mRNA Vaccine Technology Transfer and Training Hub: DSI & stakeholder briefing

Meeting report

Chairperson Mkhatshwa said the Portfolio Committee on Health was invited for this joint briefing. Ideally the session should have been an onsite visit at the facilities in Cape Town but due to the unavailability of some Members, the visit will be rescheduled. It was important to have a joint meeting because government was not doing well in synergising its work. The purpose of the joint meeting was to close the gap that was stagnating the work of government and the Committees. The Portfolio Committee on Higher Education and Training had been discussing the work that was being done on the mRNA vaccine. It was important for South Africa to have its own capacity to develop and manufacture vaccines. The subject was not new to Members because the Department had been keeping the Committee updated on various developments over time.

Chairperson Jacobs was pleased to be invited to the discussion. The Portfolio Committee on Health had not previously engaged with role players who had been driving the technology. He appreciated the opportunity presented in this meeting. He would listen attentively to contribute to the discussion. Most Members of the Portfolio Committee on Health indicated that they would join the meeting.

Chairperson Mkhatshwa granted Members of both committees the opportunity to introduce themselves. She noted that Ms N Chirwa (EFF) was a member of both committees which could assist in bringing synergy in the work of both committees. It was important to strengthen and integrate the work of the DSI across departments. She suggested that the Committees could lobby collectively for better budget allocation for science and innovation. She called on the Department to present the exciting work that is being done at the Technology Transfer and Training Hub.

Department of Science and Innovation/Afrigen/Biovac Presentation
Dr Mmboneni Muofhe, DDG: Technology Innovation, DSI, provided a brief history of vaccine capability in the country. South Africa once had the capacity to produce vaccines. The capacity was restarted when Biovac was established in 2003, starting with the filling to packaging processes. The stage of producing our own vaccines and being self-reliant had not been reached when Covid-19 struck in 2019. Discussions on locally developed vaccines started in early 2020. The President advocated for global access to Covid-19 vaccines through the COVAX initiative. Another initiative was the call for the establishment of a technology transfer hub which South Africa was elected to host. The hub is situated at Afrigen, where the transfer of technology for vaccine production is being done with the collaboration of spokes or benefitting partners in other the low- and middle income countries (LMICs). The aim is to make sure that during this current pandemic and in future, the LMICs would have the capability to produce their own vaccines. The pandemic showed that countries that do have the capabilities were not able to produce enough vaccines to supply the whole world. The project is aimed at addressing this challenge. In building the vaccine manufacturing capabilities, the regulatory aspects need to be strengthened in all the countries involved in the project, starting with the South African Health Products Regulatory Authority (SAHPRA). Without the regulatory framework in place, it could take years for manufactured medicines and drugs to be utilised.

Dr Muofhe explained that while South Africa is in the process of developing its own capabilities, the WHO made a call for an expression of interest to host the first technology transfer hub with the view that it would be expanded in future. Towards the end of May 2021, the President and the French President, on his visit to South Africa, announced the partnership to strengthen the capacity of LMICs. This was followed in June 2021 with the announcement of South Africa as the designated host of the hub. The planning of the project started two weeks after the announcement. By September 2021, the WHO announced Argentina and Brazil as countries that would benefit from the hub. The development and training would take place at the hub and then transferred to benefitting partners or spokes. In South Africa, for example, Biovac would benefit from the first technology transfer as the spoke centred around the logistics of Covid-19 vaccines. Spokes in other countries including Argentina, Brazil, Indonesia, Bangladesh, Tunisia, Egypt and Kenya had subsequently been announced based on their responses to the call for an expression of interest. The Director-General of the WHO visited South Africa in February 2022 to observe the progress at the hub. At the time, a whole range of other spokes, which are manufacturing companies in the spoke countries, had been announced. The initiative deliberately targets local manufacturing companies in the spoke countries. On 7 March 2022, Afrigen welcomed the first spokes for training at lab-scale from Argentina and Brazil. Beyond Covid, there are a range of other diseases such as TB, malaria and HIV that are problematic to the African continent. The aim is to use the mRNA platform as the basis for building other vaccines and to develop second generation mRNA vaccines, suitable for the local markets and environments of LMICs. Some vaccines on the market have demanding storage requirements. Vaccines for the local market require stability to minimise the risks of being spoilt by temperature-related issues. Notably, the work is receiving a lot of attention as was observed during recent engagements with various stakeholders in Geneva. The work on this project would ensure that LMICs are not left behind in terms of vaccine access.

Prof Petro Terblanche, CEO, Afrigen, said the objectives and focus of this project straddle many government departments. She welcomed with great excitement the joint meeting by the two portfolios who were critical for the success of this global project which is being considered one of the biggest projects in the global south. The main objective set for this long term project is to create vaccines for equity. The manufacturing process of mRNA products differ from other products. It is a combination of a biological and a chemical process involving various manufacturing steps which require multiple disciplinary skills. The original design of this project was premised on the model that the South African consortium consisting of Afrigen, Biovac and the SAMRC would receive technology transfer from an established mRNA producer. The transfer would fast track the establishment of a hub in South Africa for clinical approval authorisation to contribute to the supply of Covid-19 vaccines. This technology transfer did not happen. But an mRNA vaccine, which is comparable to the same sequence used for the Moderna vaccine, was produced at laboratory scale in a surprisingly short period of time, grounded on the science-based technology at WITS together with Afrigen scientists. In the process, the knowledge base of WITS in using mRNA for therapeutic cancer therapy and Afrigen’s capability in understanding vaccine design and development, was combined.

Prof Terblanche explained that the capacity and capability for the current vaccine candidate would be non-inferior to the Moderna vaccine but it was not ideal for LMICs situations. Thermo stability requirements at -20 degrees are expensive and the payload for mRNA is quite high. A better thermo stability and a lower payload are being worked on in a parallel process. The first formulation of a vaccine candidate in South Africa was developed by WITS, Afrigen and UCT. The process being used is called Forward Innovation, working from the sequence that was published by Stanford University, which is also used by Moderna for vaccine development. The teams in South Africa designed the construct, the product was produced in the USA and returned to South Africa where our own knowledge base was used to design a lab-scale based vaccine. The toxicity protocols are being finalised and discussions with the SAMRC are in progress for the clinical development programme of the first candidate of locally designed and developed vaccine for Covid-19. Afrigen in partnerships with international experts are building a platform suitable for the development of multiple products. Covid-19 is the prove of concept product but the platform would be suitable for the development of other products. Because it became a green fields product with no technology transfer, process development had to start from basic lab-scale. The chemical and manufacturing processes had to be in place from the design to final production and analytics needed to be in place as a quality assurance measure.

Prof Terblanche said the company was working closely with SAHPRA, which was part of the process to get the facility fully licensed to enable vaccine production under stringent regulatory authority requirements. Facility readiness was between 14 and 90 percent depending on standing operating procedures (SOPs). More than 480 SOPs had been developed which are in various stages of implementation. Biovac assisted with some of the process developments and analytics for quality assurance. Biovac also joined in the training programme, specifically on mRNA processes. Training had been provided to spokes in Argentina, Brazil, Indonesia and Bangladesh. The current training involved the production of mRNA vaccines on laboratory scale. The next phases would involve a technology transfer from Afrigen to Biovac, for the production of industrial scale vaccines and the technology transfer back to Afrigen for transfer to the spokes to form a network for LMICs.

Dr Morena Makhoana, CEO, Biovac, highlighted the ecosystem that the initiative was helping to create. One of the biggest challenges of working in this environment was working in silos. This project created the opportunity for a biotech company to work with larger companies and universities. The initiative offered a unique opportunity for all role players to get involved in fulfilling the mandate of developing vaccines from scratch. Very few countries can boast of an ecosystem of multiple players with different roles to develop a product.  

Prof Richard Gordon, Executive Director, SAMRC, focused on the sustainability component of the project. The aim was to harness the academic horsepower of South Africa to put an end-to-end research programme together which the DSI has been funding since the start. He addressed the question of why everyone was benefitting from the research except Africa. This project was integrating the initial programme that was funded by the SAMRC and the work of other groups and universities that were operating in the same space. The aim was to use sequencing for producing vaccines with a focus on diseases in Africa. Making products suitable for the African environment hinges on the formulation of the vaccines and the lipids included in the vaccines and the mutations in the various scenarios. The goal is to develop second generation vaccines which would be suitable for Africa. The priorities for South Africa would be TB, HIV and malaria. The initial goal was to explore the possibility of developing an mRNA vaccine for TB treatment. The research on this programme had started.

Dr Muofhe remarked that the success of the initiative depends on resolving challenges in terms of the freedom to operate and the problem of the IP registration system. The system is not rigorous and allows registration without examination. As a result, broad claims of registered IPs, which had been rejected in other countries, either need to be revoked or renegotiated. He drew attention to the fact that Africa needs to purchase locally produced vaccines. It was senseless to build vaccine manufacturing capabilities on the continent while the local health departments were buying vaccines elsewhere. In other countries where local manufacturers had been successful, it had been on the basis of the support of their own countries and regions. He expressed the hope that the health departments would be the first to line up to purchase locally manufactured vaccines in South Africa. He appreciated the support from global and local stakeholders, including the local ecosystem of universities and companies and the support from government under leadership of the President who is spearheading the initiative.

Discussion
Mr T Munyai (ANC) said he was not able to make a positive contribution because he did not receive any of the documents under discussion. He questioned the absence of other BRICS and developing countries such as Russia, India and China from the project. In his opinion, the competency of these countries was comparable to Western countries. He sought clarity about claims by some companies that they were producing vaccines while their role was limited to the filling and packaging of vaccines obtained from Pfizer and other companies. He wanted to know if it was true that this problem could impact on the genetic sequencing of the vaccine or if it could corrupt the DNA. He drew attention to some scientific journals that carried reports on children in Europe and the United States of America (USA) who were developing hepatitis after being vaccinated. He indicated that he was pursuing research on this matter for academic studies. He asked for the details of the relationship between Biovac and Pfizer to be shared with the Committee. He wanted to know how the Biovac/Pfizer relationship was related to the Hub setup on the continent and how soon the system would become operational. He enquired about the IP preconditions. He asked what the reasons were for the USA receiving different vaccine batches compared to Africa. He held the view that involvement in this project should not be limited to a few stakeholders but should include more scientific and academic institutions.

Chairperson Mkhatshwa asked for an indication from the secretaries of both committees if documents had been sent to all Members and requested them to assist Members who were having challenges in this regard.

Both secretaries confirmed that documents had been distributed to all Members.  

Ms H Ismail (DA) acknowledged receiving the documents from the Committee Secretary. She asked how the side effects of the Pfizer and Moderna vaccines, which had been reported in the media, would be mitigated at production level. She wanted to know what lessons had been learned from the Sisonke trials that could be used as a learning curve in developing vaccines and what changes could be made to the process. She enquired about the timespan between the planning and developing processes of the vaccine. She asked what the timeframe was for a trial to be confirmed as an established vaccine. Covid-19 demonstrated that vaccines can be developed in a short period of time but vaccines for diseases such as TB, HIV/AIDS and malaria still require significant investment for development. She wanted to know how long it would take to produce vaccines for TB and HIV/AIDS. She asked what the potential challenges were in scaling up vaccine production and how the trials, currently in progress, would be scaled up considering the current vaccine hesitancy in the country. She sought clarity on the role of SAHPRA in this project and if there had there been discussions about the regulatory requirements for the current trials.

Ms A Gela (ANC) confirmed that she had received the documents from the Committee Secretary. She congratulated all stakeholders for the good initiative. She asked if adequate facilities were available to store the vaccines that would be produced.

Chairperson Jacobs confirmed receiving the presentation the previous day. He was surprised that the Committees had not been involved since the start of the project but would nevertheless value further engagement. He congratulated South Africa and all stakeholders working on vaccine development for being chosen as the Hub. South Africa was able to develop a vaccine regardless of the lack of technology transfer. He asked in what stage of development the vaccine candidate was. He drew attention to the concern raised by the President that locally produced vaccines were not being purchased by other countries. He wished everybody well with their efforts in developing our own ecosystem.   

Chairperson Mkhatshwa appreciated the nature of the questions from Members of the Portfolio Committee on Health. It was broadening the perspective on the topic.

Ms N Marchesi (DA) said it was exciting to note that Africa was producing vaccines on its own initiatives. She congratulated everyone involved in the project. She questioned the efficacy of the mRNA vaccine on Covid-19 considering initial announcements that the vaccines would provide 90% protection but the rate had afterwards been reduced. This was one of the reasons for vaccine hesitancy. She was aware of reports of vaccinated persons who became more ill compared to unvaccinated persons because of a drop in the Immunoglobulin A (IgA) after a couple of months. The mRNA genome was suspected to cause reverse transcription in the liver. She asked if the matter was of concern to researchers involved in this project and if an analysis of the clinical trials had been done. Reports in the New England Journal of Medicine indicated that vaccine lowers immune defence and increase susceptibility to other diseases. She asked how the efficacy of the mRNA vaccine would be guaranteed and if more light could be shed on the side effects on smaller groups. Information on the performance of Covid-19 vaccines was not widely spread. Talks of moving on from the booster shot to the fourth or fifth doses proved that the efficacy of 90% was not true. In her opinion, exposure to Covid-19 created more protection due to the higher IgA. Vaccines used for normal colds provide 50% protection whereas Covid-19 vaccine protection was reported to drop below 50%. She asked how the mRNA vaccine could protect against Covid-19 if the IgA is reduced after a couple of months.

Ms N Chirwa (EFF) asked for an explanation on the insistence on using the mRNA technology. She requested a list of all government and private sector stakeholders. She wanted to know what role SAHPRA was playing and if other external entities were participating in the project. She enquired about the cost of the project considering the low vaccine uptake. In her opinion, the National Department of Health was not transparent in terms of educating citizens hence the low response from young people. She wanted to know who the funders of the project were. According to SAHPRA, the FDA participated in the project but the USA was not recognising SAHPRA as a stakeholder. She sought clarity on who owned the right to the project under discussion. She enquired about the level of integration with higher education institutions on this project.

Mr W Letsie (ANC) noted that funding challenges had been raised in numerous engagements with the Department. He expected the issue to have been highlighted in the presentation in anticipation that both Committees would jointly address the matter. He complained that the Department was silent on the funding challenges.

Dr W Boshoff (FF+) said he would limit himself to welcoming the presentation as all his questions had been raised by his colleagues. He was impressed by the technological ability available in South Africa and that it was functional and world class. He shared the example of his sister who took part in an mRNA trial for colon cancer treatment. As a result of the treatment, she has not experienced a recurrence of the disease for the past six years. He therefore had a firm trust that the technology will prove to be of vital importance. He was making his contribution as a non-scientific person to provide assurance to people who are sceptical.

Chairperson Mkhatshwa noted the concerns of Dr Muofhe about the freedom to locally produce and sell products and about the IP system not being rigorous. She encouraged the Department to approach the Committee for assistance in this regard. She called on the Department to respond to the questions and comments from Members.

Dr Muofhe appreciated the nature of the engagement from Members. He explained that countries needed to apply to be considered as a host country of this project. South Africa applied and was successful. Other countries either did not apply or their applications were unsuccessful. The majority of countries chose not to apply. Some countries, such as India had their own manufacturing capacity for a variety of drugs. He clarified that SAHPRA cannot be involved in production because it is a regulatory body. SAHPRA was supposed to benefit from Pfizer in terms of strengthening its regulatory capacity to ensure the success of the project. In response to Ms Chirwa, he said the mRNA initiative was about mRNA technology which proved to be an ideal platform that could be used beyond Covid-19. A list of stakeholders would be provided to the Committee. The project resulted from a concern by the World Health Organisation (WHO) that lower and middle income countries (LMICs) were at the back of the queue in terms of vaccine distribution. The WHO decided to implement the project to prepare for further outbreaks. It was important for LMICs to build their own capabilities. South Africa was elected as the host country with the support of a number of governments. The initiative is invested in hosting capabilities in the fields of genomic surveillance, clinical trials and fill-finish processes. Support for the project was led by the WHO which resolved the funding problems in terms of technical assistance and equipment. Higher education is part of the ecosystem because the bulk of the research is being done at universities. The horsepower of all South African institutions is used to ensure the success of the project. The majority of researchers on the project are local scientists as demonstrated in the number of presentations that were done on genome sequencing. The capacity building programme is evidence of the Department’s commitment to the transformation agenda.

Prof Gordon said the Council identified gaps in capacity development. A scholarship programme to build a cohort of researchers from historically disadvantaged institutions was announced. Responding to the concerns about the side effects of the vaccine, he said it was important to recognise that Covid is not a new virus but that Covid-19 is a novel variant of the virus. Covid is a common cold that mutates quickly. It was therefore not unusual to lose immunity after a couple of months and it was unlikely for one vaccine to cover different variants. He suggested that the Committee meet with the Vaccine Advisory Committee (VAC) for more information on the side effects of vaccines. He explained that the original focus of mRNA technology, was cancer treatment. Time scale was the big attraction to mRNA technology because of the speed with which Covid-19 was mutating. He was unable to comment on people who fell ill after being vaccinated but said in general it was unlikely but there could be some outliers because people respond differently to vaccines.

Dr Makhoana clarified the difference between Pfizer and mRNA in terms of an analogy in the motor car industry. Mercedes and Toyota have local assembly points but the IP designs are in the host countries, i.e. Germany and Japan. The Biovac relationship with Pfizer was not related to the Hub. From the manufacturing perspective, Biovac fill, pack and label the vials but does not have the IP and manufacturing knowledge. Capacity was needed, from the development to the distribution processes. But Pfizer was not willing to share the raw material IP. For this reason, the work of the Hub became important. Biovac gained some experience from working with Pfizer which enabled the entity to handle the formulation fill-finish processes of Pfizer products at storage levels of -70 degrees, which was new to the country, and the Johnson & Johnson vaccine at -20 degrees. It was important to develop the downstream capability so that Biovac could be thermo-ready once Afrigen and the team have developed their product. The capability that Biovac had developed would serve the activities of the hub.

Prof Terblanche said the extent of the questions from Members demonstrated the importance of this project. She explained some of the key reasons why the WHO and its partners chose the hub as a global programme to build on an mRNA platform. The mRNA technology is used because it is non-live, meaning that it does not include any live pathogens, it is sequence specific and can be replicated, duplicated and used in the production of the virus. It lends itself to great flexibility, i.e. it has the ability to make a specific variant of a virus. The safety component entails that mRNA does not integrate into the human genome system. It degrades the moment it is recognised by the body. The two mRNA approved vaccines have full market authorisation. More than 8 billion doses have been administered to people. The vaccines induce a potent human response. The current vaccines have demonstrated very effective immune responses and have clinically demonstrated to prevent death and cases of severe hospitalisation. It provides at least six to nine months of protection. The manufacturing process is an invitro transcription method, meaning there are no cell cultures involved and it is very scalable. For example, with a five litre bag of the drug product, which is pre-formulation, close to ten million vaccine doses.

Prof Terblanche confirmed that Afrigen had several consultations with SAPHRA because of the critical role it had to play in the licensing of the facility, to ensure that all standards were met for the production of safe vaccines. SAPHRA also plays a role in the approval of clinical trials. The mRNA vaccine candidate is undergoing stringent safety testing in pre-clinical settings in a laboratory and also in animal testing to ensure that safety profiles are optimised and that efficacy is reached before the clinical trials to vaccinate humans take place. She assured Members that the utmost safety measures are considered in this development. She emphasised that the facility could not operate without power supply. The system is supported by a battery back-up or uninterrupted power supply to fuel the critical components in case of a power failure when the diesel generator is activated. The system could not solely rely on solar and renewable energy. She explained that the mRNA global IP landscape is very active. Original mRNA development started in the 1960s focusing on therapeutic uses for cancer. The same platforms were used for the development of vaccines for the ZIKA and Lassa fever viruses which made it possible to fast track the development in 2020 of Covid-19 vaccines. But because the platform has become so attractive and lends itself to so many benefits, thousands of patents are being filed as the landscape unfolds. It was important to note that there are patents that would block the ability of the hub to produce and market the Covid vaccine because of the IP restrictions in some of the territories in the hub network. Therefore, the trips waiver is an important discussion as well as the voluntary waivers that Moderna and BioNTech have declared to not stand in the way of LMICs to use the technology in the production of mRNA vaccines. The challenge is that the South African patent system was a non-examining system. Moderna filed a patent in South Africa, claiming the right to any vaccine containing mRNA. This is presenting a problem for this platform and unless this particular patent is addressed, the hub is prevented from producing any Covid, HIV, TB or flu vaccine or any of the neglected diseases which pose a burden of diseases for LMICs. The claim by Moderna had been rejected in the USA and in Europe, China, Australia, Japan and in all the major economies but because of our non-examining system, these claims were approved in South Africa. She was pleased to confirm that the government through the DSI had been assisting the hub with the freedom to operate. An alternative way to address the issue is through in-house innovation by South African scientists, engineers and other partners by using different lipids and processing with different ratios, thereby developing our own knowledge base to provide the freedom to operate.

Dr Muofhe encouraged the Committee to visit the facility sooner rather than later. The facility would soon be closing for the SAHPRA inspection. The Department offered to arrange the site visit on behalf of both Committees.

Prof Terblanche advised that the visit could be hosted before the end of July 2022, when it closes for inspection by the viewing panels.

Chairperson Mkhatshwa noted the time limit to arrange the site visit. She requested Members indicate their availability considering that Parliament was due for recess. It was important to have joint sittings on the matter of expanding locally produced content. She proposed further engagement to expand the discussion on IP and SAHPRA in relation to the regulatory environment. It was important to discuss skills development. She noted the observations and concerns of Members. Key issues identified may require further interaction with other departments and committees. She urged Members to submit requests for further information via email and to indicate preferred dates for the site visit.

Chairperson Jacobs noticed that questions were answered well. The medical jargon was not easy to explain in general terms and required a particular understanding of the topic which not all of the Members had. It impressed the need to have joint meetings to discuss critical issues. He called for another joint meeting to discuss matters related to the training of medical students and specialists.

Chairperson Mkhatshwa requested the secretaries to work together in arranging the site visit. She agreed that the work of the committees is strengthened by having joint discussions. The Portfolio Committee on Health should feel free to engage the Portfolio Committee on Higher Education on challenges in education, science and innovation.

The meeting was adjourned.