Europe’s challenge of a lifetime: Manufacturing enough coronavirus vaccines

The chances are that most coronavirus vaccines under development won’t work.

But even if one succeeds, there’s another hurdle: It needs to have a manufacturing and supply chain poised to produce and distribute billions of doses around the globe — a feat never attempted before.

This reality is causing drugmakers to scramble to get their hands on any available capacity. Pfizer and BioNTech, for example, are manufacturing the actual drug substance in both the U.S. and Germany, with later manufacturing set to be done at another U.S. site and in Belgium. AstraZeneca, which is developing and distributing the University of Oxford vaccine, has signed agreements with multiple manufacturing partners across the globe, including in Italy, the U.S. and the U.K. 

But they can’t get around the fact that vaccine manufacturing is an inherently risky venture, said Harris Makatsoris, professor of sustainable manufacturing systems at King’s College London.

To start with, “you have one group working really hard, on one particular vaccine candidate [and] one particular technology, and that group might be attached to a manufacturer in some shape or form,” he said. And this group needs to invest millions in manufacturing capacity specific to its vaccine, so “if it doesn’t work, then you have a big problem.”

The pandemic has forced an urgent response, with facilities getting converted and supply chains secured, all at enormous financial risk.

There’s also the issue that setting up vaccine manufacturing in parallel to vaccine development isn’t how it usually works, explained Charlie Weller, head of the Wellcome Trust’s vaccines program.

“You wouldn’t normally set up a manufacturing facility … until you know that your clinical data is safe and effective,” she said.

But the pandemic has forced an urgent response, with facilities getting converted and supply chains secured, all at enormous financial risk. In light of these costs, some of that risk is being mitigated by advance purchase agreements, with countries racing to agree to deals with the vaccine front-runners.

“It can take a decade to bring a new therapeutic or vaccine to market, and typically only one in 10 drugs that enter clinical trials make it to the market,” said Suzanne Farid, professor of bioprocess systems engineering at University College London.

What’s more, each vaccine developer works on the assumption that it may be the only one with a successful vaccine for some time, according to the Association of the British Pharmaceutical Industry’s Bryan Deane.

“They’re thinking large scale at the moment,” he said. “Because you’ve got no idea how quickly the second, third or fourth [vaccine] … would come through.”

But there is another problem — vaccines have global supply chains with a relatively small number of large companies that can deliver such vast quantities. One possible workaround, said Deane, is the creation of a “network of manufacturing sites around the world to help scale it up on behalf of everybody.”

Europe grapples with capacity

Given the dismal statistics on vaccine success, it’s no wonder experts are pointing to therapeutics and contact tracing as possible alternatives.

But countries around the world see a coronavirus jab as the great prize, which has led to vaccine nationalism as governments race to buy up future doses and ensure that they’re made as close to home as possible.

Whether Europe is able to manufacture enough vaccine for itself is the “billion-dollar question,” said King’s College London’s Makatsoris, admitting that international suppliers for the entire manufacturing process are still key for Europe.

Even DG SANTE’s outgoing director general, Anne Bucher, admitted in May that the vaccine production capacity in Europe wouldn’t be enough.

“The current production facilities will be insufficient to meet all the needs at the European level and also worldwide,” she told MEPs, adding that the Commission is in dialogue with the industry to see how it could help boost production capacity in Europe.

Many vaccines, many (different) challenges

Back at the lab, it’s the multitude of different vaccines that may pose obstacles in scaling up. Both the traditional and newer high-tech routes face challenges.

It’s about more than just producing billions of doses. It’s about ensuring that they get to the people who need them.

“If you’ve got a vaccine that, for example, works similarly to a flu vaccine, and you’ve already got large-scale capacity to be able to do that, then that’s a different scenario perhaps than if you’re working on new technology,” said the European Federation of Pharmaceutical Industries and Associations’ Andy Powrie-Smith.

But the old-school methods often make it harder to ratchet up production. For example, some vaccines need vast quantities of animal cells in their production.

“There’s a limited number of manufacturers that are in a position to grow animal cells at 2,000- or 5,000-liter scale,” said Udo Reichl, professor of bioprocess engineering at the Max Planck Institute for Dynamics of Complex Technical Systems. “Obviously, these plants are not sitting there and doing nothing. They’re usually busy with other things.”

Scale-up and speed problems are mostly solved when using high tech so-called platform technologies, experts say.

“You have the same production process, and with the same process, you can produce virtually any vaccine,” explained Zoltán Kis, research associate at Imperial College London’s Centre for Process Systems Engineering.

Some of the more promising vaccines use RNA, and these platforms have many advantages, including great speed.

So what’s the catch? This method has never actually been used to produce commercial vaccines.

There is another issue. These new technologies don’t solve the dilemma of how to fill the vials at the same speed. Kis explained that it’s “almost impossible” to fill the vials at the rate that the doses are produced, “even if you have a huge filling facility.”

But he and other scientists are coming up with workarounds. For example, rather than filling the liquid into tiny glass vials, it could be filled into bags, sort of like IV bags, but 200 doses at a time.

Another option could be multidose vials instead of single-use, which “can allow for more efficient production as they can be filled faster and stored more efficiently,” said Pam Siwik, Pfizer’s new product lead in its global manufacturing and supply team.

The big chill

It’s about more than just producing billions of doses. It’s about ensuring that they get to the people who need them, which requires proper storage conditions, said EFPIA’s Powrie-Smith.

Once the vials (or perhaps the IV bags) are filled, they need to be kept cold on their journey. Ordinarily, vaccines need to be held at a temperature of between 2 and 8 degrees Celsius.

Toby Peters, professor of cold economy at the University of Birmingham, calls this the “biggest logistical challenge we’ve ever faced.”

Broken cold chains are one of the main reasons for vaccine wastage. Estimates vary, but Peters cites figures of up to 50 percent of vaccines globally going to waste. “They mustn’t freeze, they mustn’t get too hot, otherwise they lose their potency,” he explained.

New technology RNA vaccines pose an even bigger problem, because there’s no certainty as to how stable they will be. In a worst-case scenario, they might need to be stored at minus 80 degrees Celsius at all times.

This setting is “not very convenient” for the many countries and places that “likely lack the basic infrastructure” to maintain this, Pfizer’s CEO Albert Bourla admitted at a briefing in May.

That’s why scientists like Peters are working hard to come up with solutions that don’t cost the earth — literally and figuratively.

“Cold chain is energy-intensive — it uses refrigerants, which have a big global warming impact,” he noted. “So can we do it in a way that harnesses other symbiotic processes or cooling systems?”

One possibility could be to tap into existing food supply chains, even using part of the cold storage facility at the back of a supermarket or an existing food chain logistics network.

But that doesn’t solve the next problem: When the vaccine arrives at the clinic or hospital, there may not be enough syringes and needles available to administer the jab. It’s something that Ian Lindsley, secretary of the European Biosafety Network, is worried about.

“Nobody in Europe seems to have got a grip of this issue,” he said.

The EBN has written to the European Commission and others to ask for clarity on the situation, but has not yet received a response.

What if it fails?

In the end, even if many of the vaccine candidates don’t succeed, the hundreds of millions pumped into manufacturing won’t be totally wasted, argues the Max Planck Institute’s Reichl.

“The companies are in a position to switch products if one approach isn’t successful,” he said.

One case in point is Pfizer, which admits its vaccine may not be the winner.

“Once any therapy or vaccine is approved, it will need to be rapidly scaled and deployed around the world” — Pam Siwik, Pfizer’s new product lead

“If unsuccessful, we’ll refocus as much of our effort as possible,” said Siwik. In fact, it may even mean supporting another pharmaceutical company.

“Once any therapy or vaccine is approved, it will need to be rapidly scaled and deployed around the world,” she said. “Pfizer is committed to using any excess manufacturing capacity and to potentially shifting production to support others in rapidly getting these life-saving breakthroughs into the hands of patients as quickly as possible.”

This article is part of POLITICO’s premium policy service: Pro HealthCare. From drug pricing, EMA, vaccines, pharma and more, our specialized journalists keep you on top of the topics driving the health care policy agenda. Email [email protected] for a complimentary trial.