Technology Transfer and Voluntary Licensing to Address the Global Cholera Vaccine Shortage and Africa’s Vaccine Production Goals

April 27, 2023

Over the past year, demand for the Oral Cholera Vaccine (OCV) has exploded. As of March 2023, at least 24 countries continue to report cholera cases, according to the World Health Organization (WHO). Unfortunately, due to global challenges such as climate change, armed conflict and displacements, cholera outbreaks are expected to increase. The disease, which is caused by the bacterium Vibrio cholerae, is transmitted via contaminated food or water. Cholera can kill within hours if left untreated so it is essential to prevent and control its transmission. Ideally, cholera vaccination campaigns are complemented by improvements in water and sanitation as well as community sensitization programs to help ensure good hygiene practices, especially in areas vulnerable to outbreaks.

Background

The Global OCV Stockpile was established in 2013. It is managed by the International Coordinating Group (ICG) and supported by Gavi, the Vaccine Alliance, since 2014.  Since then, 73 million doses of OCV have been distributed in 23 countries. This is a good start, but lags behind the estimated demand, which is more than 75 million doses per year. The unprecedented number and severity of outbreaks in 2022, coupled with limited OCV supply, forced the ICG to temporarily suspend the standard two-dose vaccination regimen recommended in outbreak response campaigns in favor of a single-dose approach.

The first dose of OCV has proven to help control an outbreak even with limited evidence on the exact duration of the protection. The second dose, which is administrated within six months of the first, provides immunity for three years. We can therefore see that a temporary suspension of the two-dose regimen is only a short-term solution.  In the longer term, urgent measures are needed to increase global vaccine production.

The challenge

The supply landscape of cholera vaccines is extremely limited. Currently there are three WHO pre-qualified oral cholera vaccines.  Dukoral® manufactured by Valneva Sweden AB, Shanchol™ manufactured by Shantha Biotechnics (Indian subsidiary of Sanofi) and Euvichol-Plus® manufactured by EuBiologics Co. Ltd. Shanchol™ and Euvichol-Plus® are currently available through the Global OCV Stockpile. In 2022, Shantha Biotechnics, which produces about 15% of the world's supply of OCV, announced that it would end production and distribution of Shanchol™ by 2023. Although EuBiologics Co. intends to increase its production capacity of Euvichol-Plus®, this will take time. The COVID-19 pandemic has also demonstrated the problems that can arise from single source or limited number of manufacturers and suppliers. New manufacturers with a greater geographical scope are thus urgently needed to meet the increasing demand for OCV.

A groundbreaking license and technology transfer agreement

The OCV market is not a lucrative one. These vaccines are inexpensive and require bulk sales to generate profit.  Voluntary intellectual property (IP) licensing and technology transfer may play a role in accelerating manufacturers' interest in producing and distributing oral cholera vaccines. Therefore, IP rights can be an enabler for access to health technologies. A key example is the licensing and technology transfer agreement between Biovac, a South African bio-pharmaceutical company, and the International Vaccine Institute (IVI), a non-profit international organization headquartered in South Korea, for the manufacture of OCV.

IVI developed the world’s first low cost WHO Pre-qualified oral cholera vaccine and entered into a technology transfer agreement with BioVac in November 2022. The agreement will build local capacity in Africa for the production of the antigen/raw material needed to manufacture actual vaccines. This transfer of technology will also establish local capacity for Good Manufacturing Process (GMP) scale-up, local manufacture of clinical trial products and end-to-end production of vaccines in Africa. The project is supported by a USD 6.9 million grant from Wellcome Trust and the Gates Foundation. The funding will enable  Biovac to expand its capabilities from filling and packaging of vaccine vials to end-to-end vaccine product development and drug substance manufacture. Biovac expects to manufacture the first batches of OCV ready for clinical trials in 2024. The regulatory authorization by the South African Health Products Regulatory Authority (SAHPRA), is expected to be completed in 2026.

This licensing and technology transfer agreement is important in many ways:

• It will enable the production of the actual drug substance needed to manufacture OCV, meaning that Biovac will be the first African vaccine manufacturer to achieve end-to-end vaccine product development of OCV.
• Expanding manufacturing capacity of OCV will significantly contribute to the ‘Ending Cholera—A Global Roadmap to 2030’ which aims to achieve a 90% reduction in cholera deaths and cholera elimination in 20 countries by the end of the current decade.
• If WHO pre-qualification is achieved, UN agencies such as WHO and UNICEF would be able to procure OCV from Biovac. Thus, Africa would significantly contribute towards meeting the global shortage of oral cholera vaccines.
• It will contribute to the goal set by the African Union to enable the African vaccine manufacturing industry to produce 60 % of all vaccine doses required on the continent by 2040. This is a bold goal given that they’re starting from less than 1% in 2021.

This is a significant step for vaccine production in Africa. But it’s just a start as more manufacturers in low and middle income countries (LMICs) are urgently needed. The Global Task Force on Cholera Control (GTFCC) modeling shows that population growth and urbanization could double the number of cholera cases over the next 20 years. Strengthening local capacity in LMICs to manufacture OCV through licensing and technology transfer needs therefore to happen systematically.

WIPO’s work in support of tech transfer and local production

IP can be a tool to support local production through licensing and technology transfer. WIPO remains committed to working with a wide range of stakeholders to positively leverage intellectual property as a tool towards equitable access to health products.

For example, WIPO’s forthcoming publications related to technology transfer in the life sciences sector,  include: Biotechnology Technology Transfer: A Primer; Socially Responsible IP Commercialization in Academic Institutions and IP Management and Technology Transfer in the field of Life Sciences.

In addition, the most recent episode of WIPO’s Mission Imagination series featured Dr. Patrick Tippoo, Chief Science and Innovation Officer at the Biovac Institute and the Executive Director of the African Vaccine Manufacturing Initiative (AVMI). During the interview, Dr. Tipoo addresses the Biovac licensing agreement and how it has brought relevant stakeholders together to begin operationalizing the continent’s vaccine manufacturing goals.