: 11142]
3SCHEDULE T
[See Rule 157] GOOD MANUFACTURING PRACTICES FOR AYURVEDIC,
SIDDHA AND UNANI MEDICINES.
The Good Manufacturing Practices (GMP) are prescribed as follows in Part I and Part II to ensure: -
i) raw materials used in the manufacture of drugs are authentic, of prescribed quality and are free from contamination;
ii) the manufacturing process is as has been prescribed to maintain the standards; iii) adequate quality control measures are adopted; iv) the manufactured drug which is released for sale is of acceptable quality; v) to achieve the objectives listed above, each licensee shall evolve methodology and
procedures for following the prescribed process of manufacture of drugs which should be documented as a manual and kept for reference and inspection. However, under IMCC Act 1970 registered Vaidyas, Siddhas and Hakeems who prepare medicines on their own to dispense to their patients and not selling such drugs in the market are exempted from the purview of Good Manufacturing Practices (GMP).
PART I
GOOD MANUFACTURING PRACTICES
Factory Premises: The manufacturing plant should have adequate space for: -
____________________________________________________________________________ 1Ins. by G.O.I. Notification No. GSR 673(E) dt 27.10.1993. 2Ins. by G.O.I. Notification No. GSR 553(E) dt 20.7.1995. 3 Sub. By G.O.I. Notification No. GSR 198(E) dt 07.3.2003.
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(i) receiving and storing raw material; (ii) manufacturing process areas; (iii)Quality control section; (iv)finished goods store; (v) office; (vi)rejected goods/drugs store.
1.1.General Requirements:
1.1(A) Location and surroundings. - The factory building for manufacture of Ayurveda, Siddha and Unani medicines shall be so situated and shall have such construction as to avoid contamination from open sewerage, drain, public lavatory for any factory which produces disagreeable or obnoxious odour or fumes or excessive soot, dust and smoke.
1.1(B) Buildings. - The buildings used for factory shall be such as to permit production of drugs under hygienic conditions and should be free from cobwebs and insects/rodents. It should have adequate provision of light and ventilation. The floor and the walls should not be damp or moist. The premises used for manufacturing, processing, packaging and labeling will be in conformity with the provisions of the Factory Act. It shall be located so as to be:
(I) Compatible with other manufacturing operations that may be carried out in the same or adjacent premises.
(II) Adequately provided with working space to allow orderly and logical placement of equipment and materials to avoid the risk of mix up between different drugs or components thereof and control the possibility of cross contamination by other drugs or substances and avoid the risk of omission of any manufacturing or control step.
(III) Designed, constructed and maintained to prevent entry of insects and rodents. Interior surface (walls, floors and ceilings) shall be smooth and free from cracks and permit easy cleaning and disinfection. The walls of the room in which the manufacturing operations are carried out shall be impervious to and be capable of being kept clean. The flooring shall be smooth and even and shall be such as not to permit retention or accumulation of dust or waste products.
(IV) Provided with proper drainage system in the processing area. The sanitary fittings and electrical fixtures in the manufacturing area shall be proper and safe.
(V) Furnace/Bhatti section could be covered with tin roof and proper ventilation, but sufficient care should be taken to prevent flies and dust.
(VI) There should be fire safety measures and proper exits should be there. (VII) Drying Space: - There should be separate space for drying of raw materials, in
process medicine or medicines require drying before packing. This space will be protected from flies/ insects/ dust etc., by proper flooring, wire mesh window, glass panels or other material.
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1.1(C) Water Supply. - The water used in manufacture shall be pure and of potable quality. Adequate provision of water for washing the premises shall be made.
1.1(D) Disposable of Waste. - From the manufacturing section and laboratories the waste water and the residues which might be prejudicial to the workers or public health shall be disposed off. .
1.1(E) Container’s Cleaning. - In factories where operations involving the use of containers such as glass bottles, vials and jars are conducted, there shall be adequate arrangements separated from the manufacturing operations for washing, cleaning and drying of such containers.
1.1(F) Stores. - Storage should have proper ventilation and shall be free from dampness. It should provide independent adequate space for storage of different types of material, such as raw material, packaging material and finished products.
1.1. (F)(A) Raw Materials. - All raw materials procured for manufacturing will be stored in the raw materials store. The manufacture based on the experience and the characteristics of the particular raw material used in Ayurveda, Siddha and Unani system shall decide the use of appropriate containers which would protect the quality of raw materials as well as prevent it from damage due to dampness, microbiological contamination or rodent and insect infestation, etc. If certain raw materials require such controlled environmental conditions, the raw materials stores may be sub-divided with proper enclosures to provide such conditions by suitable cabinization. While designing such containers, cupboard or areas in the raw materials store, care may be taken to handle the following different categories of raw materials:-
1. Raw material of metallic origin. 2. Raw material of mineral origin 3. Raw material from animal source 4. Fresh Herbs 5. Dry Herbs or Plant parts 6. Excipients etc 7. Volatile oils/perfumes and flavours 8. Plant concentrates/ extracts and exudates/resins.
Each container used for raw material storage shall be properly identified with the label which indicates name of the raw material, source of supply and will also clearly state the status of raw material such as ‘UNDER TEST’ or ‘APPROVED’ or ‘REJECTED’. The labels shall further indicate the identity of the particular supply in the form of Batch No. or Lot No. and the date of receipt of the consignment.
All the raw materials shall be sampled and got tested either by the in-house Ayurvedic, Siddha and Unani experts (Quality control technical person) or by the laboratories approved by the Government and shall be used only on approval after verifying. The rejected raw material should
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be removed from other raw material store and should be kept in separate room. Procedure of ‘First in first out’ should be adopted for raw materials wherever necessary. Records of the receipt, testing and approval or rejection and use of raw material shall be maintained.
1.1. (F)(B) Packing Materials. - All packaging materials such as bottles, jars, capsules etc. shall be stored properly. All containers and closure shall be adequately cleaned and dried before packing the products.
1.1. (F)(C) Finished Goods Stores. - The finished goods transferred from the production area after proper packaging shall be stored in the finished goods stores within an area marked “Quarantine”. After the quality control laboratory and the experts have checked the correctness of finished goods with reference to its packing/labeling as well as finished product quality as prescribed, then it will be moved to “Approved Finished Goods Stock” area. Only approved finished goods shall be dispatched as per marketing requirements. Distribution records shall be maintained as required.
If any Ayurvedic, Siddha and Unani drug needs special storage conditions, finished goods store shall provide necessary environmental requirements.
1.1(G) Working space. - The manufacturing area shall provide adequate space (manufacture and quality control) for orderly placement of equipment and material used in any of the operations for which these employed so as to facilitate easy and safe working and to minimize or to eliminate any risk of mix-up between different drugs, raw materials and to prevent the possibility of cross contamination of one drug by another drug that is manufactured, stored or handled in the same premises.
1.1(H) Health Clothing, Sanitation and Hygiene of Workers.- All workers employed in the Factory shall be free from contagious diseases. The clothing of the workers shall consist of proper uniform suitable to the nature of work and the climate and shall be clean. The uniform shall also include cloth or synthetic covering for hands, feet and head wherever required. Adequate facilities for personal cleanliness such as clean towels, soap and scrubbing brushes shall be provided. Separate provision shall be made for lavatories to be used by men and women, and such lavatories shall be located at places separated from the processing rooms. Workers will also be provided facilities for changing their clothes and to keep their personal belongings.
1.1. (I) Medical Services: The manufacturer shall also provide:-
(a) Adequate facilities for first aid;
(b) Medical examination of workers at the time of employment and periodical check up thereafter by a physician once a year, with particular attention being devoted to freedom from infections. Records thereof shall be maintained.
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1.1(J) Machinery and Equipments. - For carrying out manufacturing depending on the size of operation and the nature of product manufactured, suitable equipment either manually operated or operated semi-automatically (Electrical or steam based) or fully automatic machinery shall be made available. These may include machines for use in the process of manufacture such as crushing, grinding powdering, boiling, mashing, burning, roasting, filtering, drying, filling, labeling and packing etc. to ensure case in movement of workers and orderliness in operation a suitably adequate space will be ensured between two machines or rows of machines. These equipments have to be properly installed and maintained with proper cleaning. List of equipments and machinery recommended is indicated in Part II A.
Proper Standard Operational Procedures (SOPs) for cleaning, maintaining and performance of every machine should be laid down.
1.1(K) Batch Manufacturing Records. - The licencee shall maintain batch manufacturing record of each batch of Ayurvedic, Siddha and Unani drugs manufactured irrespective of the type of product manufactured (classical preparation or patent and proprietary medicines). Manufacturing records are required to provide an account of the list of raw materials and their quantities obtained from the store, tests conducted during the various stages of manufacture like taste, colour, physical characteristics and chemical tests as may be necessary or indicated in the approved books of Ayurveda, Siddha and Unani mentioned in the First Schedule of the Drugs and Cosmetics Act, 1940 (23 of 19400. These tests may include any in-house or pharmacopoeial test adopted by the manufacturer in the raw material or in the process material and in the finished product. These records shall be duly signed by Production and Quality Control Personnel respectively. Details of transfer of manufactured drug to the finished products store including dates and quantity of drugs transferred along with record of testing of the finished product, if any, and packaging, records shall be maintained. Only after the manufactured drugs have been verified and accepted quality shall be allowed to be cleared for sale.
It should be essential to maintain the record of date, manpower, machine and equipments used and to keep in process record of various shodhana, Bhavana, burning and fire and specific grindings in terms of internal use.
1.1(L) Distribution Records. - Records of sale and distribution of each batch of Ayurveda, Siddha and Unai Drugs shall be maintained in order to facilitate prompt and complete recall of the batch, if necessary.The duration of record keeping should be the date of expiry of the batch. Ceertain category of Ayurvedic, siddha and Unani medicines like Bhasma, Rasa, Kupi-pakva, Parpati, Sindura, Karpu/uppu/puram, kushta, Asava-arishta etc. do not have expiry date in contrast their efficiency increases with the passage of time. Hence, records need be maintained upto five years of the exhausting of stock.
1.1(M) Record of Market Complaints. - Manufacturers shall maintain a register to record all reports of market complaints received regarding the products sold in the market. The manufacturer shall enter all data received on such market complaints, investigations carried out by
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the manufacturers regarding the complaint as well as any corrective action initiated to prevent recurrence of such market complaints shall also be recorded. Once in a period of six months the manufacturer shall submit the record of such complaints to the licensing authority. The Register shall also be available for inspection during any inspection of the premises.
Records of any adverse reaction resulting from the use of Ayurvedic, Siddha and Unani drugs shall also be maintained in a separate register by each manufacturer. The manufacturer shall investigate any of the adverse reaction to find if the same is due to any defect in the product, and whether such reactions are already reported in the literature or it is a new observation.
1.1(N) Quality Control. - Every licensee is required to provide facility for quality control section in his own premises or through Government approved testing laboratory. The test shall be as per the Auurveda, Siddha and Unani pharmacopoeial standard. Where the tests are not available, the test should be performed according to the manufacturers specification or other information available. The quality control section shall verify all the raw materials, monitor in process, quality checks and control the quality of finished product being released to finished goods store/warehouse. Preferably for such Quality control there will be a separate expert. The quality control section shall have the following facilities: -
1) There should be 150 sq. feet area for quality control section. 2) For identification of raw drugs, reference books and reference samples should be
maintained. 3) Manufacturing record should be maintained for the various processes. 4) To verify the finished products, controlled samples of finished products of each
batch will be kept for 3 years. 5) To supervise and monitor adequacy of conditions under which raw materials, semi-
finished products and finished products are stored. 6) Keep record in establishing shelf life and storage requirements for the drugs. 7) Manufacturers who are manufacturing patent proprietary Ayurveda Siddha, and
Unani medicines shall provide their own specification and control reference in respect of such formulated drugs.
8) The record of specific method and procedure of preparation, that is, “Bhavana”, “Mardana” and “Puta” and the record of every process carried out by the manufacturer shall be maintained.
9) The standards for identity, purity and strength as given in respective pharmacopoeias of Ayurveda, Siddha and Unani systems of medicines published by Government of India shall be complied with.
10) All raw materials will be monitored for fungal, bacterial contamination with a view to minimize such contamination.
11) Quality control section will have a minimum of:
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(i) One person with Ayurveda /Siddha/ Unani qualification recognized under Schedule II of Indian Medicine Central Council Act, 1970 (84 of 1970). Two other persons one each with Bachelor qualification in Botony/ Chemistry/ Pharmacy could be on part time or contractual basis.
(ii) The manufacturing unit shall have a quality control section as explained under Section 35(ii). Alternatively, these quality control provisions will be met by getting testing etc., from a recognized laboratory for Ayuveda, Siddha and Unani drugs; under Rule 160-A of the Drugs and Cosmetics Act. The manufacturing company will maintain all the record of various tests got done from outside recognized laboratory.
(iii)List of equipments recommended is indicated in Part II C.
1.2. Requirement for Sterile Product: .2(A) Manufacturing Areas: For the manufacture of sterile Ayurvedic, Unani and Siddha
drugs, separate enclosed areas specifically designated for the purpose shall be provided. These areas shall be provided with air locks for entry and shall be essentially dust free and ventilated with an air supply. For all areas where aseptic manufacture has to be carried out, air supply shall be filtered through bacteria retaining filters (HEPA Filters) and shall be at a pressure higher than in the adjacent areas. The filters shall be checked for performance on installation and periodically thereafter the record of checks shall be maintained. All the surfaces in sterile manufacturing areas shall be designed to facilitate cleaning and disinfection. For sterile manufacturing routine microbial counts of all Ayurvedic, Siddha and Unani drug manufacturing areas shall be carried out during operations. Results of such count shall be checked against established in-house standards and record maintained.
Access to manufacturing areas shall be restricted to minimum number of authorized personnel. Special procedure to be followed for entering and leaving the manufacturing areas shall be written down and displayed.
For the manufacturing of Ayurvedic, Siddha and Unani drug that can be sterilized in their final containers, the design of the areas shall be preclude the possibility of the products intended for sterilization being mixed with or taken to be products already sterilized. In case of terminally sterilized products, the design of the areas shall preclude the possibility of mix up between non- sterile products.
1.2(B) Precautions against contamination and mix:
(a) Carrying out manufacturing operations in a separate block of adequately isolated building or operating in an isolated enclosure within the building,
(b) Using appropriate pressure differential in the process area. (c) Providing a suitable exhaust system. (d) Designing laminar flow sterile air system for sterile products.
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(e) The germicidal efficiency of UV lamps shall be checked and recorded indicating the burning hours or checked using intensity.
(f) Individual containers of liquids and ophthalmic solutions shall be examined against black-white background fitted with diffused light after filling to ensure freedom from contamination with foreign suspended matter.
(g) Expert technical staff approved by the Licensing Authority shall check and compare actual yield against theoretical yield before final distribution of the batch.
All process controls as required under master formula including room temperature, relative humidity, volume filled, leakage and clarify shall be checked and recorded.
PART II
A. LIST OF MACHINERY, EQUIPMENT AND MINIMUM MANUFACTURING PREMISES REQUIRED FOR THE
MANUFACTURE OF VARIOUS CATEGORIES OF AYURVEDIC, SIDDHA SYSTEM OF MEDICINES.
Sl.No. Category of Medicine Minimum manufacturing space required
Machinery/equipment recommended
(1) (2) (3) (4)
1200 Square feet covered area with separate cabins partitions for each activity. If Unani medicines are manufactured in same premises an additional area of 400 sq. feet will be required.
1. Anjana/Pisti 100 sq. feet. Karel/mechanized/motorized, kharel. End runner/Ball-Mill Sieves/Shifter
2. Churna / Nasya Manjan/Lepa Kwath Churn
200 Sq feet Grinder / disintegrator / Pulverisar / Powder mixer / Sieves / Shifter.
3. Pills / Vatti / Gutika Matrica and tablets
100 sq. feet Ball Mill, Mass mixer powder mixer, granulator, drier, tablet compressing machine, pill/vati cutting machine, stainless steel trays/container for storage and sugar coating, polishing pan in the case of sugar coated
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tablets,mechanised chattoo (for mixing guggulu) where required.
1 2 3 4
4. Kupi pakava / Ksara / Parpati / Lavana Bhasma Satva / Sindura Karpu / Uppu / Param
150 Sq. feet Bhatti,Karahi/StainlessSteelVessels/ Patila Flask, Multani Matti/Plaster of Paris, copper Rod, Earthern container, GajPutBhatti,Mufflefurnace(Electri- callyoperated)End/EdgeRunner,Exhaus tFan,Wooden/S.S.Spatula.
5. Kajal 100 Sq. feet Earthern lamps for Collection of Kajal, Triple Roller Mill, End Roller, Sieves, S.S.Patila, filling / packing and manufacturing room should be provided with exhaust fan & ultra violet lamps.
6. Capsules 100 Sq. feet Air Conditioner, De humidifier, hygrome ter, thermometer, Capsule filling machine and chemical balance.
7. Ointment /Marham / Pasai
100 Sq. feet Tube filling machine, Crimping machine/Ointment mixer, End Runner/ Mill (Where required) S.S. Storage Container S.S.Patila.
8. Pak /Avalesh / Khand / Modak /Lakayam
100 Sq. feet Bhatti section fitted with exhaust fan and should be fly proof, iron kadahi / S.S.Patila and S.S. Storage container.
9. Panak / Syrup / Pravahi Kwath Manapaku
150 Sq, feet Tincture press, exhaust fan fitted and fly proof, Bhatti section, Bottle washing machine, filter press / Gravity filter liquid filling machine, P.P. Capping Machine.
10. Asava / Arishta 200 Sq. ft Same as mentioned above. Fermentation tanks containers and distillation plant where necessary, Filter Press.
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12. Sura 100 Sq. ft Same as mentioned above plus distillation plant and transfer pump.
13. Ark/ Tinir 100 Sq. ft Maceration tank, Distillation plant, Liquid filling tank with tap / Gravity filter/Filter press, Visual inspection box.
14. Tail/Ghrit Ney 100 Sq. ft Bhatti, Kadahi/S.S. Patila S.S.Storage Containers, Filtration equipment, filling tank with tap/Liquid filling machine.
15. Aschyotan / Netra Malham Panir
100 Sq. ft Hot air oven electrically heated with thermostatic control, kettle gas or electrically heated with suitable mixing arrangements collation mill, or ointment mill, tube filling equipment, mixing and storage tanks of stainless steel or of other suitable material sintered glass funnel, seitz filter or filter candle, liquid filling equipment, autoclave.
16. Each manufacturing unit will have a separate area for Bhatti, furnace, boilers, puta, etc. This will have proper ventilation, removal of smoke, prevention of flies, insets, dust etc. the furnace section could have tin roof.
200 Sq. ft
B. LIST OF MACHINERY, EQUIPMENT AND MINIMUM MANUFACTURING PREMISES REQUIRED FOR THE MANUFACTURE OF VARIOUS CATEGORIES OF
UNANI SYSTEM OF MEDICINES.
Sl.No. Category of Medicine Minimum manufacturing space required
Machinery/equipment recommended
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(1) (2) (3) (4)
1. 1200 square feet covered area with separate cabins, partitions for each activity. If Ayurveda / Siddha, Medicines are also manufactured in same premises an addition area of 400 square feet will be required.
1. Itrifal Tiryao / majoon / Laooq / Jawarish Khamiras
100 Sq. feet Grinder/ Pulveriser, Sieves, powder mixer (if required), S.S. Patilas, Bhatti and other accessories, Planter mixer for Khamiras.
2. Araq. 100 Sq. feet Distillation Plant (garembic) S.S. storage tank, boiling vessel, gravity filter, bottle filling machine, bottle washing machine, bottle drier.
3. Habb (Pills) and tablets.
100 Sq. feet Ball Mill, Mass Mixer/Powder mixer, Granulator drier, tablet compressing machine, pill/vati cutting machine, stainless steal trays/ container for storage and in the case of sugar coated tablets, mechanized chattoo, (for mixing guggulu) where required.
4. Sufoof (Powder) 100 Sq. feet Grinder / Pulveriser, Sieves, Trays, Scoops, Powder mixer (where required).
5. Raughan (oils) (Crushing and boiling)
100 Sq. feet Oil expeller, S.S. Patilas oil filter bottle, filling machine, bottle drier, bhatti.
6. Shiyaf, Surma, Kajal 100 Sq. feet End runner,mixing S.S. Vessel 7. Marham, Zimad
(Ointment) 100 Sq. feet Karal, Bhatti, End runner, Grinder,
Pulveriser, Triple Roller Mill (if needed).
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(1) (2) (3) (4)
8. Qurs (Tab) 100 Sq. feet Grinder / Pulveriser, Sieves, Powder mixer (where needed), Granulator, Drier, Tablet Compressing Machine, Die punches Trays, D.T. apparatus, Balance with weights, Scoops, Sugar Coating Pan, polishing pan, Heater.
9. Kushta 100 Sq. feet Bhatti, Kharal, Sil Batta, Earthen pots.
10. Murabba 100 Sq. feet. Aluminium Vessels 50-100 kgs. Capacity, Gendna, Bhatti.
11. Capsule 100 Sq. feet Pulveriser, Powder mixer (where needed), capsule filling machine, Air conditioner, Dehumidifier Balance with weights, storage containers, glass.
12. Sharbat & Jushanda 100 Sq. feet Tinctum Press, exhaust fan fitted, Bhatti section, Bottle washing machine, Filter Press, Gravity filter, Liquid filling tank with tap/liquid filling machine, PP capping machine, air over electrically heated with thermostatic control, kettle.
13. Qutoor Chasm and Marham (Eye drops eye ointment)
100 Sq. feet Hot air oven electrically heated with thermostatic control, kettle.
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C. LIST OF EQUIPMENT RECOMMENDED FOR IN HOUSE QUALITY CONTROL SECTION
(alternatively unit can get testing done from the government approved laboratory.)
(A) CHEMISTRY SECTION (B) PHARMACOGNOSY SECTION 1 Alcohol determination Apparatus (complete
set) 1. Microscope Binoculor.
2. Volatile Oil Determination Apparatus. 2. Dissecting Microscope. 3. Boiling Point Determination Apparatus 3. Microtome. 4. Melting Point Determination Apparatus 4. Physical Balance. 5. Refractometer 5. Aluminium Slide Trays. 6. Polarimeter 6. Stage Micrometer. 7. Viscometer. 7. Camera Lucida (Prism and
Mirror Type.) 8. Tablet Disintegration Apparatus. 8. Chemicals, Glass-ware etc. 9. Moisture Meter. 10. Muffle Furnace. 11. Electronic Balance. 12. Magnetic Stirrer. 13. Hot Air Oven. 14. Refrigerator. 15. Glass/Steel Distillation apparatus. 16. LPG Gas Cylinders with Burners. 17 Water Bath(Temperature controlled.) 18 Heating Mantles/ Hot Plates. 19. TLC Apparatus with all accessories
(Manual) 20 Paper Chromatography apparatus with
accessories.
(1) (2) (3) (4)
14. Each manufacturing unit will have a separate area for Bhatti, furnaces, boilers, putta, etc. this will have proper ventilation, removal of smoke, prevention of flies, insets, dust etc.
200 Sq. feet
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21. Sieve size 10 to120 with Sieve shaker. 22 Centrifuge Machine. 23. Dehumidifier. 24 PH Meter. 25. Limit Test Apparatus.
Note: - The above requirements of machinery, equipments, space, qualifications are made subject to the modification at the discretion of the Licensing Authority, if he is of the opinion that having regard to the nature and extent of the manufacturing operations it is necessary to relax or alter then in the circumstances in a particular case.
*[SCHEDULE U
[ see I Rules 74, 74-A, 74-B, 78 and 78-A]
I. PARTICULARS TO BE SHOWN IN MANUFACTURING RECORDS
A. Substances other than parenteral in preparation in general. 1. Serial number
2. Name of the product
3. Reference of Master Formula Records.
4. Lot/Batch Size.
5. Lot/Batch Number
6. Date of commencement of manufacture and date of completion of manufacture and assigned date of expiry.
7. Name of all ingredients, specifications quantities required for the lot/Batch size and quantities actually used. All weighing and measurements shall be carried out by a responsible person and initialed by him and shall be counter-checked and signed by the competent technical staff under whose personal supervision the ingredients are used for manufacture.
8. Control Numbers of raw materials used in the formulation.
9. Date, time and duration of mixing.
10 Details of environmental controls like room temperature, relative humidity.
11.Date of granulation, wherever applicable. _______________________________________________________________________________ * Sub by G.O.I. Notification No. GSR 735(E) dt 24.6.1988.
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12.Theoretical weight and actual weight of granules/powder blend.
13. Records of in-processes controls (Periodically whenever necessary)
a) Uniformity of mixing. b) Moisture content of granules/powder in case of Tablet/Capsules. c) pH of solution in case of liquid. d) Weight variation. e) Disintegration time. f) Hardness g) Friability test h) Leak test in case of strip packing. i) Filled volume of liquids. j) Quantity of tablets/capsules in the final container. k) Content of ointment in the filled containers.
14. Date of compression in case of Tablets/date of filling in case of capsules.
15. Date of sealing/coating /polishing in case of capsules/tablets wherever applicable.
16. Reference to analytical Report number stating the result of test and analysis.
17. Separate records of the disposal of the rejected batches and of batches withdrawn from the market.
18. The theoretical yield and actual productions yield and packing particulars indicating the size and quantity of finished packing.
19. Specimen of label/strip, carton with batch coding information like Batch Number, date of manufacture, date of expiry, retail prices as applicable, stamped thereon and inserts used in the finished packings.
20. Signature with date of competent technical staff responsible for the manufacture.
21. Counter-signature of the head of the testing units or other approved person-in-charge of testing for having verified the batch records and for having released and batch for sale and distribution, the quantity released and date of release.
22. Date of release of finished packings and quantity released for sale and distribution.
23. Quantity transferred to warehouse.
24. For Hypodermic tablets and ophthalmic preparations, which are required to be manufactured under aseptic conditions, records shall be maintained indicating the
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precautions taken during the process of manufacture to ensure that aseptic conditions are maintained.
B. PARENTERAL PREPARATIONS
1. Serial number
2. Name of the product.
3. Reference of the master formula record
4. Batch /Lot size
5. Batch No. and/or Lot No.
6. Date of commenceme nt of manufacture and date of completion.
7. Name of all ingredients, specifications and quantity required for the Lot/Batch size and quantity actually used. All weighings and measurements shall be carried out by a responsible person and initialed by him and shall be countersigned by the technical staff under whose personal supervision the stock are issued and by another competent technical staff under whose supervision the ingredients are used for manufacture.
8. Control numbers of raw materials used in the formulation.
9. Date, time and duration of mixing.
10. Details of environmental controls like temperature, humidity, microbial count in the sterile working areas.
11. pH of the solution, wherever applicable.
11. Date and method of filtration.
12. Sterility test, release on bulk batch wherever applicable.
13. Record of check on volume filled.
14. Date of filling.
15. Records of test employed: - a) To ensure that sealed ampoules are leak proof b) To check the presence of foreign particles. c) Pyrogen test, wherever applicable. d) Toxicity test wherever applicable.
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16. Records of checking of instruments and apparatus of sterilization (indicators).
17. Records of cleaning and sterilization of containers and closures, if necessary.
18. Records of sterilization in case of parenteral preparations which are heat sterilized including particulars or time, temperature and pressure employed. Such records should be marked to relate to the batch sterilized.
19. Number and size of containers filled and quantity rejected.
20. The theoretical yield and actual yield and the percentage yield thereof.
21. Reference to Analytical report numbers stating whether of standard quality or otherwise.
23. Specimen of labels, cartons, etc. with Batch coding information like batch number, date of manufacture, date of expiry, as applicable, stamped thereon, and inserts used in the finished packings.
24. Signature with date of the component technical stall responsible for manufacture.
25. Particulars regarding the precautions taken during the manufacture to ensure that aseptic conditions are maintained.
26. Countersignature of head of the testing unit or person in charge of testing for having verified the documents and for having released the product for sale and distribution, the quantity released and date of release.
27. Records for having transferred to warehouse giving packings and quantities.
28. Separate records of the disposal of the rejected batches and of all batches withdrawn from the market.
29. Records of reprocessing if any and particulars of reprocessing.
II. RECORDS OF RAW MATERIALS
Records in respect of each raw material shall be maintained indicating the date of receipt, invoice number, name and address of the manufacturer/supplier, batch number, quantity received, pack size, date of manufacture, date of expiry, if any, date of analysis and release/rejection by quantity control, analytical report number, with special remarks, if any, quantity issued, date of
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issue and the particulars of the name and batch numbers of products for the manufacture of which issued and the proper disposal of the stocks.
III. PARTICULARS TO BE RECORDED IN THE ANALYTICAL RECORDS.
A. TABLETS AND CAPSULES.
1. Analytical report number. 2. Name of the sample 3. Date of receipt of sample 4. Batch/Lot number 5. Protocols of tests applied.
a) Description b) Identification c) Uniformity of weight d) Uniformity of diameter (if applicable). e) Disintegration test (time in minutes) f) Any other tests g) Results of Assay.
Note: - Records regarding various test applied (including readings and calculations) should be maintained and necessary reference to these records should be entered in Col. 5 above whenever necessary.
6. Signature of the Analyst. 7. Opinion and signature of the approved Analyst.
B. PARENTERAL PREPARATIONS.
1, Analytical report number. 2. Name of the sample 3. Batch number 4. Date of receipt of samples. 5. Number of containers filled. 6. Number of containers received. 7. Protocols of tests applied.
a) Clarity b) PH wherever applicable c) Identification. d) Volume in container. e) Sterility – (i) Bulk sample wherever applicable (ii) container sample. f) Pyrogen test, wherever applicable g) Toxicity test, wherever applicable
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h) Any other tests i) Results of Assay
Note: - Records regarding various test applied (including readings and calculations) should be maintained and necessary reference to these records should be entered in Col. 7 above, wherever necessary.
8. Signature of the Analyst. 9. Opinion and signature of the approved Analyst.
Pyrogen Test:
1. Test Report Number. 2. Name of the sample. 3. Batch Number. 4. Number of rabbits used. 5. Weight of each rabbit. 6. Normal temperature of each rabbit. 7. Mean initial temperature of each rabbit. 8. Dose and volume of solution injected into each rabbit and time of injection. 9. Temperature or each rabbit noted at suitable intervals. 10. Maximum temperature. 11. Response. 12. Summed response. 13. Signature of the Analyst. 14.Opinion and signature of the approved Analyst.
Toxicity Test
1. Test Report Number. 2. Name of the sample. 3. Batch Number. 4. Number of mice used and weight of each mouse. 5. Strength and volume of the Drugs injected. 6. Date of injection. 7. Results and remarks. 8. Signature of Analyst. 9. Opinion and signature of the approved Analyst.
C. FOR OTHER DRUGS 1. Analytical report number. 2. Name of the sample. 3. Batch/Lot number. 4. Date of receipt of sample.
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5. Protocol of tests applied. (a) Description. (b) Identification. (c) Any other tests. (d) Results of Assay.
Note :- Particulars regarding various tests applied (including readings and calculations) shall be maintained and necessary reference to these records shall be entered in Column 5 above, wherever necessary.
6. Signature of Analyst. 7. Opinion and signature of the approved Analyst.
D. RAW MATERIALS 1. Serial number, 2. Name of the materials. 3. Name of the manufacturer/supplier. 4. Quantity received. 5. Invoice/Challan number and date. 6. Protocols of test s applied.
Note: - Particulars regarding various tests applied (including readings and calculations) shall be maintained and necessary reference to these records shall be entered in Column 6 above, wherever necessary.
E. CONTAINER, PACKING MATERIALS ETC. 1. Serial number. 2. Name of the item. 3. Name of the manufacturer/supplier. 4. Quantity received. 5. Invoice/Challan number and date 6. Results of tests applied.
Note:- Particularsregarding various tests applied shall be maintained and necessary reference to these records shall be entered in column 6 above.
7. Remarks. 8. signature of the examiner.
Note: - The foregoing provisions represent the minimum requirements to be complied with by the licensee. The Licensing Authority, may however, direct the nature of records to be maintained by the licensee for such products as are not covered by the categories described above.
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2. The Licensing Authority may permit the licensee to maintain records in such manner as are considered satisfactory, provided the basic requirements laid down above are complied with.
3. The Licensing Authority may at its discretion direct the licensee to maintain records for such additional particulars as it may consider necessary in the circumstances of a particular case.]
1SCHEDULE U (I)
(See rules 142 and 142-B)
I. Particulars to be shown in the manufacturing Records: -
1. Serial number.
2. Name of the product.
3. Lot/Batch size.
4. Lot/Batch number
5. Date of commencement of manufacture and date when manufacture wascompleted.
6. Names of all ingredients, quantities required for the lot/batch size, quantities
actually used.
7. Control reference numbers in respect of raw materials used in formulation.
8. Reference to analytical report number.
9. Actual production and packing particulars indicating the size and quantity of
finished packings.
10. Date of release finished packing for distribution sale.
11. Signature of the expert staff responsible for the manufacture.
II. Records of Raw Materials-
Records in respect of each raw material shall be maintained indicating the quantity received, control reference number, the quantity issued from time to time, the names and batch numbers of the products for the manufacture of which the said quantity of raw material has been issued and the particulars relating to the proper disposal of the stocks.
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NOTE 1:The Licensing Authority may permit the licensee to maintain records in such manner as is considered satisfactory, provided the basic requirements laid down above are complied with.
NOTE 2:The Licensing Authority may direct the licensee to maintain records for such additional particulars, as it may consider necessary in the circumstances of a particular case.
_______________________________________________________________________________ 1Added by G.S.R. 1594, dated 13-11-1976, Govt. of India Notification No. X. 11014/4/76-&MS, dated 28-10-1976.
593 –A
Vitamin Unit Patent or proprietary Patent or proprietary Patent or proprietary medicines containing Medicines containing medicines containing vitamins for paediatric use. Vitamins for prophylactic vitamins for therapeutic Use.
___________________________________________________________________________________________________________________ in single dose or in two divided doses.
___________________________________________ per daily dose
For adults For infants less than For children above one one year. year upto adults
1 2 3 4 5 6
Vitamin A. I.U Not less than 1600 and not more than 2500
Not less than 5000 and not more than 10000
Not less than 750 and not more than 3000
Not less than 1500 and more than 5000
Vitamin D. I.U Not less than 100 and not more than 200.
Not less than 400 and not more than 1000
Not less than 200 and not more than 400
Not less than 100 and more than 400
Vitamin B1 mg. Not less than 1 and not more than 2
Not less than 4.5 and not more than 10
Not less than 0.5 and more than 1
Not less than 1 and not more than 4.5
Vitamin B2 mg Not less than 1 and not more than 3
Not less than 5 and not more than 10
Not less than 0.5 and not more than 1.5
Not less than 1 and not more than 5.
Vitamin B6 mg Not less than 0.5 and not more than 1.5
Not less than 1.5 and not more than 3
Not less than 0.5 and not more than 1.5
Not less than 1 and not more than 3
Niacinamide mg Not less than 15 and not more than 26
Not less than 45 and not more than 100
Not less than 5 and not more than 15
Not less than 10 and not more than 40.
d-Pantothenic acid or its salts and panthenol.
Mg Not less than 1 and not more than 5
Not less than 5 and not more than 50
Not less than 1 and not more than 3
Not less than 2.5 and not more than 10
593 – B
1 2 3 4 5 6
Folic acid mcg. Not less than 50 and not more than 300
Not less than 1000 and not more than 1500
Not less than 25 and not more than 100
Not less than 100 and not more than 500
Vitamin B12 mcg Not less than 0.5 and not more than 1
Not less than 5 and not more than 15
Not less than 1 and not more than 3
Not less than 1 and not more than 5
Vitamin C mg Not less than 25 and not more than 50
Not less than 75 and not more than 150
Not less than 20 and not more than 40
Not less than 30 and not more than 80
Vitamin E I.U Not less than 5 and not more than 10
Not less than 15 and not more than 25
Not less than 2.5 and not more than 10
Not less than 5 and not more than 20.
Note 1: Patent or proprietary medicines containing vitamins intended for prophylactic, therapeutic or paediatric use shall bear on the label the words “For Prophylactic Use” “ For Therapeutic Use,” or “For Paediatric Use” as the case may be. In the case of paediatric preparations the age of the infant or the child for whose use it is intended, shall be given in addition to the particulars required to be given under these rules.
Note 2: The above standards shall not apply to any preparation containing a single vitamin only and also to any preparation containing vitamins intended for parenteral use. Provided, however, that in the case of patent or proprietary medicines containing vitamins which are intended for the treatment of certain specific conditions or diseases, the Licensing Authority specified in clause (b) of rule 21, may permit the addition of vitamins therein in relaxation of the limits specified above, if satisfactory evidence is produced in justification of such relaxation.
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1SCHEDULE V
[ See rule 124-B]
Standards for patent or proprietary medicines.
1. 2[ * * * ]
32. Standards for patent or proprietary medicines, containing vitamins:
Patent or proprietary medicines containing vitamins for prophylactic, therapeutic or paediatric use shall contain the vitamins in quantities not less than and not more than those specified below in single or in two divided daily doses, namely: -
(See Table ) 43 5[* * *]
6[4. General Standards for Different Categories of Patent or Proprietary Medicines. -
In the case of Pharmaceutical products containing several active ingredients, the selection shall be such that the ingredients do not interact with one another and do not affect the safety and therapeutic efficacy of the product. The combination shall not also lead to analytical difficulties for the purpose of assaying the content of such ingredient separately. The substances added as additives shall be innocuous, shall not affect the safety or therapeutic efficacy of the active ingredients, and shall not affect the assays and identity tests in the amount present.
Subject to the provisions of these rules, patent or proprietary medicines shall comply with the following standards, namely: -
1. Patent or proprietary medicines shall comply with the general requirements of the dosage from under which it falls as given in the Indian Pharmacopoeia. If the dosage form is not included in the Indian Pharmacopoeia, but is included in any other pharmacopoeia, prescribed for the purpose of the Second Schedule to the Act, it shall comply with the general requirements ____________________________________________________________________________ 1 Added under G.S.R. No. 665, dated 28-5-1977 (Govt. of India Notification No. X. 11014/2/77-D & MS, dated 6-5- 1977). 2 Omitted as per G.O.I. Notification No. GSR 59(E) dt 22.1.1992., 3 Added under G.S.R. No. 930, published in the Gazette of India, Pt. II, Sec. 3, Sub-Sc. (i), dtd 22-7-1978. (G.O.I. Notification No. X. 11013/2/77-DMS & PFA dated 13th July, 1978.)
4and 5 Paragraph 3 inserted by G.O.I. Notification No. GSR 331(E) dt 8.5.1984 and omitted as per G.O.I. Notification No. GSR 59(E) dt 22.1.1992. 6 Inserted as per G.O.I. Notification No. GSR 792(E) dt 17.9.1987.
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of the dosage of such pharmacopoeia. Without prejudice to the generality of the foregoing requirements, general requirements shall include compliance with colour consistency, clarity, stability, freedom from contamination with foreign matter or fungal growth, defects like chipping and capping of tablets, cracking of the coating, mottled appearance and other characteristic defects that can be perceived by visual inspection.
2. Without prejudice to the generality of the following paras, dosage forms of patent or proprietary medicines shall comply with the following requirements, namely:-
a) Tablets: Medicines shall comply with requirements for tablets as laid down in the Indian Pharmacopoeia. The nature of coating shall be indicated on the label. Permitted colours may, however, be added and declared on the label. Nature of tablets, such as uncoated, sugar coated or film coated, shall be declared on the label.
b) Capsules : Medicines shall comply with the requirements for capsules laid down in the Indian Pharmacopoeia. However, the capsules shall be free from distortion or shape, dis- colouration and other physical defects like leakage of power from joints, pinholes or cracks in the capsules;
c) Liquid oral dosage forms: Emulsions and suspensions shall disperse uniformly on shaking. Homogeneous solutions shall contain no sediments. The volume of the product (net content) in the container shall be not less than the labeled volume. The limit for ethanol content of pharmaceutical products shall be not less than 90 per cent and not more than 110 per cent of the labeled contents.
d) Injections: Medicines shall comply with the requirements for injections as laid down in the Indian Pharmacopoeia.
e) Ointments: Medicines shall comply with the requirements for injections as laid down in the Indian Pharmacopoeia.
3. The contents of active ingredients, other than vitamins, enzymes and antibiotics, in patent or proprietary medicines shall be not less than 90 per cent and not more than 110 per cent of the labeled content; however, for enzymes and vitamins, only for lower limit of 90 per cent shall apply. In all dry formulations containing antibiotics, the limit shall be 90 to 130 per cent of the labeled contents and in case of liquid antibiotic formulations, the limit shall be 90 to 140 per cent of labeled contents.
Fiducial limits for error for microbiological assay of antibiotics may be estimated depending upon the design of assay procedure. Methods, used for assaying active ingredients shall employ the same basic principles and shall use same organisms as given in the latest edition of the Indian Pharmacopoeia or shall follow any other methods as approved by the authority competent to grant licence to manufacture.
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4. All patent or proprietary medicines containing aspirin shall be subjected to “Free Salicylic Acid Test” and the limit of such acid shall be 0.75 per cent. Except in case of soluble type aspirin in which case the limit of such acid shall be 3 per cent.
5. Patent or proprietary medicine to be tested under the provisions of Rule 121-A for pyrogen shall be tested by injecting into rabbits not less than the human dose of the medicine based on body weight of a 60 kg. human being. Methodology selected shall be indicated in the protocol but the dose shall be not greater than 5 times the human dose based on body weight of 60 kg for man.
6.In injectable patent or proprietary medicines, the test for freedom from toxicity, shall be performed as described in the Indian Pharmacopoeia. Dose selected shall be indicated in the protocol but the dose shall not be less than five times the human dose based on body weight of 60 kg. human being.]
SCHEDULE W (Schedule W) – Inserted as per G.O.I. Notificiation No. GSR 27(E) dt 17.1.1981 and deleted as per G.O.I. Notification No. GSR 94(E) dt 8.2.2000.
1[SCHEDULE X
[See Rules 23, 61, 75, 97 and 105.A]
Amobarbital 2[ Omitted] Amphetamina Methylphenidate Barbital Methylphenobarbital Cyclobarbital Pentobarbital Dexamphetamine Phencyclidine Ethclorvynol Phenmetrazine Glutethimide 3[Omitted} Meprobamate Secobarbital Methamphetamine
Note:- 1. Any stereoisometric form of the substance specified in this Schedule, any salt of the substance and preparation containing such substances are also covered by this Schedule.
____________________________________________________________________________ 1 Ins as per G.O.I. Notification No. GSR 462(E) dt 22.6.1982. 2 Omitted as per G.O.I. Notification No. GSR 647(E) dt 28.10.1998. 3 Omitted as per G.O.I. Notification No. GSR 673(E) dt 27.10.1993.
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2. Preparations containing the above substances are also covered by this Schedule.
Provided, however, preparations containing Meprobamate [* * *] 1 in combination with other drugs may be exempted by the Licensing Authority specified in clause (b) of Rube 21, from the provisions of this Schedule, if satisfactory evidence is adduced that these preparations are not liable to be misused.]
2[SCHEDULE Y REQUIREMENT AND GUIDELINES ON CLINICAL TRIALS FOR IMPORT AND
MANUFACTURE OF NEW DRUG.
1. Clinical Trials.
1.1.Nature of trials. - The clinical trials required to be carried out in the country before a new drug is approved for marketing depend on the status of the drug in other countries. If the drug is already approved/marketed, Phase III trials as required under Item 7 of Appendix 1 usually are required. If the drug is not approved/marketed trials are generally allowed to be initiated at one phase earlier to the phase of trials in other countries.
For new drug substances discovered in other countries phase I trials are not usually allowed to be initiated in India unless Phase I data as required under Item 5 of the said Appendix from other countries are available. However, such trials may be permitted even in the absence of Phase I data from other countries if the drug is of special relevance to the health problem of India.
For new drug substances discovered in India, clinical trials are required to be carried out in India right from phase I as required under Item 5 of the said Appendix though Phase III as required under Item 7 of the said Appendix, permission to carry out these trials is generally given in stages, considering the data emerging from earlier phase.
1.2.Permission for trials. - Permission to initiate clinical trials with a new drug may be obtained by applying in Form 12 for a test licence (TL) to import or manufacture the drug under the Rules. Data appropriate for the various phases of clinical trials to be carried out should accompany the application as per format given in Appendix I (items 1-4). In addition, the protocol for proposed trials, case report forms to be used, and the names of investigators and institutions should also be submitted for approval. The investigators selected should possess appropriate qualifications and experience and should have such investigations facilities as are germane to the proposed trials protocol.
Permission to carry out clinical trials with a new drug is issued along with a test licence in Form 11. ____________________________________________________________________ 1 Omitted as per G.O.I. Notification No. GSR 673(E) dt 27.10.1993. 2. Ins. by G.O.I. Notification No. GSR 944(E) dt 21.9.1998.
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It is desirable that protocols for clinical trials be reviewed and approved by the institution’s ethical committee. Since such committees at present do not exist in all institutions, the approval granted to a protocol by the ethical committee of one institution will be applicable to use of that protocol in other institutions which do not have an ethical committee. In case none of the trial centers/institutions has an ethical committee, the acceptance of the protocol by the investigator and its approval by the Drugs Controller (India) or any officer as authorized by him to do so will be adequate to initiate the trials.
For new drugs having potential for use in children, permission for clinical trials in the paediatric age group is normally given after phase III trials as required under item 7 of the said Appendix in adults are completed. However, if the drug is of value primarily in a disease of children, early trials in the paediatric age group may be allowed.
1.3.Responsibilities of Sponsor/Investigator. - Sponsors are required to submit to the licensing authority as given under Rule 21 an annual status report on each clinical trial, namely, ongoing, completed, or terminated. In case a trial is terminated, reason for this should be stated. Any unusual, unexpected or serious adverse drug reaction (ADR) detected during a trial should be promptly communicated by the sponsor to the licensing authority under Rule 21 and the other investigators.
In all trials an informal, written consent required to be obtained from each volunteer/patient in the prescribed Forms (See Appendix V) which must be signed by the patient/volunteer and the chief investigator.
2.Chemical and pharmaceutical information.
Most of the data under the heading (See Appendix I, item 2) are required with the application for marketing permission. When the application is for clinical trials only, information covered in item 2.1 to 2.3 of Appendix I will usually suffice.
3. Animal Toxicology.
3.1.Acute Toxicology. - Acute toxicity studies (See Appendix I item 4.2) should be carried out in at least two species usually mice and rats using the same route as intended for humans. In addition, at least one more route should be used to ensure systemic absorption of the drug; this route may depend on the nature of the drug. Mortality should be looked for up to 72 hours after parenteral administration and up to 7 days after oral administration. Symptoms, signs and mode of death should be reported, with appropriate macroscopic and microscopic findings where necessary. LD 50s should be reported preferably with 95 per cent confidence limited, if LD 50s cannot be determined, reasons for this should be stated.
3.2 Long term toxicity: - Long term toxicity (see appendix 1, item 1.3) should be carried out in at least tow mammalian species, of which one should be a non rodent. The duration of study
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will depend on whether the application is for marketing permission or for clinical trial, and in the latter case, on the phase of trials (see Appendix III). If a species is known to metabolize the drug in the same way as humans, it should be preferred.
In long-term toxicity studies the drug should be administered 7 days a week by the route intended for clinical use in humans. The number of animals required for these studies, i.e. the minimum number on which data should be available, is shown in Appendix IV.
A control group of animals given the vehicle along should always be included and three other groups should be given graded dose of the drug; the highest dose should produce observable toxicity, the lowest dose should not cause observable toxicity, but should be comparable to the intended therapeutic dose in humans of a multiple of it, e.g. 2.5 to make allowance for the sensitivity of the species; the intermediate dose should cause some symptoms, but not gross toxicity or death, and may be placed logarithmically between the other two doses.
The variables to be monitored and recorded in long-term toxicity studies should include behavioral, physiological, biochemical, and microscopic observations.
3.3.Reproduction studies. - Reproduction studies (see Appendix I, item 4.4) need to be carried out only if the new drug is proposed to be studied or used in women or childbearing age. Two species should generally be used, one of them being a non-rodent if possible.
a.Fertility Studies. - The drug should be administered to both males and females, beginning a sufficient number of days before mating. In females the medication should be continued after mating and the pregnant one should be treated throughout pregnancy. The highest dose used should not affect general health or growth of the animals. The route of administration should be the same as for therapeutic use in humans. The control and the treated group should be similar size and large enough to give at least 20 pregnant animals in the control group of rodents and at least 8 pregnant animals in the control group of non-rodents. Observations should include total examination of the litters from both the groups, including spontaneous abortions, if any.
b.Teratogenicity studies. - The drug should be administered throughout the period of organogenesis, using three dose levels. One of the doses should cause minimum maternal toxicity and one should be proposed dose for clinical use in humans or a multiple of it. The route of administration should be the same as for human therapeutic use. The control and the treated group should consist of at least 20 pregnant females in case of non-rodents, on each dose used. Observations should include the number of implantation sites; resorptions if any; and the number of foetuses with their sexes, weights and malformations, if any.
c.Perinatal studies. - The drug should be administered throughout the last third of pregnancy and then through lactation of weaning. The control of each treated group should have at least 12 pregnant females and the dose which causes low foetal loss should be continued
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throughout lactation weaning. Animals should be sacrificed and observations should include macroscopic autopsy and where necessary, histopathology.
3.4.Local toxicity. - These studies (see Appendix I, item 4.5) are required when the new drug is proposed to be used topically in humans. The drug should be applied to an appropriate site to determine local effects in a suitable species such as guinea pigs or rabbits, if the drug is absorbed from the site of applications, appropriate systemic toxicity studies will be required.
3.5Mutagenicity and Carcinogenicity. - These studies (see Appendix 1, item 4.5) are required to be carried out if the drug or its metabolite is related to a known carcinogen or when the nature and action of the drug is such as to suggest a carcinogenic/mutagenic potential. For carcinogenicity studies, at least two species should be used. These species should not have a high incidence of spontaneous tumors and should preferably be known to metabolize the drug in the same manner as humans. At least three dose level should be used; the highest dose should be sublethal out cause observable toxicity; the lowest dose should be comparable to the intended human therapeutic dose or a multiple of it, e.g. 2.5 X; to make intermediate dose to be placed logarithmically between the other two doses. A control group should always be included. The drug should be administered 7 days a week or a fraction of the life span comparable to the fraction of human life span over which the drug is likely to be used therapeutically. Observations should include macroscopic changes observed at autopsy and detailed histopathology.
4. Animal pharmacology.
Specific pharmacological actions (see Appendix I, item 3.2) are those with therapeutic- potential for humans. These should be described according to the animal models and species used. Wherever possible, dose-response relationships and ED 50s should be given. Special studies to elucidate mode of action may also be described.
General pharmacological action (see Appendix I, item 3.3) are effects on other organs and systems, specially cardiovascular, respiratory and central nervous systems.
Pharmacokinetic data help relate drug effect to plasma concentration and should be given to the extent available.
5 Human/Clinical Pharmacology (Phase I).
The objective of phase I of trials (see Appendix I, item 5) is to determine the maximum tolerated dose in humans; pharmacodynamic effects; adverse reactions, if any, with their nature and intensity; and pharmacokinetic behaviour of the drug as far as possible. These studies are carried out in healthy adult males, using clinical, physiological and biochemical observations. At least 2 subjects should be used on each dose.
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Phase I trials are usually carried out by investigators trained in clinical pharmacology and having the necessary facilities to closely observe and monitor the subjects. These may be carried out at one or two centers.
6. Explanatory trials (Phase II).
In phase II trial (see appendix I, item 6) a limited number of patients are studies carefully to determine possible therapeutic use, effective dose range and further evaluation of safety and pharmacokinetics. Normally 10-12 patients should be studied at each dose level. These studies are usually limited to 3-4 centres and carried out by clinicians specialized in the concerned therapeutic areas and having adequate facilities to perform the necessary investigations for efficacy and safety.
7. Confirmatory trials (Phase III).
The purpose of these trials (see Appendix I, item 7) is to obtain sufficient evidence about the efficacy and safety of the drug in a larger number of patients, generally in comparison with a standard drug and/or a placebo as appropriate. These trials may be carried out by clinicians in the concerned therapeutic areas, having facilities appropriate to the protocol. If the drug is already approved/marketed in other countries, phase III data should generally obtained on at least 100 patients distributed over 3-4 centres primarily to confirm the efficacy and safety of the drug, in Indian patients when used as recommended in the product monograph for the claims made.
If the drug is a new drug substance discovered in India and not marketed in any other country, phase III data should be obtained at least 500 patients distributed over 10-15 centres. In addition, data on adverse drug reactions observed during clinical use of the drug should be collected in 1000-2000 patients; such data may be collected through clinicians who give written consent to use the drug as recommended and to provide a report on its efficacy and adverse during reactions in the treated patients. The selection of clinicians for such monitoring and supply of drug to them will need approval of the licensing authority under Rule 21.
8. Special Studies.
A. These include studies on solid oral dosage form, such as, bio-availability and dissolution studies. These are required to be submitted on the formulations manufactured in the country. (see Appendix I, items 8.2 and 8.3).
B. These include studies to explore additional aspects of the drug, e.g. use in elderly patients or patients with renal failure, secondary or ancillary effects, interactions, etc. (See Appendix 8.2 and 8.3).
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9. Submission of Reports (Appendix II).
The reports of completed clinical trials shall be submitted by the applicant duly signed by the investigator with a stipulated period of time. The applicant should do so even if he is no longer interested to market the drug in the country unless there are sufficient reasons for not doing so.
10. Regulatory status in other countries.
It is important to state if any restrictions have been placed on the use of the drug in any other country, e.g. dosage limited, exclusion of certain age groups, warnings about adverse drug reaction, etc. (See Appendix I, item 9.2).
Likewise, if the drug has been withdrawn from any country specially by a regulatory directive, such information should be furnished along with reasons and their relevance, if any, to India (See appendix I, item 9.1 (d).
11. Marketing information.
The product monograph should comprise the full prescribing information necessary to enable a physician to use the drug properly. It should include description, actions, indications, dosage precaution, drug interactions, warnings and adverse reactions.
The drafts of label and carton texts should comply with provisions of Rules 96 and 97 of the said rules.
*[12 Post-marketing surveillance study.
On approval of a new drug, the importer or the manufacturer shall conduct post-marketing surveillance study of that new drug after getting the protocols and the names of the investigators approved by the Licensing Authority as defined under clause (b) of Rule 21 during the initial period of two years of marketing.]
__________________________________________________________________________ * Ins. by G.O.I. Notification No. 900(E) dt 12.12.2001.
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APPENDIX I
Data required to be submitted with application for permission to market a New Drug
1. INTRODUCTION
A brief description of the drug and the therapeutic class to which it belongs.
2. CHEMICAL AND PHARMACEUTICAL INFORMATION.
2.1. Chemical name, code name or number, if any, non-proprietary or generic name, if any, structure, physio-chemical proportion.
2.2 Dosage form and its composition. 2.3 Specifications of active and inactive ingredients. 2.4. Tests for identification of the active ingredient and method of its assay. 2.5. Outline of the method of manufacture of the active ingredient.
2.6 Stability data
3. ANIMAL PHARMACOLOGY
3.1. Summary
3.2. Specific pharmacological actions.
3.3 General pharmacological actions.
3.4. Pharmacokinetics, absorption, distribution, metabolism, excretion.
4. ANIMAL TOXICOLOGY (See Appendix III and IV) 4.1. Summary 4.2 Acute Toxicity 4.3. Long Term Toxicity 4.4 Reproduction Studies. 4.5 Local Toxicity 4.6. Mutagenicity and Carnicogenicity.
5. HUMAN/CLINICAL PHARMACOLOGY (PHASE I).
5.1. Summary 5.2 Specific Pharmacological effects. 5.3 General Pharmacological effects. 5.4. Pharmacokinetics, absorption, distribution, metabolism, excretion.
6. EXPLANATORY CLINICAL TRIALS (PHASE II).
6.1. Summary
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6.2 Investigatorwise reports. 7.. CONFIRMATORY CLINICAL TRIALS (PHASE III)
7.1. Summary 7.2 Investigatorwise reports
8. SPECIAL STUDIES
8.1. Summary 8.2 Bioavailability and dissolution studies. 8.3 Investigatorwise reports.
9. REGULATORY STATUS IN OTHER COUNTRIES.
9.1. Countries where –
(a) Marketed (b) Approved. (c) Under trial, with phase. (d) Withdrawn, if any, with reasons.
9.2. Restrictions on use, if any, in countries where marketed/approved. 9.3 Free sale certificate from country of origin.
10.MARKETING INFORMATION.
10.1. Proposed product monograph 10.2. Drafts of labels and cartons. 10.3. Sample of pure drug substance, with testing protocol.
Notes: (1) All items may not be applicable to all drugs, for explanation, see text of Schedule Y.
(2) For requirements of data to be submitted with application for clinical trials see text of Schedule Y, Section 1 and also Appendices II and III.
*[APPENDIX 1-A [See Rules 122-A and 122-B)
Data required to be submitted by an applicant for grant of permission to import manufacture an already approved new drug.
1. INTRODUCTION
A brief description of the drug and the therapeutic class. ___________________________________________________________________________ * Ins. by G.O.I. Notification No. GSR 900(E) dt 12.12.2001.
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2. CHEMICAL AND PHARMACEUTICAL INFORMATION.
2.1. Chemical name, code name or number, if any, non-proprietary or generic name, if any, structure, physico-chemical properties.
2.2. Dosage from its composition
2.3. Test specifications. (a) active ingredients. (b) Inactive ingredients
2.4. Tests for identification of the active ingredients and method of its assay. 2.5. Outline of the method of manufacture of active ingredients. 2.6. Stability data.
3. Marketing information.
3.1 Proposed package insert/promotional literature 3.2 Draft specimen of the label and carton.
4. Special studies conducted with approval of Licensing Authority.
4.1. Bioavailability/Bioequivalance and comparative Dissolution Studies, for oral dosage form,
4.2. Sub-acute animal toxicity studies for intravenous infusions and injectables.]
APPENDIX II
Format for submission of clinical Trial Reports.
___ Title of the trial
___ Name of investigator and institution
___ Objectives of the trial
___ Design of study: Open, single-blind or double blind, non-comparative or comparative, parallel group or crossover.
___ Number of patients, with criteria selection and exclusion, whether written, informed consent, was obtained.
___ Treatments given – drugs and dosage forms, dosage regimens, method of allocation of patients to treatments, method of verifying compliance, if any
___ Observations made before, during and at the end of treatment, for efficacy and safety, with methods used.
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___ Results : exclusions and dropouts, if any, with reasons, description of patients with initial comparability of groups where appropriate, clinical patients with initial comparability of groups where appropriate, clinical and laboratory observations on efficacy and safety, adverse drug reactions.
___ Discussion of results ; relevance to objectives, correlation with other reports/data, if any, guidance for further study, if necessary.
___ Summary and conclusion.
APPENDIX III
Animal toxicity requirements for clinical trials and marketing of a New Drug.
Route of administration Duration of Human administration
Phase Long term toxicity requirements.
1 2 3 4
Single dose of several doses in one day.
I-III MP 2 sp; 2 wk
I, II 2 sp ; Up to 4 wk
III MP 2 sp; Up to 3 mo
Up to 2 wk
I, II 2 sp; 4 wk
Up to 3 wk III 2 sp; 3 mo
MP 2 sp; Up to 6 mo
I, II 2 sp; 3 mo
Oral or Parenteral or Transdermal
Over 3 mo
III: MP 2 sp; 6 mo
Inhalation (general Anaesthetics)
I: III MP 4 sp; 5d(3h/d)
I; II 1-2 sp; 3h/exp.
III 1-2 sp; Up to 6 wk (2 exp/d)
Aerosole Repeated or Chronic use
MP 1-2 sp; 24 wk (2 exp/d)
Dermal Short term or long Term application
I: II 1 sp; single 24h exp; then 2 wk observation
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III: MP 1 sp. number and duration of applications commensurate with duration of use.
Ocular or Otic or Nasal Single or Multiple Applications.
I: II Irrigation test; Graded doses.
III 1 sp; 3 wk; dailyapplications as in clinical use.
MP 1 sp; number and or duration of application commensurate with duration of use.
Vaginal or Rectal Single or Multiple Application
I : II
III : MP
1 sp; number and duration of applications commensurate with duration of use.
Abbrevations : Sp-species, wk- week, d- day, h-hour, mo-month, MP-Marketing Permission, exp-exposure, I,II,III – Phases of clinical trial (see Appendix I, item No.5-8).
Note: - (1) Animal toxicity data available from other countries are acceptable and do not need to be repeated/duplicated in India.
(2) Requirements for fixed dose combinations are given in Appendix VI.
APPENDIX IV
Number of animals for long term Toxicity Studies.
2 - 6 Weeks 7 - 26 Weeks
Group Rodents (rats) Non-Rodents (dogs)
Rodents (Rats)
Non-Rodents (dogs)
M F M F M F M F Control 6 – 10 6 – 10 2 –3 2 –3 15 –30 15 –30 4—6 4—6
Low dose 6 – 10 6 – 10 2 –3 2 –3 15 –30 15 –30 4—6 4—6
Intermediate dose 6 – 10 6 – 10 2 –3 2 –3 15 –30 15 –30 4—6 4—6
High dose 6 – 10 6 – 10 2 –3 2 –3 15– 30 15 - 30 4—6 4—6
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APPENDIX V
Patient consent form for participation in a Phase I Clinical Trial
The clinical trial involves the study of a new …………. agent …………….. in volunteers/patients suffering from ……………………………………………………………….
The drug which will be administered to volunteers/patients has been found to be safe in animal toxicity tests and other experimental data. The volunteers /patients will be required to undergo, if necessary, all routine examinations including taking of X-ray, ECG, EEG etc. at intervals. The volunteers/patients may be asked to collect stool and urine, and there may be need to draw blood or any other body fluid on several occasions to test the effects of concentrations of the drug. The volunteers/patients are free to withdraw from the trial at any stage.
Authorisation
I have read/been briefed on the above project summary and I voluntarily agree to participate in the project. I understand that participation in this study may or may not benefit me. Its general purpose, potential benefits, possible hazards, and inconveniences have been explained to my satisfaction, I hereby give my consent for this treatment.
Name of the volunteer/patient
Signature or thump impression of the volunteer/patient.
Signature of Chief Investigator Date:
Patient consent form for participation in Phase II and Phase III Clinical Trial: -
I…………………………….. exercising my free power of choice, hereby give my consent to be included as a subject in the clinical trial of a new drug, namely……………….. for the treatment of …………………….. I understand that I may be treated with this drug for the diseases. I am suffering from ………………………I have been informed to my satisfaction, by the attending physician the purpose of the clinical trial and the nature of drug treatment and follow up including the laboratory investigation to monitor and safeguard my body functions.
I am also aware of my right to opt out of the trial at any time during the course of the trial without having to give the reasons for doing so.
Signature of the attending physician.
Date: …………. Signature of the patient Date:
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APPENDIX VI
Fixed Dose Combination (FDC) fall into four groups and their data requirements accordingly.
(a) The first group of FDC includes those in which one or more of the active ingredients is a new drug. Such FDC are treated in the same way as any other new, drug, both the clinical trials and for marketing permission (See Rule 122-E, item (a).)
(b) The second group of FDC includes those in which active ingredients already approved/marketed individually are combined for the first time, for a particular claim and where the ingredients are likely to have significant interaction of a pharmacodynamic or pharmacokinetic nature (see Rule 122-E, item (c)). For permission to carry out clinical trials with such FDC, a summary of available pharmacological, toxicological and clinical data on the individual ingredients should be submitted, with rationale for combining them in the proposed ratio. In addition, actual toxicity data (LD 50) and pharmacological data should be submitted on the individual ingredients as well as their combination in the proposed ratio. If the clinical trials have been carried out with the FDC in other countries, reports of such trials should be submitted. If the FDC is marketed abroad, the regulatory status in other countries should be stated. (See Appendix , item 9).
For marketing permission, the reports of clinical trails carried out with the FDS in India should be submitted. The nature of trials depending on the claims to be made and the data already available.
(c) The third group of FDC includes those which are already marketed, but in which it is proposed either to change the ratio of active ingredients or to make a new therapeutic claim.
For such FDC, the appropriate rationale should be submitted to obtain a permission for the clinical trials, and the reports of trials should be submitted to obtain a marketing permission. The nature of trails will depend on the claims to be made and the data already available.
(d) The fourth group of FDC includes those whose individual active ingredients have been widely used in particular indication for years, their concomitant use is often necessary and no claim is proposed to be made other than convenience, and a stable acceptable dosage from the ingredients are unlikely to have significant interaction of a pharmacodynamic or pharmacokinetic nature.
No additional animal or human data are generally required for these FDC, and marketing permission may be granted if the FDC has an acceptable rationale.
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NOTIFICATIONS ISSUED UNDER THE DRUGS AND COSMETICS ACT, 1940 _____________________
I.Notifications pertaining to prohibition of manufacture etc of drugs: - Notifications issued under Section 26 A of the Act: [ 1 Amidopyrin.
2 Fixed dose combinations of Vitamins with anti-inflammatory agents and tranquilisers
3 Fixed dose combinations of atropine inAnalgesics and anti-pyretics. 4 Fixed dose combinations of Strychnine and Caffeine in tonics. 5 Fixed dose combinations of Yohimbine and Strichnine with Testosterone and
Vitamins. 6 Fixed dose combinations of Iron with Strichnine, Arsenic and Yohimbine. 7 Fixed dose combinations of sodium Bromide/ chloral Hydrate with other drugs. 8 Phenacetin. 9 Fixed dose combinations of anti-histaminics with anti- diarrhoeals.
10 Fixed dose combinations of Penicillin with Sulphonamides. 11 Fixed dose combinations of Vitamins with Analgesics 12 Fixed dose combinations of Tetracycline with Vitamin C. 13 Fixed dose combinations of Hydroxyquinoline group of drugs except
preparations preparations meant for external use. [14 Fixed dose combinations of corticosteroids with any other drug for internal use. 15 Fixed dose combinations of Chloramphenicol with any other drug for internal
use.] 16 Fixed dose combinations of crude Ergot except those containing Ergotamine,
caffeine, analgesics, antihistamines for the treatment of Migraine headaches. 17 Fixed dose combinations of Fixed dose combinations ofitamins with
antiT.B.Drugs except combination of Isoniazid with Pyridoxin Hydrochloride ( Vitamin B6.)
18 Penicillin skin/eye ointment 19 Tetrracycline liquid oral preparations. 20 Nialamide. 21 Practolol. 22 Methapyrilene, its salts.] 23 Methaqulone. 24 Oxytetracycline Liquid Oral Preparations. 25 Democlocycline Liquid Oral Preparations. 26. Combinations of Anabolic steroids with other drugs.
611
27 Fixed dose combination of Oestrogen and Progestin(other than oral contraceptives) containing per tablet oestrogen content of more than50 mcg.(equivalent to Ethenyl Estradiol) and progestin content of more than 3 mg(equivalent to Norethysterone Aceate and all fixed dose combination injectable preparations containing synthetic oestrogen and progesterone.
28 Fixed dose combination of Sedatives/hypnotics/anxiolytics with analgesic – antipyretics.
29 Fixed dose combination of Pyrazinamide with other anti tubercular drugs except combination of Pyrazinamide with rifampicin and INH as per recommended daily dose given below: -
Minimum Maximum. Rifampicin 450 mg 600 mg INH 300 mg 300 mg Pyrazinamide 1000 mg 1500 mg.
30 Fixed dose combination of histamin H2 – receptor antagonists with antacids except those combinations approved by the Drugs Controller, India.
31 The patent and proprietary medicines of fixed dose combinations of essential oils with alcohol having a percentage higher than 20% proof except preparations given in the Indian Pharmacopoea.
32 All Pharmaceutical preparations containing Chloroform exceeding 0.5% w/w or whichever is appropriate.
33 Fixed dose combination of Ethambutol with INH other than the following: INH Ethambutol 200 mg 600 mg. 300 mg. 800 mg.
34 Fixed dose combination containing more than one antihistamine. 35 Fixed dose combination of anthelmintic with cathetric/ purgative except for
piperazine. 36 Fixed dose combination of salbutamol or any other bronchodialator with
centrally acting anti-tussive and/or antihistaminic. 37 Fixed dose combination of laxatives and/or anti-spasmodic drugs in enzyme
preparations. 38 Fixed dose combination of Metaclopromide with other drugs except for
preparations containing Metaclopromide and aspirin/ paracetamol. 39 Fixed dose combination of centrally acting anti-tussive with antihistamine
having high atropin like activity in expectorants. 40 Preparations claiming to combat cough associated with asthma containing
centrally acting anti-tussive and/or other antihistamine. 41 Liquid oral tonic preparations containing and/or otherphosphates and/or central
nervous system stimulant and such preparations containing alcohol more than 20% proof.
42 Fixed dose combination containing Pectin and/or Kaolin with any drug which is systemically absorbed from GI tract except for combinations of Pectin and/or
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Kaolin with drugs not systemically absorbed. 43 Chlora Hydrate as a drug. 44 Dover’s Powder I.P. 45 Dover’s Powder Tablets I.P. 46 Anti diarrhoeal formulations containing Kaolin or Pectin or Attapulgite or
activated charcoal. 47 Anti diarrhoeal formulations containing Phthalyl sulphathiazole or
Sulphaguanidine or Succinyl Sulphathiazole. 48 Anti diarrhoeal formulations Neomycin or Streptomycin or Dihydrostreptomycin
including their respective salts and esters. 49 Liquid oral anti-diarrhoeals or any other dosage form for paediatric use
containing Diphenoxylate or Loparamide or Atropine or Belladonna including their salts or esters or metabolites Hyoscyamine or their extracts or their alkaloids.
50 Liquid oral anti-diarrhoeals or any other dosage form for paediatric use containing halogenated hydroxyquinolines.
51 Fixed dose combination or anti-diarrhoeals with electrolytes. 52 Patent and Proprietary Oral Rehydration Salts other than those conforming to the
following parameters: (a) Patent and Proprietary Oral Rehydration Salts on reconstitution to one
liter shall contain: - Sodium – 50 to 90 millimoles. Total osmolarity – not more than 290 millimoles. Dextrose:Sodium molar ratio- not less than 1:1 and not more than 3:1.
(b) Patent and Proprietary cereal based Oral Rehydration Salts on reconstitution to one liter shall contain: - Sodium – 50 to 90 millimoles. Total osmolarity – not more than 290 millimoles. Precooked rice - equivalent to not less than 50 gms. And not more than 80 gms. As total replcement of dextrose.
© Patent and Proprietary Oral Rehydration Salts (ORS) may contain aminoacids in addition to Oral Rehydration Salts conforming to the parameters specified above and labeled with the indication “ For Adult Choletric Diarrhoea only.”
(d) Patent and Proprietary Oral Rehydration Salts shall not containMono or Polysaccharides or saccharine sweetening agent.
53 Fixed dose combination of Oxyphenbutazone or Phenylbutazone with any other drug.
54 Fixed dose combination of Analgin with any other drug.[ The words ‘other than anti-spasmodics’ omitted by G.O.I. notification no.405(E) dt.03.06.1999.]
55 Fixed dose combination dextropropoxyphene with any other drug other than anti-spasmodics and/or non-steroidal anti-inflammatory drugs (NSAIDS).
56 Fixed dose combination of a drug, standards of which are specified in the Second
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Schedule to the said Act with an Ayurvedic, Siddha or Unani drug. 57 Mepacrine Hydrochloride (Quinacrine and its salts) in any dosage form for use
for female sterilization or contraception. 58 Fenfluramine and Dexfenfluramine. 59 Fixed dose combination of diazepam and diphenhydramine Hydrochloride.
Items 1 to 22 were prohibited as per G.O.I. Notification No. G.S.R.578(E) dt23.07.1983. and items 14 and 15 were subs. by G.O.I.Notification No.X.11014/2/88 DMS&PFA. G.S.R.1057(E) dt 03.11.1988. . Item No.13 was subs. By G.O.I.notification No.G.S.R.793(E) dt.13.12.1995.
. Item no. 23 was Ins. by G.O.I.notification No.G.S.R.49(E) dt.31.01.1994. . Items no.24 and 25 were Ins. by G.O.I.notification No.G.S.R.322(E)
dt.03.05.1984. Item no. 26 was Ins. by G.O.I.notification No.G.S.R.863(E) dt.22.11.1985. Item no. 27 was Ins. by G.O.I.notification No.G.S.R.700(E) dt.15.06.1988 and. was subs. by G.O.I.notification No.G.S.R.743(E) dt.10.08.1989.
. Items nos. 28 to 32 were Ins. by G.O.I.notification No.G.S.R.999(E) dt.26.12.1990.
Items nos. 33 to 42 were Ins. by G.O.I.notification No.G.S.R.69(E) dt.11.02.1991 and Item no. 38 was subs. by G.O.I.notification No.G.S.R.603(E) dt.24.08.2001.
Item no 43 was Ins. by G.O.I.notification No.G.S.R.304(E) dt.07.06.1991. Items nos. 44 and 45 were Ins. by G.O.I.notification No.G.S.R.111(E)
dt.22.02.1994 and corrected by G.S.R. No. 612(E) dt.09.08.1994. Items nos. 46 to 51 were Ins. by G.O.I.notification No.G.S.R.731(E)
dt.30.09.1994. Item no. 52 was Ins. by G.O.I.notification No.G.S.R.57(E) dt.07.02.1995. Items nos. 53 to 56 were Ins. by G.O.I.notification No.G.S.R.633(E)
dt.13.09.1995. Items nos. 57 and 58 were Ins. by G.O.I.notification No.G.S.R.499(E)
dt.14.08.1998. Items nos.59 and 60 which had been ins. by G.O.I.Notification No.590(E)
dt.17.08.19999 were deleted by G.O.I.Notification No.704(E) dt. 20.10.1999. The present item 59 was Ins. by G.O.I.notification No.G.S.R.169(E) dt.12.03.2001.
Other drugs prohibited without being made part of the list above: - (i) Fixed dose combination of Penicillin with Streptomycin- vide G.S.R. No.
93(E) dt.25.02.1997,w.e.f.01.01.1998.
(ii) Fixed dose combination of Vitamin B1,Vitamin B6 and Vitamin B12- vide G.S.R. No.702(E) dt.14.10.1999,w.e.f.01.01.2001.
(iii) 1. Fixed dose combination of haemoglobin in any form ( natural or synthetic.)
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2. Fixed dose combination of Pancreatin with Pancrelipase containing amylipase, protease and lipase wqith any other enzyme.
- vide G.O.I. Notification No. G.S.R.814(E) dt.16.12.1999 w.e.f.01.09.2000
(iv) 1. Fixed dose combination of Nitrofurantoin and trimethprim. 2. Fixed dose combination of Phenobarbitone with any anti-asthmatic drug. 3. Fixed dose combination of Phenobarbitone with Hyoscine and/or Hyoscyamine. 4. Fixed dose combination of Phenobarbitone with Ergotamine and or Belladonna. 5. Fixed dose combination of Haloperidol with any anti-cholinergic agent includingPropanthelene Bromide. 6. Fixed dose combination of Nalidixic acid with any anti-amoebics including Metronidazole. 7. Fixed dose combination of Loperamide Hydrochloride with Furazolidone. 8. Fixed dose combination of Cyproheptadine with Lysine or Peptone. -items 1 to 8 above prohibited vide G.O.I.Notification. No G.S.R.170(E) dt.12.03.2001, w.e.f. 01.01.2002.
COSMETIC prohibited under Sec.26.A of the Drugs and Cosmetics Act.1940: -
Tooth pastes/ tooth powders containing tobacco. -vide G.O.I. Notification No.G.S.R.444(E) dt.30.04.2002.
Drugs prohibited under section 33 Eed of the Drugs and Cosmetics Act,1940:-
All Ayurvedic drugs licensed as tooth pastes/ tooth powders containing tobacco. -vide G.O.I. Notification No.G.S.R.443(E) dt.30.04.2002.
II. Prohibition of Import under section 10-A of the Drugs and Cosmetics Act,1940.
1.G.O.I. Notification. No. G.S.R.577 (E) dt.23.07.1983.
1.Nialamide. 2.Practolol. 3.Amidopyrin. 4.Phenacetin. 5.Methapyrilene and its salts.
2. G.O.I. Notification. No. G.S.R.48 (E) dt.31.01.1984.. 6.Methaqualone.
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3. G.O.I. Notification. No. G.S.R.303 (E) dt.07.06.1991 7.Chloral Hydrate as a drug.
4. G.O.I. Notification. No. G.S.R.498 (E) dt.14.08.1998. 8.Mepacrine Hydrochloride (Quinacrine and its salts) in any dosage form for use
for female sterilization or contraception. 9.Fenfluramine and Dexfenfluramine.
NOTIFICATIONS AS DRUGS
1. G.O.I. Notification No.1-20/60-D dt.03.06.1961. 11. Contraceptives. 22. Disinfectants.
3(1) Disinfectant fluids made from Coaltar Oils, Coaltar acids or similar acids derived from petroleum with or without hydrocarbons.
(2) Disinfectant fluids from synthetic or naturally occurring substances other than those mentioned in (1) above by virtue of their composition possessing disinfectant properties or with claim to possess disinfectant properties.
2. G.O.I. Notification No G.S.R. 365(E) dt 17.03.1989. (i) Disposable Hypodermic Syringes. (ii) Disposable Hypodermic needles. (iii) Disposable Perfusion Sets. 4(iv) In-vitro diagnostic devices for HIV, HbsAg & HCV.
. (w.e.f.01.09.2002.)
.
1Amended by G.O.I. Notification No.F.1-20/60-D dt.29.9.1962. 2Amended by G.O.I. Notification No X.11013/2/72 dt.09.07.1975.
3Amended by G.O.I. Notification No. F1-49/68-D dt.11.06.1969. 4 Ins.by G.O.I.Notification No.G.S.R.601(E) dt.27.08.2002.