Typically, technology transfer is a bilateral process – from the originator of the technology (Sending Unit – SU) to a single recipient (Receiving Unit – RU).

The mRNA Technology Transfer Programme utilises a multilateral technology transfer model, where the technology is transferred from a single originator (SU, Afrigen and Biovac) to multiple recipients (mRNA Programme Partners).

Geographical Expansion: Transferring the technology to new regions or countries to enable local production, which is common in global health initiatives to address access issues (as for the mRNA Programme).
Scaling Up: Moving a drug from a small-scale lab setting to a large-scale commercial production environment.
Contract Manufacturing: Engaging a third-party contract manufacturing organization (CMO) to produce the drug.
Lifecycle Management:Improving the production process over time or adapting it for new formulations or delivery systems.

The Programme aims at accelerating access to know-how and capacity building for the mRNA technology platform. Starting from R&D small scale, technology recipients can familiarise themselves with the technology. Additionally, the recipients can start building the competences needed to implement mRNA-based products and gain confidence at small scale on the procedures and essential parameters to prepare the next steps of technology transfer.

• Process and Methods Transfer: This includes transferring the manufacturing processes, analytical methods, quality control procedures, and formulation techniques from one site to another, ensuring that the product is produced consistently and meets established quality standards.
• Documentation and Data: Detailed documentation, including standard operating procedures (SOPs), batch records, and methods qualification protocols and results, is transferred to ensure that the new site can replicate the manufacturing process exactly.
• Training and Support: Training is provided to the receiving unit to ensure that staff understand how to operate equipment, manage processes, and maintain product quality.
• Regulatory Compliance: Both the sending and receiving units must ensure that the transferred technology complies with Good Manufacturing Practices (GMP) and local regulatory requirements (as applicable).

The Partners are collaborating closely with MPP for the definition of gaps and needs for the initial onboarding of the technology platform in their facility and also during the readiness phase. The technology transfer documentation will be prepared by Afrigen and Biovac and will be shared with the Partners as soon as it is finalized. The list of documents to be included in the technology transfer packages is defined by Afrigen and Biovac with the support of MPP. The Partners will attend in 2024-2025 at Afrigen a Sending Unit technology platform demonstration at 100ml or 1L in-vitro transcription scale (including process and analytical methods) and then do technology transfer demonstration based on a Plan agreed with Afrigen and MPP in their facility.

There are several factors that make mRNA technology attractive to the Programme:

• mRNA vaccines have proved efficacious against COVID-19 caused by the ancestral SARS-CoV-2 Wuhan strain and against cross-reactive new variants proving to be a useful tool to guarantee a rapid response to outbreaks.
• Though relatively new, the mRNA vaccine manufacturing technology platform is easy to share, develop, scale-up and adapt to other disease targets.
• This technology allows for producing high numbers of doses at a relatively small facility footprint, compared to other vaccine technologies, making it suitable for LMICs.

COVID-19 was the only disease for which an mRNA vaccine was approved at the time the Programme as initiated . A proof of concept should have been established by manufacturing a vaccine for which a reference product was available to demonstrate its immunogenicity, safety and efficacy.

• Establishing sustainable mRNA vaccine manufacturing capacity in regions with limited production ability;

• Introducing new technologies and promoting research and development (R&D) in LMICs;

• Strengthening regional biomanufacturing capacity through knowledge-sharing and workforce development;

• Developing regulatory capabilities to support the approval and distribution of vaccines in LMICs

https://medicinespatentpool.org/uploads/2024/02/MoU-between-WHO-and-MPP-signed-by-WHO-and-MPP-Jan-2024-1.pdf

14 Partners in 14 different countries have been selected and announced by WHO in 2022.

Sinergium in Argentina and Bio-Manguinhos in Brazil were nominated by PAHO in September 2021. The other 12 Partners were nominated by WHO in February-April 2022 as a result of an EOI opened in November 2021.

WHO and the Medicines Patent Pool: Programme co-conveners.

South African consortium: selected by WHO in June 2021, following an Expression of Interest issued in April 2021 to companies interested in hosting an mRNA technology transfer hub. The consortium is responsible for developing an mRNA technology platform and transferring it to manufacturers in LMICs (technology recipients). The South African Consortium includes the following organisations:

• Afrigen:technology platform development (using COVID-19 as proof of concept) up to earllyClinical trialscale (Phase I/II) and technology transfer to the Programme Manufacturing Partners (including in-person batch manufacturing demonstration).
• Biovac:recipient of the technology platform developed by Afrigen and responsible for technology platform optimisation, robustness and scale-up (up to Clinical trial Phase III scale), and technology transfer to Programme Manufacturing Partners.

• South Africa Medical Research Council (SAMRC): coordinating research efforts on next generation improved mRNA technologies (manufacturing process and vaccine composition) and early development of vaccine candidates targeting diseases relevant for LMICs. SAMRC coordinates research activities of different organisations in South Africa (South African mRNA Vaccine Consortium – SAMVAC): Antiviral Gene Therapy Research Unit (AGTRU-University of Witwatersrand (WITS))
• The Genomic Surveillance Network of South Africa (NGS-SA)
• Kwazulu-Natal Research Innovation and Sequencing Platform (KRISP)
• Centre for Epidemic Response and Innovation (CERI-Stellenbosch University)
• African Centre of Excellence for Genomics of Infectious Diseases (ACEGID)
• Centre for Bioprocess Engineering Research (CeBER, University of Cape Town (UCT)), and the DSI Preclinical Drug Development Platform (PCDDP, North-West University).

mRNA Programme Partners: 14 technology recipients, supported by their respective governments, nominated by WHO between February and April 2022, following an Expression of Interest launched by WHO in November 2021 (see picture below).

All the manufacturers that applied to the Expression of Interest launched by WHO in November 2021 to receive mRNA technology through the WHO selection process were accepted, except in cases where there were technical issues. In the Pan-American region, the Pan-American Health Organization led its own selection process, resulting in the selection of one company each from Argentina and Brazil. All companies were required to have the support of their respective governments. With two recipients in South America, six in Africa (including Biovac), two in Eastern Europe, and five in Asia, the Programme ensures a broad mRNA production capacity across LMICs globally

The model adopted by the mRNA Programme is a multi-lateral technology transfer, where the South African consortium is responsible to develop an mRNA-based vaccine manufacturing platform (process and analytics) and to transfer it to the Programme Partners (technology recipients). All selected recipients will have access to technology transfer documentation packages at different stages of the platform development performed by Afrigen and Biovac. Following technology transfer, the recipients will decide whether they have interest to further develop/ commercialize a COVID-19 vaccine (based on current -Oct 2024 epidemiological situation this has been assesses by the Partners as very unlikely) or apply the technology platform to other pathogens of interest. Once a vaccine has been successfully developed, the recipients will be able to increase the process scale to enable supply of mRNA vaccines to support local and regional requirements. Each recipient will need to seek regulatory approval for the vaccine in their jurisdiction.

Following the signature of the Technology Transfer Agreement, MPP, together with WHO, has engaged with each recipient to define the Technology Transfer Strategy. The recipients’ strategic intent and business plans will guide their technology transfer strategy considering both future pandemic readiness and inter-pandemic sustainability.

Technology transfer Package 1: Access to R&D mRNA technology platform (up to 1L IVT scale, suitable for early phase clinical trials). Enables the recipient to develop mRNA expertise at a scale commensurate with early-stage clinical trial material supply. This is suitable for partners intending to implement an internal platform for new vaccines development (up to Phase I/II).

Technology transfer Package 2a: Access to an optimized and industrialized technology platform at a scale suitable for early phase clinical trials. Enables partners to implement adapt the mRNA technology platform to disease targets other than COVID-19.

Technology transfer Package 2: Access to scaled-up technology platform for a COVID-19 mRNA vaccine (up to 10L IVT).

Afrigen is developing both the product and processes, including analytical methods, for mRNA-based manufacturing. This platform will be shared with 15 recipients. If each recipient were to develop the platform independently, it would inefficiently use valuable resources, especially as some may lack the capacity. By centralizing the development at Afrigen, all recipients gain access to ready-made knowledge and established procedures, eliminating the need for their own development investments.

The Programme is currently funded by: Belgium, Canada, the European Commission, France, Germany, Norway, South Africa, and the ELMA Foundation

The Programme has organically expanded its outlook considerably since inception. In March 2024, four scientific R&D consortia were established in Southeast Asia to explore R&D in disease areas such as Dengue, malaria vivax, Hand foot and mouth diseases and HPV to develop preventive or therapeutic vaccines (for HPV). Additionally, RSV, HIV, and TB are gaining traction in R&D efforts. Additional consortia are expected to be formed in and across all other regions. Sinergium has announced its work on an H5N1 vaccine candidate.

The platform developed as part of the mRNA Programme is generating significant interest from Programme Partners to advance mRNA vaccine research further in multiple disease areas.

Programme funds have enabled the establishment at Afrigen of: – a fully equipped end-to-end manufacturing facility at Afrigen (expected to receive GMP accreditation by SAHPRA, the national regulatory authority by Q3 2025) including pDNA, bulk Drug Substance, bulk Drug product, Fill and Finish and Quality Control areas suitable for the manufacturing of mRNA-based products; – and a fully equipped R&D facility.

Programme funds have enabled the establishment at Biovac of: a multi-purpose GMP suite suitable for manufacturing of bulk Drug Substance bulk Drug Product.

Afrigen has established a non-GMP COVID-19 vaccine manufacturing platform at a scale suitable for manufacturing a vaccine batch to be used in a Phase I/ II clinical trial in a GMP environment. Safety immunogenicity and efficacy of the vaccine candidate manufactured by Afrigen has been demonstrated in pre-clinical studies (mice, rats, hamsters and Non-human primates). Technology transfer of the documentation produced has happened in parallel to the development and demonstration of the manufacturing platform to the Programme partners has started in October 2025 and will continued to the whole 2025.

No, clinical development of the vaccine has been discontinued for the following reasons.

• Efficacy and safety of Afrigen’s COVID-19 candidate comparable to commercial products has been demonstrated in preclinical rodent and non-human primate studies.
• COVID-19 epidemiology has significantly changed and mRNA programme Partners have shown reduced interest in technology transfer of COVID-19 vaccines.
• Reduced likelihood an adequate comparator vaccine will be available in South Africa at clinical trial onset.
• Other vaccine candidates of higher commercial interest can potentially be ready soon for
• The urgency to complete the platform technology transfer to Partners who are rapidly building infrastructure.

No, the solid pre-clinical data generated will support the transfer of the platform to Biovac (and other partners). Biovac will proceed with the industrialization and scale-up of the platform as planned.

No, Afrigen is developing its own COVID-19 mRNA vaccine (Afrivac2121). The composition of Afrivac2121 mimics the Moderna COVID-19 vaccine, according to publicly available information. The manufacturing process is being entirely designed at Afrigen.

Within the broader context of promoting local production, technology transfer alone is insufficient. Two major barriers need to be overcome – the low availability of a trained workforce and weak regulatory capacity.

WHO is addressing these gaps by establishing a biomanufacturing workforce training hub and working with the WHO Academy to ensure that regulatory and biomanufacturing training meets countries’ needs and objectives.

Regulatory systems play a key role in assuring the quality, safety, and efficacy of medical products and in licensing them so that they may be made available to populations. WHO is working with multiple regulatory authorities in countries that are participating in the mRNA technology transfer Programme by evaluating them through its global benchmarking tool (GBT).

The tool and benchmarking methodology enable WHO and regulatory authorities to identify strengths and gaps and build improvement plans. Once improvements have been made, the regulatory authority is assessed according to its maturity level on a scale that ranges from 1 (existence of some elements of a regulatory system) to 4 (operating at advanced level of performance and continuous improvement).

WHO intends to use the GBT to evaluate and publicly designate WHO-listed authorities (WLAs) that have been objectively documented to perform at maturity levels 3 and 4. Several countries involved in the Programme are at an advanced stage of being assessed for their maturity level.

With regards to Afrivac2121 COVID-19 vaccine, the South African Consortium used publicly available information regarding the composition of the Moderna Spikevax COVID-19 vaccine (mRNA sequence and lipids composition) and has independently developed the manufacturing process and analytical methods.

The South African Consortium, in collaboration with South African academic groups and biotech companies outside of South Africa are developing next generation mRNA vaccine technologies. Intellectual property resulting from this activity will be held by the inventors but will be made freely available to the recipients to the mRNA Technology Transfer Programme (Manufacturing Partners).

Likewise, the R&D consortia formed under the umbrella of the mRNA Programme (see also Q17) that will work to develop mRNA-based vaccines against other diseases relevant for LMICs and contribute to the sustainability strategy of the manufacturing partners will make available the results of their research efforts to the Programme Manufacturing Partners.

The Medicines Patent Pool (MPP) – which co-leads the Programme initiatives with WHO – will assist with its expertise in intellectual property management by providing intellectual property analysis and defining and negotiating terms and conditions of agreements that might have to be signed.

Freedom to Operate (FTO): MPP and WHO will not guarantee FTO at country level but will provide an Intellectual Property landscape analysis detailed at country level. The check of actual status of patents/ claims filed and/or granted in the country is the recipient’s responsibility.

Intellectual Property sharing: Novel and inventive data generated by the recipient in the framework of the Programme and/or through data received from the Programme will be shared with other recipients in the Programme.

Third party Intellectual property: If recipients are granted access to third party IP, they have the obligation to undertake reasonable efforts to license that IP to MPP (and the Programme) only if the IP is linked to the research, development or commercialisation of a product partially or entirely based on the technology transferred.

WHO does not procure vaccines, but recipients are encouraged to seek WHO pre-qualification (PQ) of the vaccines they produce which is a requirement for the vaccines to be procured by international agencies (GAVI, UNICEF, Revolving Fund, etc.).