The ABCs of DIY vaccines: Why tech transfer is a big thing
Africa could cut its reliance on vaccine manufacturers outside the continent before the next health crisis hits, if a new World Health Organisation initiative takes off. But for that to happen, pharmaceutical firms will need to share more than just their patents
The struggle to secure a steady supply of Covid shots has made it strikingly clear how this dependence on only a few manufacturers is shooting the continent in the foot, when what it really needs are shots in the arm: the World Health Organisation (WHO) projects that only five of Africa’s 54 countries will hit the target of fully vaccinating 40% of their populations by the end of the year.
But Africa’s reliance on external pharmaceutical companies to make jabs can be turned around.
The WHO’s plan to establish mRNA vaccine technology transfer hubs – one of them in SA – 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 for making specific jabs, what equipment and skills are needed to produce them, and then train other 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 – called messenger ribonucleic acid (mRNA) – to instruct your body to produce proteins that can fight a particular virus. mRNA delivers instructions to your cells to create the required viral protein, which in turn prompts your immune system to fight the virus whenever it encounters it.
In SA, a company called Afrigen Biologics & Vaccines has been appointed as part of a group of collaborators to develop the tech for making an mRNA vaccine based on Moderna’s recipe. The problem is that it essentially has to crack the method, because Moderna has refused to be part of the hub and initiate a “tech transfer”.
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 Wits University 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 it can still trigger an immune response. This approach has been the mainstay of vaccine production for more than 60 years.
Today, though, there are new ways of making vaccines, such as using mRNA, recombinant nanoparticles (tiny genetically engineered particles that carry immune-prompting proteins) or 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 vaccines. But these methods all 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, you essentially need a flat pack – the equivalent of what you need to put together a piece of furniture yourself. So you require the exact information about everything that’s needed to produce a safe and effective vaccine: from the recipe and ingredients, to the tools that would be required, the training 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 Afrigen MD Petro Terblanche. But even with independent scientists sharing their know-how, 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. And this is what the WHO is trying to do with its hub-and-spoke model: a central partner like Afrigen develops the technology and then gives manufacturing partners a “build-a-vaccine” info pack so they can set up production facilities locally.
Had Moderna been prepared to share its technology, Afrigen would not have had to first figure out the recipe and equipment; the WHO hub would have been able to start training African companies straight away, and helping them 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 market-ready production can be achieved in a matter of months. 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 of tech transfer from their pharmaceutical developer partners.
But there’s big money to be made in medicine, and Big Pharma doesn’t seem to be keen to play ball – except with its own production partners, which it gets to choose and manage.
Both Pfizer and Moderna recently announced staggering earnings, driven by their vaccine development. This has led to a public outcry – and increasing calls for tech share – especially as considerable amounts of public money were used in Germany and the US to fund BioNTech’s and Moderna’s Covid vaccine development.
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 SA and India, to waive the intellectual property (IP) rights around producing Covid technologies such as protective equipment, treatments and vaccines. “But IP is just one barrier,” says Kate Stegeman, advocacy co-ordinator in SA for Doctors Without Borders. “Sharing the know-how is still an issue.”
Last October, Moderna said it won’t enforce its Covid-related patents against other companies during the pandemic, and made its patents publicly available. But just because the company said it wouldn’t sue doesn’t mean it’s straightforward for someone to copy its method.
“By nature, patents are dense, complex documents, and the patent for a vaccine [is] even more so because of the many different ingredients and steps needed to make it,” explains 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:
- First, you have to make the drug substance, which is the active ingredient that causes the immune response. For a conventional vaccine such as the polio jab, it’s the inactivated form of the 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 J&J 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 mix the drug substance 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, perform 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 parts of the mRNA strand can also be changed quite easily to adapt the vaccine when a new variant arises. But it’s challenging to make up the solution into a format that will get it to the right place in the body. 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 the biggest challenges, because Afrigen has to figure out how to do it from research principles – rather than by following an existing, proven method, as would have been possible had Moderna transferred its 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 that could be avoided if an inventor shares its safety protocols and quality assurance methods.
But Morena Makhoana, CEO 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 that safety checks take a long time – even when the inventor has shared its protocols.
Before even approaching a medicines regulator such as the SA 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 complete three glitch-free manufacturing cycles with three different batches of product to show the vaccine can be made 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 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,” explains Terblanche.
Stavros Nicolaou, Aspen Pharmacare’s head of strategic trade, agrees. Aspen has a contract with J&J to “fill and finish” its Covid jab, which means J&J sends Aspen the drug substance or active ingredient produced in Europe and the company formulates (mixes) it, puts the jabs in vials, and labels and distributes them. But Aspen doesn’t own the final product, and it can’t decide who to sell it to. Instead, it has to hand over the finished jabs to J&J.
Earlier this year, there was huge controversy around J&J sending shots “filled and finished” by Aspen to Europe while SA didn’t have any J&J vaccines. After being heavily criticised, the company then decided to send the vaccines back from Europe for distribution in SA and other African countries.
But Nicolaou says Aspen is in talks with J&J about getting a licence to produce the vaccine at its Gqeberha plant, rather than just doing the “fill and finish”. “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 via hubs such as the WHO’s — goes beyond Covid, because it puts the expertise and facilities in place to fight other epidemics too. Ultimately, it prepares countries such as SA for the next outbreak that will hit. Because it will.
As Nicolaou says: “Tech transfer today will allow us to be known for African elephants, not white elephants.”
Sulcas writes about global health and food systems, and worked previously at the Global Fund to Fight Aids, TB and malaria, and the WHO. She is former editor of the Global Fund Observer. Pretorius is a freelance science writer and editor, focusing on health and science education
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