The coordinator of the AccessIBSA project, which campaigns for access to medicines in India, Brazil, and South Africa, and a vaccine expert from the Médecins Sans Frontières (MSF or Doctors Without Borders) Access Campaign published a report today identifying over 100 companies in Africa, Asia, and Latin America with the potential to produce mRNA vaccines for the Covid-19 response. Human Rights Watch wrote to the US and German governments urging them to act on this research. Human Rights Watch’s European media director, Andrew Stroehlein, sat down (virtually) with the report’s co-author, Achal Prabhala*, to discuss the findings and methodology. Prabhala also described what should now happen to expand vaccine production globally, so we can fight the virus more effectively.
Stroehlein: Since the mRNA vaccines were developed to help fight Covid-19, their manufacturers have been claiming that the process is complicated and very few companies can manufacture them. Your report has provided a list of over 100 companies in Africa, Asia, and Latin America with the potential to manufacture mRNA vaccines. Can you tell us a bit more?
Prabhala: The report that Alain Alsalhani** and I co-authored builds on recent research findings from MSF and Imperial College, and to an extent on earlier research published by Public Citizen. Our report really goes to the heart of the argument that pharmaceutical companies producing mRNA vaccines have put out. We’re saying a few different things. Of course, vaccines are complex and hard to make. But of all the vaccine technologies that are in use today, the oldest are in fact the hardest to make, and the newest – mRNA vaccines – the easiest. Despite what they’ve been saying about this new generation of vaccines, the fact is, they are actually easier to make than any of the old-style vaccines and that opens up a whole wide range of possibilities in terms of who can make them.
Stroehlein: That will surprise some people. People often think of newer technology as being more complicated than older technology.
Prabhala: That’s simply not the case with mRNA vaccines. If we look at older vaccine technologies, we see a very time-consuming, complicated production process, one that depends on growing cells and biological organisms: there is no way to simplify it. It’s all extremely tricky to monitor. Relatively few manufacturers can do it. And until last year, all vaccines produced anywhere in the world involved the growing of cells or some kind of biological organism. The oldest technology in use in the pandemic is the inactivated virus vaccine – where the virus is “killed” – and it’s been around since the 19th century. The vaccines from Sinovac and Sinopharm in China, and Bharat Biotech in India, are examples of this technology. They are, hands-down, the hardest vaccines to make, since their manufacture involves handling live pathogens and can therefore only be done in highly secure facilities of which there are very few in the world. It is to these companies’ credit that despite the production challenges, they have managed to make their vaccines in such large quantities in the pandemic.
Stroehlein: So, with the production of these new mRNA vaccines, you don’t need any of those biological steps?
Prabhala: Exactly. You can think of mRNA vaccines as a hack. They can be synthesized biochemically in a test tube but will appear to the human body as if they were made by biology. Unlike with older generations of vaccines, you don’t have to worry about growing cells, or their variability, or a host of added precautions. That’s all avoided, because with mRNA vaccines you have a stable process that utilizes routine biochemistry, and results in precise, predictable outcomes.
Stroehlein: That’s the real breakthrough with mRNA vaccines, then? That production is actually easier compared with old-style vaccines?
Prabhala: Indeed. We’ve been given to understand that the singular thing about mRNA vaccines is that they work better than other vaccines. That’s true, though other vaccines work well enough too. But the real breakthrough with mRNA – and this has been buried, to good effect – is that they are far, far, easier to make.
Stroehlein: So, when producing mRNA vaccines, it’s more like anyone can make them following a recipe?
Prabhala: Well, of course, it’s not something you and I can do in our kitchens, but it is something that many drug manufacturers can do as long as they’re willing to invest in the resources they will need, from training to facilities and equipment. It might be helpful to think of the drug industry like a three-tiered pyramid. At the top, you have a few vaccine manufacturers, who can produce old-style vaccine technology. In the middle, you have a few more manufacturers who can produce biologics, a class of drugs very similar to vaccines. At the bottom are a large number of companies who make chemistry-based pharmaceuticals. And any company in this bottom layer who also makes injectable drugs, or “sterile injectables” to be precise – as many of them do – can theoretically make an mRNA vaccine. As, obviously, can any company in the top two layers as well, since all vaccines and biologics are sterile injectables, but not vice versa.
Stroehlein: What is a “sterile injectable”?
Prabhala: It’s basically what it sounds like: a drug that is produced in a sterile environment, with a sterile process, from start to finish, and then poured into a vial and delivered to humans by an injection. As long as you have that kind of facility, and you have experience running a facility like that, you can theoretically make mRNA vaccines. It’s not like every company out there that makes aspirin can do it, of course, but there are a substantial number of them. Many existing manufacturers around the world could make them. At least over a hundred by our count, in fact.
Stroehlein: So, these are the criteria you looked for in compiling this list?
Prabhala: Yes. We found many existing manufacturers that fall into this category, that have facilities for producing chemistry-based pharmaceuticals as sterile injectables. If they were allowed to – if they could have the recipe and the permission, as it were – they could be producing Covid vaccines in three to six months.
Stroehlein: And that would obviously help with the problem of the billions of people in the world who haven’t even been able to get a single dose of the vaccine yet. But what about safety? How can we be sure these are reliable producers?
Prabhala: We added some filters to our list, which is why we say “at least” over a hundred companies. In order to get on this list, a manufacturer not only had to be producing sterile injectables, but also had to have exported their sterile injectables successfully to the European Union or the United States, or been evaluated by the World Health Organization (WHO). The EU, the US, and the WHO have high standards for what they called “good manufacturing practices” or GMP. What this means is that before a drug can be sold in the EU or the US, or through the WHO, the factory that made the drug has to be certified for meeting the gold-standard quality requirements that the EU, the US and the WHO demand.
Stroehlein: So, the EU, for example, can’t say that these companies are incapable of making safe injectable drugs, because these companies are already producing safe drugs that are being injected into the arms of people in the EU every day?
Stroehlein: What other things did you consider when creating this list?
Prabhala: We went deeper into evaluating what this capacity to make mRNA vaccines looks like in practice with a small, representative sample of these companies across a few countries. Even assuming things like intellectual property monopolies are suspended or licensed, and that the vaccine technology is shared with them, not every company might want to make mRNA vaccines immediately, and one of the main reasons why they may not want to is because of the capital investment required to do so. But given the staggering need for mRNA technology both now and in the future, for example with booster shots for Covid but also as a basis for vaccines and drugs for other diseases, there’s a good business proposition here. The investments are also manageable, given the size of many of these companies: a total outlay of between US$127 million and US$270 million, according to MSF & Imperial College, to produce 100 million vaccine doses, depending on which technology is used.
Stroehlein: That seems like a lot.
Prabhala: It does, but not when we consider that a single vaccine dose is currently selling at more than US$1.27, or even US$2.70. Plus, at this stage of the pandemic, there are all kinds of financing options available, both in terms of the capital market itself but also international organizations and governments that are willing to invest in or loan money to vaccine production.
Stroehlein: OK, but what about space in the facilities themselves?
Prabhala: This was another surprise. To make 100 million doses a year of an mRNA vaccine, MSF & Imperial College estimate that a company needs between 200 and 240 square meters of “grade C” space, which is the technical term for facilities that have the right air filtration and other sterile conditions. That’s something like 2,500 square feet.
Stroehlein: About 230 square meters, hardly any space at all. That’s like a three-bedroom apartment in some cities.
Prabhala: Amazing, isn’t it? Most of these companies either already have that kind of space, or could set it up easily.
Stroehlein: OK, let’s talk a bit more about the companies themselves. Could you give us an example of one?
Prabhala: We found capable, certified-quality companies across the world, including in Egypt, Morocco, Tunisia, Senegal, South Africa, India, China, South Korea, Vietnam, Malaysia, Bangladesh, Chile, Argentina, and Brazil.
Let’s start with Sothema in Morocco. The company was founded 45 years ago and earns annual revenue of about US$177 million. Sothema has traditionally made what we call small molecules, or chemistry-based products, and is a great example for the potential to make mRNA vaccines that exists in companies who have not made vaccines or biology-based products before. They have the space, they have the capacity and the ambition to make mRNA vaccines, and they have multiple quality certifications of their facilities, including from the EU. They are currently running fill-and-finish work for vaccines from Sinopharm, and are eager to expand into the mRNA space.
Then there’s Biocon in India. It's over 40 years old, has around 12,000 employees and annual revenue in excess of US$900 million. Biocon has been exporting drugs to the US and European market for years, and they make biologics, a complex category of drugs, very similar to vaccines. Biocon is a prime example of the kind of company with experience in biology-based products that could be contributing to mRNA vaccine production, and wants to be, but is not. Their facilities meet the quality standards of the EU and US, they have experience in making complex pharmaceuticals, and they have the financial muscle to get in the game.
Stroehlein: What would you say to the hardcore skeptics who say there is still no proof that companies in developing countries can produce mRNA vaccines?
Prabhala: In the past, Biocon, like other similar companies based outside the West, faced outright skepticism about their ability to produce the complex biological drugs I mentioned, which are, probably more difficult to make than mRNA vaccines. The company had to overcome waves of doubt that they could indeed produce these drugs at an international quality level, just like they and a hundred-plus other companies around the world are now facing the same doubt over their ability to make mRNA vaccines.
Stroehlein: So, they’ve been here before, and they’ve proven themselves.
Prabhala: Yes. You know, as we’ve been talking to pharmaceutical manufacturers on this exercise, we could really feel their frustration. For them, it's a bit like being an Olympic runner, but not even being allowed to start the race because somebody's tied your feet to the starting blocks. The fact that there are so many of these companies out there with the willingness and ability to help us fight this global pandemic, but are being denied the opportunity to do so, does strike me as a ridiculous mistake.
Stroehlein: If more companies like this were able to be involved, the global model we’d be looking at then would be a kind of distributed production model, involving a large number of facilities around the world. But why would this be a better solution than, say, having the US government simply pay Pfizer and Moderna large amounts of money to make a larger quantity of their vaccine, as they are doing now, in a very limited way?
Prabhala: If these companies could make enough doses for everyone, they’d be doing it already. The current global shortage of vaccines suggests that they simply cannot. Plus, getting companies on different continents to make these vaccines just makes sense, for our immediate problem now, and for the future. A centralized source, or a small concentration of producers, is putting all our global health eggs in one basket. It’s not smart, and it’s precisely why we’ve failed to vaccinate the world so far. All the charity in the world put together will be less useful than simply giving countries – or continents – the ability to take care of themselves. With all these experienced, qualified manufacturers out there, we have a tremendous opportunity to boost vaccine production globally, and we need governments, especially the US and Germany, to help make that happen.
Stroehlein: What about training and capacity building needs? How can the US and German government help?
Prabhala: First, there’s a lot that these companies with the ability to make mRNA vaccines can do for themselves, without the kind of extensive help, financially and technically, we may think they need. Second, there is absolutely a role for the US and German governments, especially with the actual transfer of technology. Companies like BioNTech, Pfizer, and Moderna may say they have physical limits on how many people they can be on the phone with, or visit, at the same time. Fair point. It would help the process if governments were to work with these companies and set up and fund a human bridge that would make the transfer of technology faster, easier, and ultimately more successful.
Stroehlein: OK, so, there’s all these potential new producers out there. Talk us through exactly what these 100+ companies would need to start making an mRNA vaccine. How is this connected to the TRIPs waiver, the proposal at the World Trade Organization to temporarily waive some intellectual property rules on vaccines and other health products?
Prabhala: Let’s start with what the TRIPs waiver is, and what it requires to become a reality. There is huge momentum worldwide for it, and I hope it happens. The TRIPs waiver is international; those who wish to utilize the waiver, for instance, most countries in which the companies we’ve identified are located, would first need to enact national legislation to make the TRIPs waiver work locally. The benefit of acting under a TRIPs waiver, rather than going at it alone, which is theoretically legally permissible and possible, is twofold: it would allow countries to act in concert with each other, and it would offer some protection to any country doing so against retaliation for offending commercial interests in the US and the EU.
Then, let’s go to what the TRIPs waiver can do. It can provide companies in countries which have enacted the waiver locally, a freedom to operate. It can remove the legal constraints a local company may have to create a diagnostic test, or an antiviral pill, or even a vaccine. In addition, it can provide companies the ability to make the diagnostic test or that antiviral pill, because tests are not complicated to replicate and antiviral pills are what we call “small molecules” or relatively simple pharmaceuticals, where the only thing usually blocking their production is the intellectual property around them, in the form of patents. I should add here that creating easy and fast compulsory licensing norms – a legal measure by which the patent monopoly is overridden – is an option that countries could use to achieve something close to this effect, as the new Brazilian law has done.
The TRIPs waiver has ingenious provisions to transfer the vaccine recipe to interested manufacturers, whether the originators of the vaccines want that or not. The TRIPs waiver will need to be complemented with the actual vaccine technology to be transferred in order for more vaccines to be made immediately.
Stroehlein: What needs to happen for manufacturers around the world to make vaccines immediately?
Prabhala: Companies like BioNTech, Pfizer, and Moderna should be licensing other companies outside Europe and the US to make their vaccines right now, but they’re doing very little; and for all the talk from the US and German governments about vaccinating the world, they’ve not put enough pressure on these companies to do what the world needs them to. As a start, these companies could license their vaccines to the WHO’s mRNA production hub in South Africa; given that we now have a potentially more dangerous variant, Omicron, detected in the region. But they need not stop there. Many of the 120 manufacturers we’ve identified here could be licensed to make these mRNA vaccines, and in fact, doing so would be the fastest and surest way to ensuring the world makes billions more vaccines as quickly as possible.
Stroehlein: If we’re trying to ramp up the production of vaccines globally as quickly as possible, that makes a lot of sense. But what if those companies simply don’t want to cooperate?
Prabhala: Our call answers this fundamental problem. The TRIPS waiver and technology transfers are complementary measures. The TRIPs waiver could give manufacturers in some countries access to the regulatory dossier, or the recipe. The way it would do this is to give regulators – the equivalents of the US Food and Drug Administration or the European Medicines Agency – the permission to share the dossier they receive from Moderna or Pfizer/BioNTech for approval. Normally, regulators keep these dossiers confidential; under a TRIPs waiver, in the way it was originally proposed, willing regulators would be able to share this recipe with other capable manufacturers that they choose to share this with, without retaliation. And while this is a lot, in order to make vaccines, we will still need collaboration from the originator company, or access to what we call their supply chain, that is, the materials needed to begin, and the possibility of having expert human assistance from them. That’s why we’re calling for Moderna and Pfizer/BioNTech to join the WHO hub and engage in bilateral technology transfers with as many of the companies we have identified in our list as possible.
Stroehlein: Could you explain the link between the vaccine recipe and vaccine approvals?
Prabhala: This is complicated, but I’ll try and explain it as simply as possible. If we had a full, collaborative, technology transfer in the way I just described, that would make production by other capable manufacturers faster, and it would allow those manufacturers to rely more or less entirely on the troves of manufacturing and clinical data generated by the originator company for its own regulatory submission. What this means is that a company in, say, South Africa, or Brazil, or India, would not need its own regulatory approval if it were operating under a license from Moderna or Pfizer/BioNTech and that would save a lot of time. If, however, the company is developing a “copy” of the vaccine independently, let’s say by using the helpful but limited knowledge in the regulatory dossier that was shared with the manufacturer, it would have to generate a new dossier, most important, around clinical proof of safety and efficacy for their “copy.” In the future, it is possible that a follow-on mRNA vaccine could be approved like a generic medicine, without the need for extensive clinical testing, but we are not there yet, and in this moment, we need immediate solutions. At the same time, we can and must work on better long-term outcomes, for example, through the TRIPS waiver and regulatory reform, to create a more conducive environment for mRNA vaccine manufacturing, by allowing regulation around mRNA technology to become more independent of originator companies, but all of that can only happen in the future, and not immediately.
Stroehlein: Are you hoping that these combined actions – the TRIPs waiver proposal, the call for more licensing of vaccine technology, and the identification of these 120 companies who can make an mRNA vaccine – will push originator companies into working more collaboratively?
Prabhala: Absolutely. The reason Pfizer is sharing its Covid pill through the Medicines Patent Pool to almost a hundred countries and letting any manufacturer in these countries make it is because it knows that if it didn’t, these countries could take action on their own to make that happen anyway. There is a legal solution to generating more production of Pfizer’s Covid pill. The reason Pfizer is not sharing its Covid vaccine in a similar fashion is because vaccines come with additional barriers, and require full technology transfers, which, at the moment at least, there’s no way to get without Pfizer’s collaboration.
Here’s the thing. At the moment, given all the complex global rules, the decks are stacked in favor of mRNA vaccine manufacturers like Moderna, Pfizer, and BioNTech. They know that. The TRIPs waiver will open up the production of diagnostic tests and drugs immediately, and tip the scales for vaccine production in the medium to long term. Government pressure from the US and Germany to make companies like Moderna, Pfizer, and BioNTech collaborate will tip the scales for vaccine production immediately. The demand for Covid vaccines is not going to go away. We’re seeing third-shot boosters rolling out in a number of countries while billions of people in the world await their first shot. We have a new variant, Omicron, which has already resulted in an increased demand for vaccines worldwide. I know the technical and legal issues can get pretty complicated here, but the bottom line is: there’s a horrific global shortage of vaccine doses. We need to boost vaccine production worldwide, mRNA vaccines are ideally placed to fill this gap quickly, and there are many, many, companies around the world that could make those vaccines, if we allow them to.
*Achal Prabhala coordinates the AccessIBSA project, which campaigns for access to medicines and vaccines in India, Brazil, and South Africa. He founded the project in 2016 from a Shuttleworth Foundation Fellowship he was awarded in the same year. He grew up in India and trained in economics and public policy management in the United States. He began working on access to medicines in South Africa in 2003, during the HIV/AIDS crisis that engulfed the country at the time. He has worked on a number of landmark cases concerning pharmaceutical industry monopolies, including Novartis’ ultimately unsuccessful challenge of Indian patent law in 2007. Between 2011 and 2019, he served on the Expert Advisory Group of the Medicines Patent Pool. Through the pandemic, he has worked on a range of initiatives to increase vaccine access, including through public media and an interdisciplinary research project on the policy frameworks that restrict access to biologic drugs and vaccines.
**Alain Alsalhani is an industrial pharmacist by training and holds master’s degrees in pharmaceutical regulation and in public health. Before joining MSF, he worked in the pharmaceutical industry, including with Sanofi Pasteur. With MSF, Alsalhani worked as a project pharmacist in places like Haiti and Turkey. He then spent two years in India sourcing medical supplies for MSF local and global operations. In 2015, he joined the MSF Access Campaign as vaccines and special projects pharmacist. His areas of interest and work include vaccines technology transfer and manufacturing in low- and middle-income countries, regulatory systems strengthening and quality of generic medicines. Since the beginning of the current pandemic, he has been following the development, manufacturing, and supply of COVID-19 vaccines. He is the civil society representative in COVAX’s manufacturing working group. He grew up in Damascus, Syria, before travelling to France for his pharmacy studies.