Dear Readers,

We are very pleased to present our research report for this quarter: Beyond the Breakthrough: The Uneven Geography of mRNA Vaccine Production.

My colleague Vivek has put together this timely analysis, taking stock of the challenges and opportunities for mRNA technology in the developing world. Also find an exclusive interview with Petro Terblanche, CEO, Afrigen Biologics & Vaccines.

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GHF Plus: Global Health Policy Intelligence

Beyond the Breakthrough: The Uneven Geography of mRNA Vaccine Production

By Vivek N D

Priti Patnaik contributed to this report

Vivek N.D., is adjunct faculty, School of Legal Studies and Governance, Vidyashilp University, Bangalore, India. E-mail: viveknenmini@gmail.com

1. Introduction: Between Promise and Power

In August 2025, U.S. Health Secretary Robert F. Kennedy Jr.—a known vaccine sceptic—announced plans to cancel $500 million in US Department of Health and Human Services (HHS) funding for mRNA vaccine research targeting viruses such as influenza and COVID-19, a move widely condemned by health experts for undermining scientific progress and public trust.

Few scientific revolutions have been as rapid and transformative as the emergence of messenger ribonucleic acid (mRNA) technology. Within a year of the SARS-CoV-2 genome being sequenced, mRNA vaccines from BioNTech–Pfizer and Moderna had rewritten the timeline of vaccine development. The global admiration for this triumph of biotechnology was, however, tempered by a hauntingly familiar inequity: while doses flowed freely in the Global North, much of the Global South watched and waited. Tedros Adhanom Ghebreyesus, director-general of the World Health Organization (WHO), acknowledged this as a “catastrophic moral failure.”

The pandemic revealed that innovation without access is a hollow victory. Vaccine nationalism, patent monopolies, and export controls turned a scientific miracle into a political crisis. It was this reality that led to the creation of the mRNA Technology Transfer Programme (mRNA-TTP) in 2021 — a flagship initiative to build sustainable, regional production capacity for mRNA vaccines and therapeutics in low- and middle-income countries (LMICs). Administered by the WHO and the Medicines Patent Pool (MPP), the hub, based at Afrigen Biologics and Vaccines in South Africa, was envisioned as a node of learning, replication, and empowerment.

Yet, four years on, the question remains whether this technological diplomacy can truly disrupt the entrenched geopolitical hierarchies of global health. The mRNA-TT program is at once a promise of scientific sovereignty and a mirror reflecting the enduring coloniality of pharmaceutical power.

2. Achievements and Aspirations: The mRNA Technology Transfer Programme

The mRNA-TTP was conceived as an audacious response to vaccine inequity. Anchored at Afrigen and supported by the South African Medical Research Council (SAMRC) and Biovac, it now links 15 partner manufacturers across four continents, forming a network of shared innovation. As of 2025, these include Biovac (South Africa), Biological E (India), Serum Institute of India, BioManguinhos (Brazil), Sinergium (Argentina), Incepta (Bangladesh), BioPharma (Indonesia), and Institut Torlak (Serbia), among others. The Programme has made a strategic shift from a focus on COVID-19 vaccines to an expansive mandate that includes influenza, dengue, HIV, and even monoclonal antibodies for LMIC-specific diseases.

Its integration into WHO’s Health Technology Access Programme (HTAP) in 2024 has aligned technology transfer on vaccines with the broader goals of pandemic preparedness and health security. The Programme’s Phase 2.0 (2026–2030), launched in Brussels in October 2025, envisions the creation of self-sustaining manufacturing ecosystems in at least 10 LMICs capable of producing up to 1.9 billion pandemic-ready doses by 2030.

These achievements and aspirations are significant. Afrigen, in particular, has demonstrated that reverse engineering can serve as resistance: it successfully replicated Moderna’s mRNA-1273 vaccine sequence using publicly available data, defying the narrative that sophisticated biotechnology cannot be locally mastered. Yet, while the architecture of capacity has grown, its outputs remain limited. Not one LMIC partner has yet commercialized an mRNA vaccine. The Programme, then, stands at a delicate midpoint — symbolically emancipatory but materially incomplete.

Yet, it is a model that must work for the future.

In response to queries from Geneva Health Files, a WHO spokesperson said:

“Sustainable mRNA capacity will be driven by a pipeline of products that are required on a routine basis, as this generates regular demand. This is one of the key elements which is being addressed by the Phase 2.0 of the mRNA TTP.

There are number of financing models and elements which are relevant, recognizing that it will take time to generate the pipeline of mRNA vaccines and therapeutics that will drive long term sustainability and manufacturing capacity retention. Public private partnerships and blended finance approaches, including development bank loans and other debt and equity-based instruments, are important as they offer affordable financing solutions to ensure that capacity can be generated and retained. Advance market commitments provide the longer-term market assurance that manufacturers require, and non-refundable or grant-based instruments can support product development in particular, providing the necessary funding to advance product candidates and move them towards early-stage clinical trials. In addition, evergreen or revolving funds provide a key mechanism for supporting both interpandemic sustainability and the necessary scale-up of manufacturing capacity during outbreak situations. This recognizes that manufacturers alone are not in a position to bear all the risks and financial burdens associated with expanding capacity in a pandemic situation.”

In a comprehensive interview for this story, Petro Terblanche, CEO of Afrigen, calls for a portfolio approach with late stage, early-stage candidates and but also to prioritize products for which the market is uncertain but the need is great. “Because nobody else is going to fund that, but where the burden of disease requires a product. That’s what we would try,” she says. (Read full interview below)

3. The View from the Ground: Manufacturers and Their Markets

If the mRNA-TT Programme embodies a new vision of equitable innovation, its translation into practice depends on the realities faced by its manufacturing partners. Across Africa, Asia, and Latin America, the narrative oscillates between cautious optimism and sobering realism.

In South Africa, Biovac and Afrigen have become continental beacons. Their participation in WHO’s network has transformed local infrastructure, training hundreds of bioengineers and achieving partial GMP certification. However, both firms still rely on imported active pharmaceutical ingredients (APIs) especially from India and China, and thus are subject to the impact of potential third-country tariffs from the United States. This dependence exposes the brittle foundation beneath claims of “vaccine sovereignty.”

India’s Biological E and Gennova Biopharmaceuticals present contrasting models. Gennova’s Gemcovac-19, developed with mRNA technology fully indigenized in Pune, became India’s first homegrown mRNA vaccine to receive domestic regulatory approval in 2023. Yet, despite its scientific success, global diffusion has been limited by lack of WHO prequalification — a reminder that sovereignty is contingent upon recognition from international regulatory authorities.

In Brazil and Argentina, the story is one of institutional ambition tempered by economic constraint. BioManguinhos has leveraged partnerships with the Pan American Health Organization (PAHO) to advance mRNA influenza vaccines against H5N1, while Sinergium Biotech has piloted end-to-end process training with support from Afrigen. Despite its potential to advance regional health sovereignty, the program’s success remains tied to ongoing donor and governmental investment. Similarly, BioPharma Indonesia has focused on hybrid funding models involving state co-investment, positioning itself as a regional anchor for Southeast Asia.

In response to queries from Geneva Health Files, Matthew Herder, Associate Director, Health Justice Institute, Schulich School of Law, & Professor, Department of Pharmacology, Faculty of Medicine, Dalhousie University at Nova Scotia, said: “In my view, there is no obvious financing model available to entities in LMICs for production at the scale unless they are state controlled enterprises with access to stable and significant government funding. Within the mRNA Programme, Brazil’s Bio-Manguinhos and Indonesia’s PT BioFarma are the potentially the only two organizations that might have access to such funding from what I can discern. Lacking that kind of government funding and support, other entities in the mRNA programme are likely better off targeting smaller scale production for outbreaks (as opposed to epidemics and pandemics) and I believe that entities like Afrigen have already moved in this direction.”

Herder further pointed out, “If, however, mRNA vaccine producers are working towards manufacturing on a community kind of scale (as opposed to production for whole populations) they should in theory be able to pivot efficiently. This assumes that they have GMP-grade facility in hand and established relationships with organizations that fund and run clinical trials. It’s important to note, though, that clinical trials is one of the real strengths of South Africa’s scientific community.”

In Africa, BioNTech’s announcement in 2024 of up to $145 million in Coalition for Epidemic Preparedness Innovations (CEPI)-backed funding to build modular “BioNTainers” — prefabricated mRNA facilities in Rwanda, Senegal, and South Africa — symbolizes a dual reality. On one hand, it offers a tangible boost to regional production capacity. On the other, it raises a political question: does such philanthro-industrial investment empower local autonomy or simply rebrand dependency under a new corporate idiom?

Beyond the mRNA-TT network, China’s relative late entry into mRNA development, underscores the geopolitical contest over narrative ownership. Despite lagging behind Western frontrunners, Chinese firms like Walvax and Abogen are now scaling domestic platforms, signaling a multipolar race for biotech sovereignty.

4. Beyond Transfer: The Unfinished Project of Decolonizing Global Health

The mRNA-TTP occupies an ideological frontier. It challenges the colonial architecture of global health by proposing a model of distributed innovation — but it remains constrained by the very systems it seeks to transcend.

In a comprehensive examination of the programme, published in September 2024, Herder and co-author Ximena Benavides highlighted that despite its promise to build vaccine self-sufficiency, the WHO–MPP mRNA TTP largely reproduces existing power asymmetries in global health governance, limiting LMIC manufacturers’ autonomy to produce affordable, locally relevant mRNA vaccines.

· The first and most stubborn barrier is intellectual property (IP).

Mechanisms like licensing and open-access models are needed to prevent IP on lipid nanoparticle delivery systems from hindering mRNA vaccine production in LMICs.

As Médecins Sans Frontières (Doctors Without Borders) warned, without access to know-how for lipid nanoparticles (LNP) and stabilizing enzymes, LMIC manufacturers are left assembling fragments of a technology they do not own. Even WHO’s voluntary framework cannot compel originator companies to share proprietary data, leaving the network dependent on reverse engineering rather than genuine transfer.

According to Herder, mechanisms (licensing, technology transfer hubs, open-access models) to help ensure equitable mRNA IP access might not help – “The short answer is that there are no guarantees that any of those mechanisms will work. Lipid nanoparticle technology is an especially IP-intensive area and to date, the dominant players have shown little interest in sharing their technology with entities in the Global South. On the positive side, I am aware of at least one example of an LNP patent-holder licensing its rights to an LMIC entity. That case involved Genevant (a Vancouver based company) and the Chula Vaccine Research Center in Bangkok, Thailand. However, the license still took four months to negotiate. Whether other researchers and organizations based in high-income countries with IP portfolios will similarly step remains to be seen. For the time being, many of the entities that have IP around LNPs are busy suing one another in the courts in the US, UK and Canada. When the dust finally settles on that litigation, I would hope the litigation doesn’t shift to the global South.”

He further stated, “In the past couple of years, access to LNPs has been a significant issue and for that reason there has been some discussion of creating an ‘LNP consortium’ that would act as a kind of clearinghouse for IP rights that stand in the way of using various LNPs. I’m not sure that any real progress has been made towards creating such a consortium. Another key bottleneck is plasmid Deoxyribonucleic Acid (pDNA). For most mRNA producers, access to pDNA is crucial; it’s essentially the first key input into the whole mRNA manufacturing process. So, if you don’t have the capacity to make GMP-grade pDNA or can’t easily access it, then it is very hard to become an independent mRNA producer. You’re at the mercy of your supplier if and when the next public health emergency arises. So, to the extent LMIC producers can build their own capacity to produce pDNA, they will be much better off the next time around.”

On IP, WHO said, “To minimize the risk of intellectual property becoming a barrier — the mRNA TTP takes a proactive, multi-pronged approach: Patent landscape analyses are conducted to identify relevant IP on technologies; Freedom to operate (FTO) assessments are funded for partners; When potentially blocking IP is identified, we explore dual strategies: either working with partners to design around the protected technology or pursuing voluntary licences where needed. This approach supports both compliance and innovation, while keeping pathways open for LMIC manufacturers to develop and produce mRNA vaccines at scale.”

(See more on IP in Terblanche interview below)

· The second barrier is regulatory systems.

While regional bodies like the AMA and PAHO are attempting to streamline processes, the lack of harmonized pharmacovigilance and quality control systems continues to impede market authorization. Without WHO prequalification, locally made vaccines cannot enter global procurement channels such as COVAX or UNICEF — creating a paradox where LMICs build factories but cannot sell their products internationally.

Across diverse geographies, a common refrain emerges: the future of mRNA technology will depend less on technical capacity and more on the construction of coherent markets, harmonized regulation, and genuine technology ownership. The WHO’s African Medicines Agency (AMA), operational since 2021, offers hope of regional regulatory alignment, yet progress remains uneven. With just eight of 54 African nations reaching WHO Maturity Level 3 (signifying a stable and effective regulatory environment), regulatory weakness continues to undercut the readiness the mRNA-TT program seeks to achieve.

· Third, chronic underinvestment undermines sustainability.

Realizing Good Manufacturing Practices (GMP) compliance for all sites under the mRNA-TT program and sustaining research on 12 mRNA candidates will demand an additional US$200 million—funding that remains uncertain.

Donor fatigue and shifting global priorities threaten to derail this trajectory. The Institute for Health Metrics and Evaluation reported that Developmental Assistance for Health (DAH) declined sharply in 2025 to $39.1 billion—down over 20% from 2024 and to its lowest level in 15 years, now less than half of what it was at the height of the pandemic in 2021. Sub-Saharan Africa—the region receiving the largest share of global DAH—is projected to face the steepest reductions, with funding expected to fall by 25% ($4.6 billion) between 2024 and 2025 and a further 6.6% ($0.9 billion) decline by 2030.

On sustainability, WHO spokesperson said:

“Significant efforts are being made by a number of organizations, including but not limited to WHO, CEPI and Regional Vaccine Manufacturing Collaborative, to develop and support robust and resilient supply chains across vaccine platforms, including mRNA. This work includes consideration of regional initiatives which also aim to reduce supply bottlenecks, including Platform for Harmonised African Health Manufacturing (PHAHM) in Africa and ASEAN Vaccine Security and Self-Reliance (AVSSR) in Southeast Asia.

Within the programme WHO/MPP has supported engagement between manufacturers and Multilateral Development Banks/Development Finance Institutions on discussions related to potential financing mechanisms and funding instruments that cater to the varied needs of the partners which range from newly established manufacturers to established manufacturers that already supply vaccines for national/regional immunization programs.”

WHO also stated, “Potential bottlenecks specific to mRNA vaccines includes in particular nucleotides and modified nucleotides, enzymes including RNA polymerase, capping reagents, and ionizable lipids and other lipid nanoparticle components. Therefore, efforts to diversify suppliers of these reagents and consumables are of vital importance, also noting that these suppliers themselves will have to ensure scalability as they need to be able to operate and remain commercially competitive at interpandemic production levels and have the ability to be able to scale up production in outbreak situations, therefore they need to address the same scale up dynamics as the mRNA vaccine manufacturers themselves. Cold storage facilities also need to be developed and maintained on a regional and national basis. Development of mRNA products that are stable at 2-8°C, with associated reduction in the need for -80°C and -20°C storage, will reduce the cold storage issue but sufficient refrigeration capacity across the supply chain, including regional and national distribution centers, will still be required.

Development of an expanded network of regional suppliers of key mRNA components reduces the risk associated with reliance on global suppliers, however establishing and expanding these regional providers of key raw materials requires development of strong business cases to justify the investment required in setting up such regional hubs, and achievement of the necessary quality and reliability standards.”

Sustainability and funding remain big concerns for Afrigen.

Terblanche said, “Over the next seven years, if this program (all 16 partners) can raise a billion dollars and of course that has to be diverse funding, it can’t just be grants, it has to be a combination of equity, debt, commercial returns and innovative funding models…. I think for a billion dollars this program can develop a pipeline of life changing vaccines and therapeutics and narrow the pipeline and take five products into licensure.”

Specifically, Terblanche explains, for a greenfield project, “to build a facility end-to-end, build the platform, validate the platform, without any product. You are going to need and it’s a very modest amount compared to leading mRNA companies because we’ve localized, you are going to need $50 million. Now, what do you need now to sustain at least a platform for pandemic preparedness? In our case, because we are small, modular, we’ve been integrated. We’ve really developed a resourceful kind of entity. You would need a baseline of about $4 million per year to sustain the pandemic readiness.”

Finally, import-based procurement remains the silent killer of local industry. Global health procurement — dominated by Gavi, UNICEF, and Western suppliers — continues to favor established multinational manufacturers under the logic of “risk minimization.” Even where LMIC producers achieve quality parity, they face exclusion from tenders due to lack of track record.

In October 2024, Aspen Pharmacare’s Stavros Nicolaou, attributed Africa’s unrealized manufacturing potential to regulatory bottlenecks and restrictive procurement policies, warning that without a fundamental restructuring of procurement practices, the much-touted “local manufacturing revolution” risks remaining little more than rhetoric. Nicolaou is Aspen’s senior executive for strategic trade and chair of the Pharmaceutical Manufacturers Association of South Africa.

5. Between Rhetoric and Reality: The Political Economy of Sovereignty

The question that now confronts the global health community is whether the mRNA-TT program and its allied initiatives represent a genuine decolonization of biotechnology or merely a reconfiguration of dependency.

The mRNA-TT Phase 2.0’s ambition to produce 1.9 billion doses is laudable, but the geopolitical ecosystem within which it operates remains dominated by straitjacketed financing and IP structures controlled by entities in the developed world. The BioNTech–CEPI partnership, while ostensibly supportive, positions Africa as a manufacturing base for European technology — echoing colonial production chains where extraction replaced exchange. Similarly, despite domestic innovations like Gemcovac-19 in India, international recognition and market entry remain controlled by Western regulatory norms.

This asymmetry is compounded by the politics of narrative. The post-COVID “vaccine nationalism” can be seen to have mutated into “biotech nationalism,” where nations frame vaccine production as a marker of sovereignty, often for domestic political capital rather than structural transformation. The risk is that symbolic breakthroughs — new labs, ribbon cuttings, and modular plants — are mistaken for systemic change.

Yet it would be reductive to dismiss the mRNA-TT programme as performative. Its collaborative structure, open-source ethos, and civil-society oversight represent a nascent counter-hegemonic experiment within global health governance.

In the wake of the COVID-19 pandemic, two base-modified mRNA vaccines encoding the SARS-CoV-2 spike protein were developed at unprecedented speed, transforming the landscape of global biomedicine. This breakthrough was made possible by the pioneering work of Katalin Karikó and Drew Weissman, whose discoveries on nucleoside base modifications in mRNA earned them the 2023 Nobel Prize in Physiology or Medicine. Yet, beyond the scientific triumph and the billions in profit amassed by BioNTech–Pfizer and Moderna, the true value of mRNA technology lies in its potential to democratize access to life-saving vaccines. That promise, however, remains unfulfilled, as enduring inequities in vaccine distribution and technological ownership continue to define the contours of global health injustice.

Thus, what is missing, is a more robust institutional mechanism to translate moral intent into material equity. Without binding commitments on IP sharing, regional financing, and equitable procurement, the mRNA-TT programme risks reproducing the inequities it seeks to dismantle. The deeper challenge is not merely to transfer technology, but to transform the terms of production that currently underpin global health.

6. Conclusion: Toward a New Cartography of Capacity

The history of global health has long oscillated between aspiration and asymmetry. The mRNA TTP stands as one of the most ambitious attempts to rewrite that history — to transform sites of consumption into sites of production, and dependency into capability. Its achievements — from Afrigen’s reverse engineering to the expansion of mRNA research across 15 partners — are undeniable. Yet, they also illuminate the structural inertia of a system where access is conditional, and sovereignty remains aspirational.

For now, local manufacturing remains a challenge. The WHO–MPP network has planted the seeds of change, but the soil of global governance is still hostile to genuine autonomy. The next five years — the life of Phase 2.0 — will determine whether this experiment matures into a model of equity or fades into the archive of well-intentioned failures.

To realize its promise, the mRNA-TT programme must move beyond partnerships, and toward substantive redistribution: of knowledge, of financing, of regulatory power. Only then can it escape the gravitational pull of geopolitics and embody what it proclaims — a decolonized, sustainable, and self-reliant architecture of health innovation.

The challenge, in essence, is not scientific. It is political — the unfinished struggle for sovereignty in a world where life itself remains stratified by patent and power.

Terblanche refers to the mRNA program as the biggest tech transfer program in the history of all medical technology. She says that in 2020-21 none of the companies in the program had mRNA capability. By 2030, 10 will have GMP facilities and a capability to respond utilizing mRNA.

Queries sent to the MPP were not answered by the time this report went to print.

THE GENEVA HEALTH FILES INTERVIEW:

PETRO TERBLANCHE, CEO, AFRIGEN BIOLOGICS AND VACCINES

By Priti Patnaik

Bianca Carvalho contributed to the production of this interview.

Q1. Geneva Health Files (GHF): What have been some of the lessons, the wins, and the challenges in this process for mRNA producers across the world?

Petro Terblanche (PT):

I assume you know the background of the mRNA tech transfer program. You know how it came about….we didn’t receive a tech transfer. So, this became the greenfield project driven by the quest for health security for LMIC partners. And the reason why we continued in 2021, despite the fact that we couldn’t get a tech transfer, was because it is still recognized as one of the very important platforms, mRNA for pandemic and epidemic preparedness and outbreak response.

In addition to that, mRNA has diverse applications. So, the thinking, certainly from the mRNA tech transfer program leads and partners, is that this is a future relevant platform. This is a platform that has the ability to prepare LMICs for pandemic preparedness, but it also has the potential to sustain companies interpandemic, provided that we deal with some of the challenges. And I think the challenges for us in the program changed as we evolved.

So, the first challenge was, you don’t get a tech transfer. Okay, now we have to develop a technology. None of us even worked with mRNA. We have highly specialized, qualified scientists, but they’ve never had it in their hands. mRNA was never there. First challenge, what is the way you do? We have great academic institution partners that has some mRNA capabilities, and you fast track, you learn, you listen, you read, you experiment, you fail, you experiment…..

So, as we then built the platform, the next challenge was the pandemic has moved on. We have developed a platform, and we can only validate this platform with a product that has data. So, it has to be a COVID-19 vaccine that has data, because we need to compare and we need to know whether the platform that we build here brings safety and efficacy data before we transfer it.

So, the next problem was: we can’t do a clinical trial. Firstly, it was because we can’t get a reference product. We couldn’t get access to the BioNTech and the Moderna vaccines for a Wuhan strain vaccine as it was not recommended for use anymore. We couldn’t get permission to do comparisons in non-inferiority studies.

And then suddenly we were at the point where, at least in South Africa, there’s no vaccinations anymore, and you sit with a population that has been 100% exposed. It is a very difficult clinical trial to do, and do you want to spend so much money and expose patients to a new experimental drug, even though you have great preclinical safety data, and if there’s no public health benefit? These were the challenges as we evolved.

And then we made a decision guided by the mRNA TT Programme Steering Committee, well, we don’t need to do a clinical trial to validate the platform. And it was extensive work then done, multiple pre-clinical studies including non-human primates, not necessary for a COVID-19 vaccine, but necessary to validate the platform.

Once we validated the platform, we have to start transferring to partners. The next challenge was: in the early days of the programme none of the partners had facilities that are ready to receive mRNA technology. We can’t train and transfer technology in a vacuum. A significant part of the programme was the MPP team performing the partner readiness assessments and gap analysis to that once we have done onsite transfer technology, the people can go back to their laboratories and demonstrate the technology.

The leading implementing partners were Sinergium in Argentina as they hit the ground running. Strong partners in the network were Bio-Manguinhos, PT BioFarma, Incepta and Biovac who has great technology absorption capabilities. So, we were able to bring the very experienced vaccine manufacturers that have knowledge of tech transfer and knowledge of vaccines first on board and transfer. And we’ve now done 13 of them.

Some of the challenges are - Africa manufacturing partners that don’t even have a facility. So, what do you do now? This is a challenge and a commitment to build capacity. The innovative solution is to work with academic/public private partnerships in the Countries such as for example, Kenya BioVax Institute and KEMRI (Kenya Medical Research Institute). Afrigen transfer the knowledge to KEMRI and start fostering a knowledge platform and facilitate collaboration between an academic institution and a new startup entity, which is good, because that also now allows us to build a pipeline of new products..

Another challenge was Freedom To Operate. We have to be very clear on what we do here, we perform research and development under the Bolar Exemption, but we can’t take a product through to market unless we have the freedom to operate and not infringe IP. Our strategy to ensure FTO, was to create partnerships with companies that are willing to develop with us and to license their technologies to us, such as some of our collaborations with the owners of LNPs – an essential component of producing the mRNA final product. In addition to FTO for the lipids, we are also using the opportunity to explore lipid combinations that will solve the problem of better thermostability, because that’s a challenge.

And I must tell you, if you ask me, how did your team overcome all your challenges, or what was the one word that you would share that was the enabler for us to overcome our challenges? It is one word: partnerships. Collaboration. So, we then choose companies with lipids that give the thermostability, but are prepared to license on reasonable terms for low-middle income countries without losing the value of what they’ve developed. I mean, this is a unique model. So, we master that challenge. Then we went back to the UTRs (Untranslated Region Sequences). Moderna owns the IP on these UTRs, they are very valuable. How do we replace it? So, we partner with Yale University, and Yale gives us a license. So, then the freedom to operate challenges became more palatable, and we can move forward.

Then the next challenge is: what are you going to make in this facility? Now you have a big challenge, firstly to obtain a GMP (Good Manufacturing Practices) license and secondly to ensure we have products to manufacture. Build the facility, build a platform, get a GMP license, develop new products. So, we are the first applicant. Never before an investigational new drug was taken from the lab to the clinic in South Africa. So, we are pioneering that. Thirdly, our SAHPRA inspectorate (South African Health Products Regulatory Authority), National Regulatory Authority, which is really great, but never in South Africa, inspected an mRNA end-to-end facility because it doesn’t exist yet. From R&D to internal technology transfer to CMC (Chemistry, Manufacturing, and Controls). So, we pioneered this, and here we are now, we have completed our GMP audit, and we are closing out. We have < 20 findings in total. So, this challenge we will beat.

Now the next challenge, close out, get your license. Then the challenge: Now we have a GMP facility. We have mastered the mRNA platform. We have products and development. What are we going to make? How do we keep these facilities running? How do we keep our people? How do we ensure we sustain the platform? How do we move our products to the clinic?

Where do you get funding to do that? And now this is where we are now. Our biggest single, biggest challenge is: how do we protect the platform, which is for pandemic preparedness and epidemic preparedness, because we even include the ability to stockpile in our license. The ability to stockpile for biosecurity and for health security purposes.

Who’s going to recognize how important this platform is for Africa, South Africa, and fund our baseline? How are we going to get funding between the shareholders and grant funding to develop products, to address the burden of disease for which there is not a clear market value – just a huge health benefit. We have prioritized High Burden Disease, diseases for which there is no market. There’s a market, but there’s no profit, they are neglected. So how do we source funding so that we can develop these vaccines and therapeutics for diseases for which the business plan doesn’t bank. The only way you can do that is through public, private partnerships with support. So, this is our single biggest challenge today.

I have three of them.

First, funding. How do we keep this going? Number two is, how do I keep my people, and how do I safeguard them and keep them, give them the future that they deserve? Thirdly, how do we make sure that we deliver on the promise that we’ve made for every partner, every funder and every collaborator?. And how do we get a health care product into the clinic? And I think as we now evolve, as we get to a phase one, the challenge will be, well, how do we make sure that we have funding to take the product through development and into registration. So, it will evolve. I think that’s the bottom line. The challenges will evolve…

Q2. GHF: How can LMIC producers address IP challenges?

PT:

It’s complex, Priti. It is dynamic. It is evolving. Whereas four years ago, we didn’t have filings in many low-middle income countries, that whole IP protection behavior has changed in the innovator companies. How do we get an organization that has IP, that gives us freedom to operate, to be willing to partner with us. And I can tell you, in the last six months alone, I myself, had several discussions with the owners of the lipid nanoparticles and there was one particular company that was absolutely not even respectful. They said: “We want a million dollars up front; we want the next million dollars there”. I said, this is a development project, we’re in pre-clinical phase. They said: “this is our piece. This is what you pay”. And that was very hard. I mean, there was absolutely no orientation towards joint development I said, we will pay your royalties on successful registration. I can’t pay your upfront fee because the value is not yet fully developed, but we ready to pay your royalties as long as it is reasonable. And they said: “We want immediate payment”.

So, then we get another company which is smaller, more or less unknown, and we say to them: “can we collaborate? We’ll test your lipids in our products; we’ll share the data with you”. I think we have now 12 or 13 months of stability data. “If the data is good, will you license it to us?”

And we found two companies prepared to do that. So, for freedom to operate, you have to have the like mindedness also. But that took us two, three years, because we tried this one, and then that one, etc. And now we have that, we have a partner that we can move forward. So, for our partners, we are saying to them, we connect you with Company X. We will facilitate the discussion, but because Company X will license to Afrigen, they may not necessarily want to license to the whole network. Because it’s complex. It’s a very complex model.

MPP, of course, has a history in voluntary licensing, and it has done it very well, but an LNP (lipid nanoparticle), which is a component of a vaccine, is a difficult model. So, I think there’s two models for us. Some companies may license to MPP and enable the network. Others just go bilateral with different partners. And I think we should allow these dynamic models to proceed and to exist.

Q3. GHF: There is some level of shared innovation across the network already, right?

PT:

Yes. So, the mRNA COVID-19 vaccine used to validate the platform is licensed, royalty free from Afrigen to MPP, royalty free to the network, and we continuously exchange information and learning. I can tell you, Priti today, we have POLYVAC from Vietnam, in our laboratories for their mRNA transfer and training and we share openly and freely. So, there’s a lot of sharing and openness in the network, a lot of it - making the mRNA TT Programme a unique model for technology transfer and innovation.

Q4. GHF: Is the model actually workable in the future? What about readiness of partners?

PT:

I think it’s a model that can be replicated. And I have different minds around how you manage it. If you have such a complex, multilateral tech transfer, you need a central body to coordinate and manage that. And that central body can be the giver of the technology, or it can be an independent, and in this case, it was independent – WHO with MPP. Because it is a complex model to manage. While we are developing the tech, collectively and through teamwork we have to do the readiness assessments for all the partners, we need to prepare the partners, we need to then transfer, then we need the partners to demonstrate the technology, and then we scale up.

So, I think this is a very ambitious program, but it is the biggest tech transfer program in the history of all medical technology. So, it has to work. And I think part of the reason is the impact…where we go from in 2020-21 none of these 16 entities, including Afrigen had any mRNA capability. In 2030, 10 will have GMP facilities and a capability to respond utilizing mRNA.

I think the other part of the program is the fact that very early on we said: “we can’t just transfer tech. What do we make? What are the products?” The fact that we, early on, we said we need a product, right? And now the whole program says we need products. And now the mRNA tech transfer program, mRNA 2.0 that was launched two weeks ago, it’s actually becoming a product development partnership. We need to develop products. It’s a product development partnership, because these manufacturers need products to be manufactured. So, I think this program, again, has evolved as a sustainability drive with a good deal of reality.

Q5. GHF: On the specific challenges LMIC producers should keep in mind and how to prepare themselves to address these hurdles?

PT:

So, we have with our 15 partners in 15 countries, apart from just building the technology and transferring it, taken an ecosystem approach. We share suppliers, we share knowledge and procedures on cold chain logistics and supply chains, we are sharing costs management practices across the value chain, we are sharing qualifications of material so that every partner doesn’t have to repeat the same efforts and challenges. So, this is much more than just technology transfer. It’s a bit of an ecosystem enabler lens.

And I have to tell you, that’s not in Afrigen’s brief. It’s not in our scope of funding, but we do that because we understand what we’ve learned here in an ecosystem, in a very fragmented regulatory system, and South Africa some of the better ones. And I tell you; our regulatory system is fragmented. It is challenging, all of that learning and all of the suppliers that we can rely on, we share with our partners, and it’s good for the suppliers because their markets are expanded. It’s good for us and our partners because we know we have a loyal supplier.

So, our challenge is waiting 18 months for equipment, waiting three months for raw material. If I was in Boston, I would get it in 24 hours. We are now working through which of our suppliers that we’ve qualified for GMP, are the ones that will prioritize us are loyal to us, and that operate not only as a supplier, but actually as a partner, and that we share with all the countries.

And the other thing is, the ecosystems of regulatory standards and compliance in some of our partner countries need to be developed. And actually, this program with WHO is training the NRAs in a number of the 15 countries to prepare them also to be able to onboard and understand this technology. So, there are so many components of this program that people don’t see.

Q6. GHF: On regulatory standards. Is that a hurdle for LMIC producers?

PT:

If you look again at the 15 partners, they’re all very different, they are diverse, and they are in different environments. If you, for example, look at Sinergium, Argentina has a ML3 NRA. If you look at Egypt, ML3, look at South Africa, ML3. But in the rest of the African countries, their NRAs are not ML3, for vaccines yet. So national regulatory authorities can’t inspect those facilities without ML3. So, this is part of the journey for Africa. But if you now go to Bangladesh, they just got ML3 again for vaccines. Indonesia, good. Other partners’ NRAs are still on a journey to meet the standard for safety and efficacy of vaccines.

So, for us to sustain this network, we have to make sure that the NRAs in those countries are at the level where we require it to be. South Africa, for example, for Afrigen we were inspected by SAHPRA, 22c which is a PIC/S guideline, and a WHO guideline. [Pharmaceutical Inspection Co-operation Scheme (PIC/S].

These are stringent regulatory requirements. And the technology that Afrigen is transferring to our partners, with GMP has to be compliant with these requirements. The facility that’s been designed here that we shared, we know we share this design of our facility. We share the process flow and the equipment flow that is, according to PIC/S, SAHPRA and WHO guidelines. And I think that must be non-negotiable. We cannot lower standards in this network. It has to be absolutely trusted. The products being developed by the NRA and tech transfer program are safe, effective and have not compromised public safety. I think it’s critical.

Q7. GHF: On the vagaries of access to inputs, LMIC producers will face reshoring and reshaping of supply chains in the context of tariff wars. We have biotech nationalism, so there are challenges LMIC will face in getting ahead of the queue.

PT:

You’re absolutely right. There’s acute awareness. So, what is happening in South Africa, and in Africa’s case, Africa CDC, in Latin America, and Southeast Asia, other entities, are now to work with suppliers to ensure the capacity is also decentralized. So, it’s interesting. ThermoFisher now has a facility in Africa. Merck is expanding capacity and others looking at partnerships even in South Africa, to have some of their manufacturing facilities. However, you have to retain the sustainability and the bankability of these expansions. But there is a decentralization happening in the key supply chains. And in the mRNA program, we are funding one or two, not us, WHO and MPP, startup companies that develop new enzyme platforms to supply mRNA. So, there’s little bits and pieces on how we slowly move towards what we need to have, we need to have security, right, without having an unsustainable business model, because every country can’t make syringes….

Q8. GHF: What are the kinds of financing models for LMICs. What is the cost estimate of getting something off the ground, and how much time will it take?

PT:

So, if you now have to go to greenfield, you may have to start all over, like with Afrigen again and build this facility end-to-end, build the platform, validate the platform, without any product. You are going to need and it’s a very modest amount compared to leading mRNA companies because we’ve localized, you are going to need $50 million. Now, what do you need now to sustain at least a platform for pandemic preparedness? In our case, because we are small, modular, we’ve been integrated. We’ve really developed a resourceful kind of entity. You would need a baseline of about $4 million per year to sustain the pandemic readiness.

Then now to drive products through to development is on a product specific basis. So, imagine if the network says we identify five products. Two mRNA therapeutics, one vaccine, one CAR-T and one monoclonal - a diverse portfolio. You will need a billion dollars over the next seven years, and it will have to come from different funders. I’m talking about products from development right through to licensure. And because you want to say we will at least want five products in the market for the network to sustain them, you have to probably start developing 20 because you’re going to have natural attrition. They fail. And that, I think that could be done with a billion dollars, which may sound like a lot of money, but if I think about how much we spend…. Of course, that funding should be a combination of grant government support and the company’s support, the company’s contributions. An organization, which I think was really fantastic for us, is CEPI, it is the only one that funds us to a phase one, and we are now prioritizing Rift Valley fever (RVF), because that is such an important pathogen. But we need that kind of funding, which says we will fund you through development, right through to at least phase one where you demonstrate safety and efficacy and you have a prototype vaccine that you could stockpile, put on the shelf for an outbreak. That’s the one component. The other component…we want to have therapeutics for adenocarcinoma of the lung or for colorectal cancer or pancreatic cancer, because these burdens of disease have global impact.

All the 15 countries have adenocarcinoma, solid tumours in the top five or 10. Develop a product that’s affordable, because at the moment, these therapeutics are unaffordable for lower income countries. And transfer this technology to 10 or 15 or 12 of the companies, to at least put a cancer therapy on the market and have the facilities running. And that’s the model that I would want to go full blast, to fundraise.

Q9: GHF: What is the timeline for development?

PT:

Seven years. So, over the next seven years, if this program (all 16 partners) can raise a billion dollars and of course that has to be diverse funding, it can’t just be grants, it has to be a combination of equity, debt, commercial returns and innovative funding models. I think for a billion dollars this program can develop a pipeline of life changing vaccines and therapeutics and narrow the pipeline and take five products into licensure. And I know some people are going to tell you “No, it’s going to cost you 20 billion”.

Listen, we in South Africa and Afrigen do very affordable development, if you have to do the same work here in the US and Europe, people cost you up to 10 times more (partly due to exchange rates). We know that we’ve done the comparisons. We know how cost effective we can do R&D in low-middle income countries, and I will continue to advocate for that. We can, for much less funding, take a product to work. Because remember, we’re not going to account for the grant funded R&D cost, and we’re not going to account for huge royalties coming back on a social goods product funded by grants. It’s a different business model.

Q10. GHF: On strategy that drove the transition from COVID-19 vaccination to diversify the portfolio, and the negotiations with the MPP.

PT:

So, we made an internal decision very early on. We’re biotech, we can’t operate on one product. We were acutely aware that we had to have backup compounds and come through with a pipeline. And we are acutely aware that we need to sweat the asset. We need to use this platform for sustainability. Any small company, any company, will tell you, this is how our minds work.

There were many discussions with the MPP around that, because where MPP came from was to honour the funders agreements: “you can’t go out of scope, this is a scope, and we don’t want you to divert your attention, because we all need to deliver on this”. And we had to juggle these balls in the air. And today it was the right thing to do. Because the absolute right thing to do is to just continue on in the background, start developing, testing the platform. And now today, this is the strategy for the mRNA program, because that is what is essential sustainability.

Moving forward I hope that they will be able to get late-stage products to codevelop or in-license that we can quickly take through to registration and the clinic. So, in these billion dollars must be not only greenfield development, it must be a portfolio - late stage, early stage, but prioritize products for which the market is uncertain but the need is great. Because nobody else is going to fund that, but where the burden of disease requires a product. That’s what we would try.

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