A recent article published by HPW based on research by Matthew Herder and Ximena Benavides made several criticisms and observations about the mRNA programme. HPW asked the mRNA co-leaders, the MPP and WHO, to respond to the issues raised and this is their response. 

The mRNA Technology Transfer Programme, established by the World Health Organization (WHO) in partnership with the Medicines Patent Pool (MPP), was launched in July 2021 in response to the COVID-19 pandemic to address the global inequities in vaccine manufacturing. Its primary aim is to build mRNA vaccine manufacturing capacity in low- and middle-income countries (LMICs), thus bolstering health security through local and regional production.

A key component of the Programme is the South African Consortium, which consists of Afrigen, Biovac, and the South African Medical Research Council (SAMRC). The consortium, with the contribution of other research organizations in South Africa, is responsible for developing an mRNA-based technology platform (with Afrigen focusing on pre-clinical and early clinical scales and Biovac handling late clinical and commercial scales) and vaccine candidates tailored to the needs of LMICs, with the objective being to transfer them to a network of technology recipients called Programme Partners within LMICs.

Alongside the South African Consortium, the Programme brings together a range of international and local partners who are critical players in developing and transferring vaccine technology to LMICs. The initiative receives support from donors such as Belgium, Canada, the European Commission, France, Germany, Norway, South Africa, and the ELMA Foundation.

The Programme’s four primary objectives are:

1. Establishing sustainable mRNA vaccine manufacturing capacity in regions with limited production ability;
2. Introducing new technologies and promoting research and development (R&D) in LMICs;
3. Strengthening regional biomanufacturing capacity through knowledge-sharing and workforce development;
4. Developing regulatory capabilities to support the approval and distribution of vaccines in LMICs.

 Establishment and structure 

The Programme emerged from a critical need recognized during the COVID-19 pandemic, as it became evident that LMICs lacked the capacity to produce medical countermeasures, particularly vaccines. 

France suggested establishing a fifth ACT Accelerator (ACT-A) pillar to address this gap. Following discussions within ACT-A, and given the urgency of vaccine production, the initiative translated into a Vaccines Manufacturing Taskforce established under ACT-A’s vaccine pillar, COVAX, with three workstreams. Workstreams 1 and 2 focused on addressing immediate challenges, such as supply bottlenecks, while Workstream 3 took on the longer-term goal of establishing vaccine production in LMICs.

Due to its expertise in licensing and legal matters, WHO asked the UN-backed Medicines Patent Pool to co-facilitate Workstream 3. Following guidance from WHO’s Product Development for Vaccines Advisory Committee, Workstream 3 focused on mRNA technology, ultimately evolving into the mRNA Technology Transfer Programme. 

With the completion of Workstreams 1 and 2, the Vaccines Manufacturing Taskforce was sunset, and the Programme moved into WHO’s Access to Medicines and Health Products division.

Every company that applied to the Expression of Interest launched by WHO in November 2021 to be a recipient of mRNA technology through the WHO selection process was accepted, barring any technical issues. In the Pan-American region, the Pan-American Health Organization led its own selection process, resulting in the choice of one company each from Argentina and Brazil. 

All companies were required to have the backing 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 broad mRNA production capacity across LMICs globally.

Governance

Oversight of the Programme rests with WHO, which regularly engages with its Member States through meetings to provide updates and gather input. Additionally, quarterly meetings are held with Programme funders and civil society.

To assist in decision-making, WHO established the Scientific and Technical Review Committee (STeRCo), which provides advisory support to the WHO secretariat on critical technical matters. The STeRCo consists of independent experts and stakeholders, including representatives of the Civil Society, who guide WHO on areas essential to achieving the Programme’s objectives, such as:

• Strategic direction, including the evaluation of technologies for implementation and transfer;
• Pre-clinical and clinical development plans for relevant mRNA technologies;
• Adherence to regulatory guidelines;
• Value for money in fund allocation;
• Other critical issues to ensure the successful execution of the Programme.

From the outset, the South African Government and Africa CDC have been integral members of the STeRCo, ensuring their perspectives are included in decision-making. This inclusive approach is central to fostering local ownership and keeping the Programme responsive to the needs of LMICs.  Additionally, MPP convened an mRNA Scientific Advisory Committee (mSAC), comprising internationally recognized experts in mRNA vaccine development, to provide top-tier scientific input into the Programme.

Knowledge sharing and empowerment of LMIC partners

A cornerstone of the programme is knowledge sharing and empowerment of LMIC partners. For instance, Afrigen and Biovac, both part-owned by the South African government, play a central role in developing and transferring the mRNA technology platform, developed with a specific COVID-19 vaccine variant as proof of concept, to 14 companies across multiple regions. The South African Medical Research Council (SAMRC) shares knowledge with the network of partners on second-generation mRNA technologies and vaccine candidates targeting other diseases.

All partners benefit from MPP’s licensing model, which ensures consistency across the Programme by offering non-exclusive royalty-free licenses in LMICs, allowing equitable access to the developed technologies.

In addition to the core governance framework, it is important to highlight the continuous engagement and collaborative efforts between the partners. These include regular calls with all partners, and participation in significant global conferences, such as the Developing Countries Vaccine Manufacturers Network (DCVMN), and other major conferences.

The partners frequently present their progress during various meetings, including Clinical Study (CS) meetings and Research & Development (R&D) events. Additionally, WHO carries out government engagement missions as an integral part of this collaborative process. These efforts ensure that all stakeholders are aligned and informed of the programmes work.

Role of WHO and MPP in supporting the Programme

The role of WHO and MPP, the co-facilitators of the Programme, is to support and empower. An example of this are the research and development consortia, whose creation amongst the entities involved in the Programme is being supported by WHO and MPP, and each consortium  is each being led by a research organisation also includes one or more Programme Partners.

These consortia are completely autonomous in deciding where to focus their efforts. In addition, as part of the Programme, WHO launched a bio-manufacturing training programme for people in LMICs to ensure availability of skilled local workforce in the manufacturing and regulatory fields to sustain the production of biologic countermeasures both during and between pandemics.

 Licensing and intellectual property (IP) strategies

Because the role of WHO and MPP is to support and empower rather than control, the Programme imposes as few conditions on the participants as possible. The major conditionality is the requirement for partners to license the intellectual property they develop to MPP, allowing MPP to sub-license it to other Programme Partners.

This model, which MPP has used for other products, encourages competition, ensuring affordability while maintaining sustainability for manufacturers. A notable example of this approach is the first-line HIV treatment regimen, which MPP sub-licensed to manufacturers, enabling the Global Fund to procure it at less than $40 per person per year—the lowest price ever achieved for such a regimen. This price reduction was driven by competition and innovation, particularly in manufacturing process optimization.

Technology transfer and capacity building

MPP’s technology transfer team plays a central role in providing technical advice, project management, and oversight during the various phases of technology development and transfer.

While MPP does not engage directly in laboratory work, it facilitates the transfer of expertise, evaluates infrastructure needs, engages with external entities supporting analytical work, and assesses workforce training requirements. A multilateral staggered technology transfer approach was adopted to expedite the process, allowing partners to access essential information as it became available.

This early access provided the Partners with the opportunity to familiarize themselves with the fundamentals of mRNA technology while Afrigen continued its initial development. MPP’s role is to support Afrigen and Biovac in developing the mRNA platform (processes and analytics) and act as an intermediary, fielding numerous requests from partners about facility designs, equipment and material specifications, process descriptions, and troubleshooting. 

By doing so, MPP ensures that Afrigen and Biovac can focus on technology development while still addressing the needs of the manufacturing Partners. This approach has been successful, so far.

Afrigen has now established an mRNA manufacturing platform at a 1 litre IVT scale and initiated the transfer of the technology to Biovac earlier this year by providing an on-site technology platform demonstration. The remaining technology platform demonstrations at Afrigen to the Programme Partners are set to begin in Q4 2024 and continue into 2025.

 Sustaining the Programme

The primary goal of the mRNA Technology Transfer Programme is to ensure that LMICs have the mRNA capacity and capability to respond to the next pandemic. To achieve this, however, it is necessary to keep manufacturing facilities ‘warm’ by producing mRNA products between pandemics. 

Since the timing of the next pandemic is unknown, and there is little appetite for indefinite subsidies, these products must have viable markets and generate a constant stream of adequate revenues. 

This was a critical lesson from WHO’s earlier influenza technology transfer initiative. Just as important to sustainability is the role of government in each of the Programme Partner’s countries. Policies must be adapted to favour the investment being made, and this includes strengthening the National Regulatory Authority, which will require an investment of time and resources. 

Changes in procurement practices across countries and regions may need to be made along with data sharing to estimate demand. Building a robust ecosystem in LMICs is an area of urgent priority. From the outset, Programme Partners and recipient countries were informed that they would need to secure their own financing, as the Programme itself would not be providing funding. 

However, France and Canada made additional funding available for specific countries. This extra funding has not influenced or distorted the Programme’s overall direction. All partners will eventually receive some level of support. However, the extent of this support may vary depending on donor preferences and whether the recipient is a public or private entity.

Additionally, the Programme has not encountered any high-income countries (HICs) unwilling to support the development or transfer of upstream inputs, such as novel lipid nanoparticles (LNPs) and antigens. 

Currently, the Programme is funded until 2026. While additional funding is required to complete the year, the goal is to complete the transfer of technology to the majority of partners by that time. The Programme coordinators are working with partners to develop sustainable business models and explore new funding sources to ensure operations can continue beyond 2026.

A major part of this sustainability strategy is the creation of R&D consortia focused on developing vaccines for diseases relevant to LMICs. These consortia bring together Programme Partners, companies, research centers, and universities to collaborate on the development of vaccines and therapeutics using the mRNA platform. 

So far, four consortia have been established in Southeast Asia, working to develop preventive mRNA vaccines against dengue, Plasmodium Vivax malaria and human hand, foot and mouth disease and a therapeutic human papillomavirus mRNA vaccine. 

Ongoing R&D work is also focused on RSV, Rift Valley Fever, gonorrhoea, HIV, and tuberculosis. In a recent meeting in Brazil, three more consortia were proposed, focusing on influenza (pandemic and seasonal), leishmaniasis, and novel lipids.

Conclusion

The mRNA Technology Transfer Programme is a landmark initiative aimed at addressing the inequities in global vaccine production by empowering LMICs to develop and produce their own vaccines. 

Through a combination of technical support, knowledge-sharing, and innovative licensing strategies, the Programme is creating a sustainable model for mRNA vaccine production that will enable LMICs to respond to future public health challenges. 

As it looks beyond 2026, the Programme remains focused on ensuring its long-term viability and expanding its impact across LMICs, contributing to global health security for the years to come.

Image Credits: WHO, WHO , Kerry Cullinan, WHO.