Study of mRNA transfer programme hub finds weaknesses

by Charlotte Kilpatrick | Oct 1, 2024 | Global Health | 0 comments

A study in PLOS Global Public Health in September 2024 compares the WHO and Medicines Patent Pool (MPP) mRNA technology transfer programme with the approach and practices of current biopharmaceutical production. The programme launched in June 2021, with a hub in South Africa, and is intended to increase vaccine manufacturing capacity in low- and middle-income countries (LMICs) in response to the “vaccine apartheid” of the COVID-19 pandemic. The study finds that, despite improvements to the sharing of knowledge, other features are “in line with the status quo”.  

Addressing “vaccine apartheid” 

During the COVID-19 pandemic “vaccine apartheid” was used to describe the unequal distribution of vaccines against COVID-19. To address this disparity, WHO chose Afrigen Biologics to “change the global landscape of biopharmaceutical production” by developing an mRNA COVID-19 vaccine and distributing the technology to manufacturers in low- and middle-income countries (LMICs).  

“Building capacity to make vaccines locally for local populations became imperative.” 

WHO identified a model of knowledge-sharing that had been used in efforts to make the global influenza virus sharing network more accessible and useful to people in LMICs. The Medicines Patent Pool (MPP) was assigned the responsibility of managing the mRNA programme’s fundraising and legal needs.  

“The programme has the potential to be transformative as a model of vaccine production, encompassing both upstream research and development (R&D), and ‘end-to-end’ vaccine manufacturing.” 

However, the initiative faces “several risks”, such as “precarious levels of funding”, the threat of patent litigation by establish manufacturers, and a variety of governance issues as it seeks to develop the capacity for producing high-quality mRNA-based technologies to protect against a range of diseases.  

The study 

The authors used qualitative research methods to explore the extent to which the WHO/MPP-managed programme differs from current biopharmaceutical production. The “situational analysis” combined data collection and analysis of multiple data sources. In document analysis they analysed “multiple types of documents”, including legal documents, agreements, correspondence, and patent applications.  

The approach also involved a purposive sampling strategy, engaging people in leadership positions. Interviews were conducted with executives and officials, scientists, WHO and MPP officials (the “programme’s architects”), representatives from vaccine manufacturers across the world (“programme partners”), and scientists and experts from the global North. The study begins by exploring the programme’s origins, from 2020 to 2021, before comparing its design to four paradigmatic features of global biopharmaceutical production as identified in literature and “numerous scholarly disciplines”: 

1. Weak conditionalities attached to publicly funded science 
2. Secret, transactional R&D partnerships 
3. A high degree of financialization 
4. Market-based governance 

The origin story 

The authors describe WHO’s efforts to improve access to COVID-19 interventions as “markedly” different in approaches to mitigating access challenges and the actors involved.  

The Access to COVID-19 Tools Accelerator (ACT-A), launched in April 2020, combined public and private actors. The vaccine arm of ACT-A, COVID-19 Vaccines Global Access (COVAX), was intended to procure vaccines for LMICs through the collective purchasing power of high-income countries (HICs). However, this effort was hampered by HICs prioritising domestic populations, “at the expense of equitable global distribution”.  

The COVID-19 Technology Access Pool (C-TAP) was established in May 2020, contrasting ACT-A’s charity-based approach with an effort to distribute control of intellectual property (IP), data, and knowledge. This “pooling” of technologies to address population needs in LMICs was “applauded by civil society but fiercely contested by industry, its allies, and the Gates Foundation”.  

A third proposal emerged, centred on building capacity “in LMICs for LMICs”, driven by WHO’s lead coordinator for vaccine research, Dr Martin Friede, and Chair of MPP’s Governance Board and former WHO Assistant Director-General, Dr Marie-Paule Kieny. They reflected on the “hub and spoke” model of manufacturing that had been used in the context of influenza vaccines, imagining a “centralised knowledge sharing system with a view to enhancing local vaccine production capacity in LMICs”. There were “crucial questions” about how this model would work in the context of COVID-19.  

WHO’s Erika Dueñas Loayza suggested that the initial plan was to embed the COVID-19 hub within C-TAP. In the face of growing industry opposition to C-TAP, the WHO Assistant Director General of Access to Medicines and Health Products at the time, Dr Mariângela Simão, and WHO Chief Scientist at the time, Dr Soumya Swaminathan, elected to move the programme closer to the ACT-A. In this context, WHO issued a call for expressions of interest for technology transfer hubs in April 2021.  

Afrigen responded to this call, with Chief Executive Professor Petro Terblanche identifying an opportunity: “we are small, but we know tech transfer”. Professor Terblanche assembled a “consortium” with Biovac and the South Africa Medical Research Council (SAMRC) to apply. This appealed to Dr Friede, who commented that the consortium, and its location, were “attractive”.   

Although Afrigen was announced in June 2021, Bio-Manguinhos in Brazil presented a proposal for ‘end-to-end’ mRNA manufacturing capacity transfer. Then head of vaccine innovation, Dr Sotiris Missailidis, reflected that the early impression given was that “the model was going to be a decentralised. Model” with several hubs, each with spokes.  

“What I didn’t know was that, at some stage, […] there was a decision taken from WHO or whoever, that as there was increasing political and financial pressure, many people wanted to come in. […] So the decision was taken to have on central hub and everybody else would be spokes.”  

The study authors convey a sense of confusion about the hub/spoke situation well into 2022. In 2024, the programme “continues to evolve”, encompassing a “diverse array of actors”. The fourteen LMIC-based “spokes” are now known as “partners” because of “negative connotations”.  

Quid pro quo 

The “first defining feature” of biopharmaceutical production relates to the “limited quid pro quo” that the public sector expects in return for supplying private actors with financing, R&D, and product leads. Weak conditionalities are often attached to government and philanthropic funding of biopharmaceutical R&D. 

“Conventional wisdom is to grant maximum discretion to recipients of public funding, including universities and government laboratories, as well as private actors about how to commercialise biopharmaceuticals.” 

From this, the authors infer that the state’s role is to subsidise, not shape, innovation. Funding for the mRNA programmes comes from governmental sources through MPP, which secured commitments from France, the European Commission, Germany, Norway, Belgium, and Canada, as well as the South African government and the African Union. The donors have committed US$117 million to the programme, which is expected to be “self-sustaining” by 2026. These funders have “shaped the programme in multiple ways”.  

For example, Germany reserved funding for a staff position at the hub, but the requirement for a French or German national meant that Afrigen was unable to fill the position. Canada, the second largest donor country, stipulated that its funding should be allocated to the Cape Town hub and four countries hosting manufacturers: Senegal, Nigeria, Kenya, and Bangladesh.  

“According to one interview participant, while HICs are supportive of transferring technology to LMICs, they would prefer that such transfers do not extend to the more upstream inputs into mRNA vaccine production, including novel LNPs and antigens.” 

A “critical question” for the authors is if the funding secured for the programme has been “leveraged into a shared set of commitments geared towards improving equitable access”. Relationships are defined by legal agreements drawn up by MPP, granting LMIC partners a “non-exclusive, royalty-free, non-sublicensable, non-transferable, irrevocable, fully paid-up, royalty-free license” to the technology and rights held by Afrigen and Biovac to “make, or have made, use, offer for sale, sell, have sold, export or import” in their respective territories and other LMICs. LMIC partners must grant MPP a global, non-exclusive, royalty-free license to “practice and have practiced the data and the Inventions for the purposes of fulfilling its mission” that is “non-transferable, but sub-licensable”.  

The “pooled, multilateral approach to knowledge production” is “rare” for the sector, which is attributed to the fact that MPP was in a “fundamentally different position”. However, the authors identify several “notable incongruities” in the legal architecture, with a risk of “fragmenting the larger, collective enterprise of improving equitable access”. For example, some partners have still not signed on, and an “unevenness” between LMIC partners and SAMRC-funded laboratories is “embedded in the programme”.  

Another feature of the programme’s funding implications is that MPP “stopped short” of requiring products to be priced affordable outside a public health emergency of international concern (PHEIC). As the pathogens targeted by various partners, such as TB and malaria, are not currently designated as PHEICs, the programme does not constrain pricing decisions. Instead, there is an “assumption” that the products brough to market will “of necessity, be affordable”, to ensure LMIC governments pay for them.  

On the other hand, SAMRC funded projects must ensure that “resulting products” are “available and accessible at an affordable price”. This enforceability of this expectation is called into question by a lack of experience.  

“The programme’s approach reduces the pursuit of equitable access to the task of fostering more localised production. This is a logical step towards addressing local population health needs. But localised access is never guaranteed.” 

Licensing limits 

Partnerships in the “dominant model” of biopharmaceutical production tend to “secret and transactional in nature”, with agreements shrouded with confidentiality conditions. More open arrangements are therefore “relatively uncommon”. At the time of applying to WHO, the consortium expected to receive technology transfer from an established mRNA manufacturer. However, they “didn’t even want to talk”, so the project became a “green fields vaccine innovation”. As the journey evolved, knowledge gaps emerged and were addressed, often with the “help of outsiders”. This was occasionally “coupled with a commitment to assist Afrigen or another consortium member in gaining internal capacity”. 

“Participating in the programme is a business opportunity.” 

The programme’s architects are “walking a fine line between trying to seed collaboration” and “trusting all involved to thread the commitments to IP access throughout that evolving web of relationships”.  

MPP as a “power broker” 

Another feature of the biopharmaceutical sector is the industry’s “highly financialised character”, evident in many firms’ decisions to become publicly traded or on stock exchanges. This has implications for the strategic direction of these firms and product prices. There is “no indication” that the mRNA programme mirrors the financialization of more established biopharmaceutical companies. However, MPP’s role as an intermediary “simultaneously adds value to, and imposes a drain upon”, the programme, which the authors suggest is “not the optimal way to provide technology transfer”.  

Some interviewees comment that MPP’s technology remote transfer group seems to be “micromanaging”, striving to “be in charge of everything”. If the programme fails, it would be “because of that kind of dynamic, not because the science doesn’t work”. Additionally, there is concern that MPP’s “presence and philosophy” may not work to the advantage of different participants in the programme, with one interviewee questioning why MPP and the Gates Foundation are not working together.  

Market-based governance 

The final feature of the “status quo” is that the direction of biopharmaceutical prodcution is “concentrated in the hands of powerful, private actors that are, at bottom, governed by the market”. Afrigen has directed its mRNA product development towards 11 potential diseases, with Professor Terblanche suggesting that priorities have not been shaped by the prospect of financial gains. She looks for the “unmet need”, but acknowledges that she may be “forced to prioritise”.  

The lack of pricing commitments in Afrigen’s Grant Agreement with MPP “could be interpreted as an incentive for Afrigen to commercialise its technology” or a suggestion that the architects “did not contemplate” Afrigen generating mRNA products of its own. The potential for Afrigen to “yield to market forces” is recognised by the architects. 

“The near inevitability of Afrigen’s exit in the eyes of those who designed the programme speaks to an underlying failure of imagination concerning how the mNRA programme is governed.”  

The privatised governance strategy “preserves the programme architects’ control”. Indeed, the governance structure excludes “direct representation from LMIC governments”. These choices “reflect the programme’s alignment with the dominant, market-driven approach” of biopharmaceutical production.  

Sticking with the status quo? 

The authors find that the programme “does not substantially depart from” at least three of the four identified “status quo” features. They conclude that to “realise technology’s emancipatory potential”, more attention should be directed to “social context and structural challenges”. Their analysis shows that “the needs and perspectives of LMICs are not sufficiently centred in the programme” and that the programme works within the existing biopharmaceutical production system without relinquishing architects’ control.  

“There is a significant risk that the programme, which is claimed by WHO and MPP as a collective effort to improve manufacturing capacity in LMICs for LMICs, will not solve the problem of equitable access to biopharmaceutical innovation.”  

Do you agree with the concerns raised by the authors in the study? How can they be addressed quickly and effectively in the current context, or would you expect to see lessons learnt in preparation for future efforts? To share your perspectives on initiatives to improve access to essential vaccine technologies, join us at the Congress in Barcelona next month, where we look forward to welcoming Professor Terblanche among experts on the subject. Don’t forget to subscribe to our weekly newsletters for more vaccine news.