BioNTech tried to scuttle plans mooted by the World Health Organisation to have Africa manufacture Covid-19 vaccines, says an investigation by medical trade journal BMJ.

Pointing a finger at kENUP Foundation, a consultancy hired by BioNTech, BMJ said in its study released February 9, the firm protested WHO’s hub, saying it would infringe on patents and was unlikely to be successful.

The kENUP is supposed to promote global partnerships in research-based innovation for Europe with public and societal benefit.

BMJ said it had obtained documents containing the objections, and further details of kENUP promoting BioNTech’s plan to ship mRNA factories housed in sea containers from Europe to Africa.

According to the BioNTech plan, the sea containers would be staffed with BioNTech workers, and a proposed new regulatory pathway to approve the vaccines made in these factories, in a plot widely described as “paternalistic and unworkable” by some experts, as it seems to bypass local regulators.

Industrial consortiums

WHO’s technology transfer hub, launched June 2021 and based in South Africa, is using publicly available information to reverse engineer mRNA vaccines, like the Pfizer and Moderna ones, to teach companies and scientists across the continent how to use mRNA technology. The result would be that the companies develop a comparable vaccine, which, if successful in clinical trials and approved by regulators, they will manufacture industrially.

South African companies, Afrigen Biologics & Vaccines and the Biovac Institute, have joined a consortium to develop and manufacture the mRNA vaccine, with guidance from organisations including WHO, the Medicines Patent Pool, the South Africa Medical Research Council, and the Africa Centres for Disease Control (Africa CDC), as part of the wider Partners for African Vaccine Manufacturing project coordinated by Africa CDC, launched in April 2021.

In January, Afrigen Biologics announced it had successfully used the publicly available sequence of Moderna Inc’s mRNA Covid-19 vaccine to make its own version of the shot, which it hopes to take to clinical trials before the end of this year. It will be the first mRNA vaccine developed and produced at lab scale on the African continent.

Managing director of Afrigen Biologics Petro Terblanche said they would then experiment with other formulations that are cheaper to produce and do not need to be frozen in storage. He added Afrigen is in talks with two biotech companies to help scale up manufacturing.

BMJ says the kENUP Foundation wrote to South African government officials after a visit to the country on 11-14 August last year asking that the hub’s activities be stopped.

Reverse engineering

“The WHO Vaccine Technology Transfer Hub’s project of copying the manufacturing process of Moderna’s Covid-19 vaccine should be terminated immediately. This is to prevent damage to Afrigen, BioVac, and Moderna. Provided that the release from patent cover will be granted by Moderna only during the pandemic, the sustainability outlook for this project of the WHO Vaccine Technology Transfer Hub is not favourable,” BMJ quotes the dispatch.

The Medicines Patent Pool, which supports the WHO hub, responded in November to claims that this would infringe patents, saying, “The Medicines Patent Pool, which is responsible for the intellectual property and licensing elements of the hub, wishes to make it clear that this is not the case.”

South African law authorises scientists and manufacturers to carry out research and development regardless of patent protection, meaning that the hub’s reverse engineering of Moderna’s vaccine is legal, it added.

Moderna has also publicly promised not to enforce its Covid-related patents during the pandemic and said it was willing to license its intellectual property after that period.

The hub is in talks with Moderna to obtain such a licence.

Executive director of the Medicines Patents Pool Charles Gore, told BMJ that the rumours were “ridiculous,” saying such claims were “completely untrue.”

Public health advocate and lawyer Ellen Hoen told BMJ BioNTech should be accountable for kENUP’s actions.

“If you run a not-for-profit foundation and you go around trying to stop people from developing life-saving vaccines, then I don’t know what your agenda is but it smells really bad,” she said.

“If kENUP is on the BioNTech payroll, then BioNTech should be held accountable for this kind of behaviour.”

It was hoped that Pfizer-BioNTech or Moderna would share technology and know-how with the African hub, which could go on to teach local firms how to make the vaccines.

So far both companies have refused, although the hub is in discussions with Moderna over some form of collaboration — probably a voluntary licence, an authorisation given to companies to allow them to produce Moderna’s vaccine in exchange for a royalty.

Technology transfer

In a statement, a Moderna spokesperson said that trying to accelerate technology transfers could “put at risk” the delivery of its current production lines, with “negative efficiency, safety, and quality consequences.”

But BMJ says both Pfizer and BioNTech disagreed with this characterisation, arguing that sharing the technology would not lead to increased vaccine supplies in the short term and could take the raw ingredients needed away from established manufacturers.

In October 2021, five months after the hub was formally announced, both Moderna and BioNTech announced their own initiatives. Moderna announced that it would spend as much as $500 million to build its vaccine plant in Africa, aiming to make 500 million doses of mRNA vaccines each year.

It said that it planned to begin filling doses there in 2023 and hoped to make other mRNA products at the facility too.

That same month, BioNTech announced that it had signed memoranda with the governments of Rwanda and Senegal to build mRNA production facilities, with construction beginning in mid-2022.

Container factories

The kENUP’s Mission Report to South Africa, sent to the South African government last August, describes BioNTech’s initiative. It proposes exporting fully equipped mRNA production lines in a series of sea containers.

Made in Europe and staffed initially by BioNTech workers, these sea container factories would create the mRNA, the active ingredient of the vaccine, which would need to be put into vials by another company, a process known as “fill and finish”.

A second kENUP Foundation document, marked as “confidential” and sent to South African and European government officials in November, describes a framework to regulate such factories.

It suggested that in order to quickly begin producing mRNA vaccines in Africa, a new regulatory pathway should be agreed in which the sea container factories are licensed by the European Medicines Agency, claiming this would allow them to be fast-tracked for WHO pre-qualification, the global mechanism for ensuring a medicine’s safety, efficacy, and quality.

The document describes building up local regulatory capacity in the longer term.

But experts termed this concept flawed. Containers can be “useful innovations” for flexible manufacturing and distribution of vaccines, said Prashant Yadav, a fellow at the Centre for Global Development.

“However, they need to be approved by local regulatory bodies, and there should be a local quality responsible person from the country or site where such modular manufacturing is to be used,” he added.

Marie-Paule Kieny, who chairs the hub’s steering committee as chair of the Medicines Patent Pool and worked on vaccines at WHO, said that it was “pure nonsense” to believe that a European Medicines Agency licence that was intended to authorise vaccines used in Europe would apply to those made on a different continent under such different circumstances.

“Only somebody who doesn’t know how it works can say something like that,” she said.

Local regulators are needed to test vaccines before they are released to the market, something that European regulators will not carry out for African countries, said Kieny. She described kENUP’s proposed approach as “paternalistic” and advocated more locally owned schemes.

Margareth Sigonda-Ndomondo, who is leading on regulation for Partners for African Vaccine Manufacturing, said that her department had several interactions with kENUP about its white book and that it was “not well informed.”

She rejects the idea that the African regulatory system doesn’t have capacity and that another route for approval is needed.

“So, we have actually expressed our concern to say we do have existing systems on the continent,” she said.

“We have explained to them that all they need to do is to work within the existing initiatives, structures, and systems.”

The African Medicines Agency was ratified in 2021 and will harmonise regulation across the continent. South Africa has a laboratory able to carry out the necessary tests, which has been inspected by WHO, hopefully allowing its regulator to approve vaccines by the end of the year, she said. Once it does, it could act as a centre for excellence, supporting other regulators.

Sigonda-Ndomondo added that kENUP and BioNTech could not expect to bring in mRNA factories and expect African regulatory agencies to “give the go ahead without having to go through the scientific review process.”

However, she welcomed plans to build mRNA factories on the continent and said she would continue engaging with kENUP to find a solution that would allow African people access to these vaccines.

Others are waiting with interest for more granular details on the kENUP and BioNTech proposal. “The real proof of the pudding is going to be, ‘Will this vaccine, made in Rwanda and approved through this novel regulatory process, be accepted in Europe?’” said Patrick Tippoo, executive director of the African Vaccine Manufacturing Initiative and head of science and innovation at Biovac. “And if the answer to that is yes, then I would say, maybe it could be accepted in Africa as well.”

The push for Africa-made vaccines was launched owing to vast global inequities in Covid-19 vaccine distribution. So far 10.3 billion doses have been administered around the world, but only 392 million have been given out in African countries.

Afrigen and Biovac can manufacture as many as 500 million doses a year.

Martin Friede, coordinator of the Initiative for Vaccine Research at WHO, which is supporting the hub’s work, anticipates bottlenecks from shortages of reagents, glass vials, and trained staff. “The process of making the vaccine would have taken a year with the help of the companies, but without them it will take three,” said Mr Friede.