Africa’s struggle to secure a steady supply of Covid-19 shots has made it clear how this dependence on only a few manufacturers is shooting the continent in the foot — when what we really need are shots in the arm. The World Health Organisation (WHO) projects that only five of the 54 countries in Africa will hit the organisation’s target of 40% of their populations being fully vaccinated by the end of the year.
But Africa’s reliance on pharmaceutical companies in other parts of the world can be turned around.
The WHO’s plan to establish mRNA vaccine technology transfer hubs — one of them in South Africa — aims to do exactly that. The hubs in low- and middle-income countries will work with local companies, scientists and academics to figure out the methods of making specific vaccines, the equipment and skills needed to produce them and train local manufacturers to make the vaccines.
The centres will, at least initially, focus on mRNA jabs, such as the Covid vaccines manufactured by Pfizer and Moderna.
mRNA vaccines use pieces of man-made genetic material to instruct the body to produce proteins that can fight a particular virus. The type of genetic material such vaccines use is called messenger ribonucleic acid, or mRNA. mRNA delivers instructions to cells to create the required viral protein, which in turn prompts the immune system to fight the virus whenever it encounters it.
In South Africa, a company called Afrigen Biologics and Vaccines has been appointed as part of a group of collaborators to develop the technology for making an mRNA vaccine based on Moderna’s recipe. But they have to crack the method themselves because Moderna has refused to be part of the hub and transfer technology.
We break down what this means, why it’s crucial for helping developing countries become more self-sufficient and why Big Pharma is not keen.
Tech transfer in a nutshell
Vaccine technology has changed a lot from the “fairly simple, straightforward process” of producing inactivated viral vaccines, Barry Schoub, professor emeritus of virology at the University of the Witwatersrand and chair of the ministerial advisory committee on Covid vaccines, told Bhekisisa in May. Inactivated viral vaccines, such as those used against measles, polio or whooping cough, contain a virus whose genetic material has been destroyed so that it can no longer infect cells and cause disease, yet still trigger an immune response. This approach has been the mainstay of vaccine production for more than 60 years.
Today, there are new ways of making vaccines, using mRNA, recombinant nanoparticles (tiny genetically engineered particles that carry immune-prompting proteins) and viral vectors (a harmless virus that carries the instruction for making specific immune-prompting proteins). Some of these technologies have been put to use to make Covid-19 vaccines. But these methods need fairly advanced starter materials, equipment and technical know-how. And this is where tech transfer comes in.
To be able to make one of these modern vaccines quickly and efficiently, it requires exact information about everything that’s needed for producing a safe and effective vaccine — from the recipe and ingredients to the tools, training on how to use them, safety protocols and checklists for testing the quality of the final product.
“There’s a considerable difference between knowledge transfer and tech transfer,” says Petro Terblanche, managing director of Afrigen. Even with independent scientists sharing their know-how on mRNA tech, safety issues and engineering requirements, piecing together the process is time-consuming.
With proper tech transfer, vaccine production has the potential to become a plug-and-play affair. Local manufacturers will be able to set up facilities to produce jabs at scale without having to trudge through the treacle of development trial and error themselves. And this is what the WHO is trying to do with their hub-and-spoke model. A central partner, in this case Afrigen, develops the technology and then gives manufacturing partners their “build-a-vaccine” info pack so that they can set up production facilities locally.
Had Moderna been prepared to share its technology, Afrigen wouldn’t have had to first try to figure out the recipe and equipment required — the WHO hub would have been able to start with training African companies straight away and helping them to set up their manufacturing plants.
A is for access
Knowing exactly what ingredients, tools and facilities you need, how to set everything up and how to go about making a vaccine and doing quality checks, means commercial-ready production can be in the order of months rather than years. In fact, both BioNTech (which manufactures the Pfizer vaccine) and Lonza (which manufactures Moderna’s vaccine) were able to produce vaccine doses commercially within six months after tech transfer from their pharmaceutical developer partners started.
But there’s big money to be made in medicine, and Big Pharma doesn’t seem to be keen to play ball except with their own production partners, which they get to choose and manage.
Both Pfizer and Moderna — a relatively new player in pharmaceutical development — recently announced staggering earnings driven by their vaccine development. This has led to public outcry and increasing calls for tech share, especially as considerable amounts of public money were used in Germany and the United States to fund BioNTech and Moderna’s respective development of Covid vaccines.
Access to technical know-how needn’t be free, says Terblanche. “We would have been happy to produce Moderna’s vaccine under a voluntary licence, agreed under terms that are fair to low- and middle-income countries. We weren’t asking to get it for free, just to be treated as equal partners.”
Under a voluntary licence a patent-holder (such as a pharmaceutical company) gives another company permission to use its patents and other trade secrets to make a generic version of a specific product — at a fee.
World Trade Organisation member countries are currently considering a proposal, drafted by South Africa and India, for waiving the intellectual property (IP) rights — the legal mechanism that protects an inventor’s trade secrets and patents — of producing Covid technologies such as protective equipment, treatments and vaccines. “But IP is just one barrier,” says Kate Stegeman, advocacy coordinator in South Africa for Doctors Without Borders. “Sharing the know-how is still an issue.”
In October last year, Moderna said they wouldn’t enforce their Covid-19-related patents against other companies that want to make a vaccine like theirs during the pandemic, and made their patents publicly available. But just because they said they won’t sue doesn’t mean it’s straightforward for someone to copy their method.
“By nature, patents are dense, complex documents, and the patent for a vaccine even more so because of the many different ingredients and steps needed to make it,” says Terblanche. “The developer always has some tacit information built up through experience, which doesn’t get included. It’s not malicious, it’s just how patents are written.”
Afrigen has so far gathered “all the relevant information we could get in the public domain”, from the patents to the research articles, conference proceedings and expert sessions, including sessions hosted by Moderna.
“Our scientists interpret it all and add their own expertise and innovation, to help us make a vaccine that will be as safe and effective as Moderna’s, but hopefully won’t need such extreme refrigeration,” Terblanche says. “We want to make a vaccine that will work for Africa.”
Andy Gray, a senior lecturer in pharmacology at the University of KwaZulu-Natal, summarises the challenges Afrigen faces well: “The patent might disclose the bare bones of an invention sufficient to describe it and meet the standards of patentability – but it always holds back on some know-how that would make it difficult for anyone else to exploit that patent and that knowledge. Technology transfer is really about the know-how and the fine details that are not disclosed in a patent.”
B is for building a vaccine
Making a vaccine follows a fairly standard process — whether it’s for the conventional type using an inactivated virus or one based on new technology such as what is used to make Covid-19 vaccines
- First you have to make the drug substance, which is the active ingredient that will cause the immune response. For a conventional vaccine, such as the polio jab, it’s the inactivated form of the actual disease-causing virus, harvested from cells grown in a lab (cell cultures). In the case of an mRNA vaccine , it’s a strand of mRNA. For a viral-vector vaccine (such as the Johnson & Johnson jab), it’s a harmless carrier virus (typically a flu-type virus) that delivers the instructions that prompt the body to launch an immune response.
- Then you have to mix it with other ingredients to make up a solution that can be delivered into the body, either by swallowing or injection. This process is called formulation.
- The next step is to fill small vials with the vaccine, do all the needed safety and quality checks and then distribute the vaccine.
mRNA COVID vaccines seem to be the best choice for rapidly upscaled production. A fairly small amount of starter materials yields a lot of final product, and the parts of the mRNA strand can also be changed quite easily to adapt the vaccine when a new variant arises. But making up the solution into a format that will get it to the right place in the body intact is challenging. This is mostly because the mRNA strand has to be wrapped in a lipid nanoparticle — a small fat-based particle that can fuse with cell membranes and so let the mRNA enter the cell.
According to Terblanche, getting the lipid nanoparticle right is one of their biggest challenges, because they have to figure out how to do it from research principles — rather than following an existing, proven method as would have been possible had Moderna transferred their technology.
Another hurdle in producing a vaccine without tech transfer is quality control. “A vaccine has to be safe, effective and affordable,” Terblanche says. Deciphering how to get to that point without help wastes a lot of time, which could be avoided if an inventor shares their safety protocols and quality assurance methods as part of a tech transfer deal.
But Morena Makhoana, chief executive of Biovac, a Cape Town-based pharmaceutical company that will handle vaccine manufacturing of Moderna as part of the local WHO vaccine tech transfer hub, cautions safety checks take long — even when the inventor has shared their protocols. Before even approaching a medicines regulator such as the South African Health Products Regulatory Authority to approve a vaccine for local use, a manufacturer has to do a series of production simulations with water, trial runs with the actual product, and eventually complete three full, glitch-free manufacturing cycles with three different batches of product to show that they can make the vaccine efficiently and that the product is stable. “Only then do you go to the regulator,” Makhoana says.
C is for capacity and continuity
Being able to produce vaccines locally — even when under licence from a pharmaceutical developer — can set countries up to help themselves to fight disease outbreaks. “The WHO’s vaccine tech transfer hubs align with a strategic plan for Africa to be able to supply 60% of its vaccine requirement itself by 2040,” says Terblanche.
Stavros Nicolaou, South Africa’s Aspen Pharmacare’s head of strategic trade, agrees. Aspen has a contract with J&J to “fill and finish” their COvid jab, which means J&J sends them the drug substance or active ingredient produced in Europe and they then mix it, put the jabs in vials, label and distribute it. But this means that Aspen doesn’t own the final product and can’t decide who to sell it to. Instead, they have to hand over the finished jabs to J&J.
Earlier this year, there was a controversy about J&J sending shots “filled and finished” by Aspen to Europe, while South Africa didn’t have any J&J vaccines. The company was criticised and then decided to send the vaccines from Europe back to South Africa for distribution in South Africa and other African countries.
Nicolaou says they are in talks with J&J about getting a licence to produce the vaccine at their Gqeberha plant from start to finish, rather than just doing the “fill and finish” of the jabs. “If we can produce the product here in full, it will mean that we can supply the region rapidly and directly,” he says.
Vaccine tech transfer — whether it happens directly from pharmaceutical companies or through hubs such as those of the WHO — goes beyond Covid-19, because it puts the expertise and facilities in place to fight other epidemics too. Ultimately, it prepares countries such as South Africa for the next outbreak that will hit. Because it will.
Nicolaou concludes: “Tech transfer today will allow us to be known for African elephants, not white elephants.”