- Biovac will become the first company in Africa to produce Pfizer/BioNTech’s COVID jab — but they won’t produce the vaccine from scratch. The SA manufacturer will import the drug substance (the active ingredient that makes the vaccine work) from Europe and “fill and finish” the shot in South Africa.
- Pfizer/BioNTech is an mRNA vaccine. The companies will transfer mRNA technology such as equipment installation to Biovac and the company will start with the production process in early 2022. The jabs will go to African Union member states.
- In June it was also announced that Biovac would be one of the partners in the World Health Organisation’s mRNA vaccine technology transfer hub. The hub will train manufacturers from low- and middle-income countries in how to make mRNA vaccines — and help them obtain the licenses to do so.
- But technology transfer is complex and can take months. We break down why.
What would happen if COVID vaccine manufacturers such as Pfizer/BioNTech and Moderna gave up their intellectual property rights tomorrow and agreed to share the recipes of their shots with South Africa?
The short answer is that the country still wouldn’t be able to make the jabs, because it wouldn’t know how to formulate the recipes. The longer explanation is that it will take many months for South Africa to master the technology and skills required to add the ingredients of the recipes together in the right way.
As it stands, only two companies in the country are capable of making vaccines. But neither biopharmaceutical firm Biovac nor Aspen Pharmacare can make jabs from scratch. For South Africa to learn how to use their vaccine recipes, Pfizer/BioNTech and Moderna would need to do something called “technology transfer”.
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Merely giving South Africa the instructions to make a shot would be a little like giving a recipe for a molecular-cuisine dish to someone who has only ever made toast – and then expecting them to cook it to a Michelin three-star standard.
Where intellectual property is the theory of how to make something, technology transfer is the practice of that theory. It requires a company to share its expertise, experience, tips and insights on making a product.
An intellectual property waiver isn’t enough
Within the context of a pandemic with a severe shortage of jabs, an attempt to compel manufacturers to share their COVID vaccine recipes is currently underway — but getting them to transfer technology might be infinitely more difficult.
In October, South Africa and India tabled a proposal at the World Trade Organisation asking its 164 member states to agree to temporarily suspend all intellectual property rules in their countries for COVID-related products and technologies, including vaccines.
If this proposal is accepted, it will force pharmaceutical companies in member countries to share their patents. The idea is to address the inequitable distribution of jabs, where rich countries have bought up most of the shots, and poorer countries are at the back of the queue.
But while such a waiver will remove drug companies’ exclusive rights to produce their COVID jabs (and other COVID treatments), it won’t necessarily compel them to share their know-how — that will be determined by the laws of individual countries and the steps such governments are prepared to take.
And even then, transferring technology could take months – or years.
COVID mRNA vaccines use technology that has never before been brought to market for any product, let alone produced in South Africa. This technology uses pieces of man-made genetic material to instruct your body to produce proteins that can fight a particular virus. In the case of SARS-CoV-2, the virus that causes COVID, mRNA jabs use a genetic code of the spike protein on SARS-CoV-2 to get your body to make antibodies that can fight this novel coronavirus.
At an African Union (AU) conference in April, Moderna CEO Stéphane Bancel said the technology transfer process for the manufacturing of mRNA jabs – if it happens – will take a minimum of six to nine months. In addition to this, a factory would need the mRNA active ingredient or drug substance – the key ingredient that makes the vaccine work – which is extremely complex to make.
mRNA jabs have proved to be some of the most effective jabs against COVID, and South Africa is using Pfizer/BioNTech’s shot, which is also effective against both the Beta (currently dominant in the country) and Delta (rapidly spreading in South Africa and likely to become dominant) variants, as part of its national vaccine roll-out.
Kickstarting vaccine production in Africa
In late June, the World Health Organisation (WHO), along with Biovac, local biotech outfit Afrigen Biologics and Vaccines, a network of universities, and the Africa Centres for Disease Control and Prevention (Africa CDC), announced that it will establish a facility that will help to bridge the “know-how” gap: a COVID mRNA vaccine technology transfer hub for Africa, in South Africa.
The WHO says the hub will kickstart vaccine production on the continent by acting as a training facility where mRNA technology “is established at industrial scale and clinical development performed”. The hub will train manufacturers from low- and middle-income countries to use mRNA vaccine recipes, and it will help them obtain the licences to do so.
For the hub, which will be set up over two years, Biovac will act as a developer, Afrigen as a manufacturer and the universities as academic support, providing mRNA know-how. The Africa CDC will provide technical and regional support.
Biovac and Afrigen will therefore be the first recipients of “cutting-edge mRNA vaccine know-how” under this programme, according to South Africa’s ministry of higher education, science and innovation.
Biovac isn’t new to technology transfer. The company has secured high-profile technology transfers from Pfizer for its Prevnar13 pneumonia vaccine and from Sanofi Pasteur for its Hexaxim jab, which protects against five childhood diseases, including polio, whooping cough and tetanus.
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But the licensing agreements with both companies are for the “fill-and-finish” of the vaccines, not for manufacturing that starts with production of the active substance, says South Africa’s Biovac CEO Dr Morena Makhoana. For Prevnar13, for example, which protects against 13 different types of pneumococcal bacteria, Biovac receives 13 different bags of drug substance from Pfizer and then adds it together, puts it in vials and packages it.
Higher education, science and technology minister Blade Nzimande says it’s essential that the technology used at the WHO hub is “either free of intellectual property constraints in low- and middle-income countries, or that such rights are made available to the technology hub and the future recipients of the technology through non-exclusive licences to produce, export and distribute” those vaccines in such countries.
As Kate Stegeman, Doctors Without Borders’ access campaign advocacy co-ordinator in South Africa, explains it: “What needs to happen next is Moderna and Pfizer/BioNTech must immediately share their mRNA technology with the hub so that many more mRNA vaccines can be produced independently by manufacturers in South Africa and more broadly on the African continent, as soon as possible.”
The hub will also use something called patent pooling to negotiate access to licences for mRNA technology for trainee manufacturers. To do this, it will work with an organisation known as the Medicines Patent Pool (MPP), which negotiates with drug companies “to pool intellectual property to encourage generic manufacture and the development of new formulations”.
The MPP has, for instance, helped some poorer countries to get licences to produce antiretroviral drugs (ARVs), for HIV treatment by signing agreements with ARV patent holders.
What goes into making mRNA vaccines?
According to Bancel, there’s an array of set-up requirements for the production of Moderna’s jab: getting the specific, tailor-made machines; securing financial investment ($20m-$30m); creating the right safety protocols; ensuring approval of production sites by different regulatory agencies; and getting the appropriately skilled people hired and trained.
“It would take a minimum of six to nine months, even if you have a clean suite already,” he told the AU conference, referring to facilities that already have pharmaceutical-grade cleanliness, pressure, temperature-control, humidity and sterility standards.
In addition, Bancel said, Moderna has its own skills bottleneck, given that mRNA technology is so new. “I can’t [even] hire people now who know mRNA,” he said. “The challenge now is that teams are running flat out, and we’ve not even finished doing all the tech transfer to deliver [current orders] for this year.”
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The making of an mRNA vaccine is a very different process to that of “traditional” vaccines – especially the way in which the drug substance is made. A drug substance or active ingredient is the ingredient that makes the jab work.
For Pfizer-BioNTech’s mRNA vaccine, there is an 18-step manufacturing process, from modifying bacteria and inserting “plasmid” rings of DNA (small, round DNA molecules found in bacteria and other cells) with coronavirus genes into them, to growing the cell, fermenting the mixtures, harvesting the DNA and transcribing the DNA into messenger RNA that will, after several more steps, end up in a vial ready to use. Some of these steps are so highly specialised that, even in the US, they are performed sequentially in different facilities.
“The more mid-term framework for me,” Bancel said, while expressing willingness to engage in technology transfer to enable Africa to manufacture Moderna’s mRNA products, “is what do we do to stand Africa on its feet in terms of technology.”
Why mRNA vaccines might be the best way forward for Africa
Bancel believes vaccines using messenger RNA technology might be easier for South Africa and Africa to produce, partly because of the “modular” nature of the production process – different parts of the process can (and do) happen in different locations, and the equipment required is smaller and less expensive than that used for the older, more conventional types of vaccines, such as viral vectors (the technology used for the Johnson & Johnson vaccine).
This is because a very small volume of raw material used as the active ingredient for mRNA vaccines can eventually yield huge quantities of vaccine. In the case of the Pfizer-BioNTech COVID vaccine, one single vial of the DNA with which the production process begins can ultimately generate 50-million doses.
This doesn’t mean it would be “easy” to recreate the vaccine from scratch – but it does mean that, in the medium and longer term, mRNA technology may be well suited to countries looking to quickly and relatively inexpensively set up “fill-and-finish” facilities to produce mRNA vaccines.
“The modular concept is a good concept and probably going to be the way of the future,” says South Africa’s Biovac’s Makhoana. “But I don’t think it has been tested as widely as you would like. And what is ‘modular’? You still need to have the same infrastructure, all the bells and whistles. How is it going to move the needle? If we ever have an opportunity to talk to Moderna, that is where the part of the know-how and the technology transfer needs to be.”