Tuesday, November 2, 2021

Can the UK deliver on the Covid vaccine rollout? | Stephen Buranyi

The UK has become the first country to approve one of the coronavirus vaccines that the entire world has been desperately waiting for. And on Tuesday it delivered the first dose, to 90-year-old Margaret Keenan in Coventry. We should be very pleased about this. But, as with every other stage of the pandemic, the final stretch brings a new set of unprecedented challenges. The world is watching as the UK becomes the first test case of our collective ability to manufacture, ship, and deliver an entirely new class of vaccines, on a scale and speed that no previous vaccination drive in history has ever approached.

The thing everyone knows about the Pfizer-BioNTech vaccine is that it needs to be extremely cold. The mRNA that makes up the vaccine payload is the same stuff your cells use to send short-lived genetic instructions. It’s a messenger that isn’t supposed to stick around, as temporally fragile as a Snap on Snapchat. The vaccine is happiest at -70C, and after thawing can be kept at between 4C and -8C – the temperature of a regular fridge – for just five days before it degrades. Most logistics providers aren’t set up to ship at -70C, and while university labs and large hospitals generally have some -70C freezers, GP surgeries and smaller centres do not. The temperature for shipping and storage has been identified as one of the biggest challenges in getting this vaccine out.

But here the UK is geographically lucky: our vaccine orders are being manufactured at a Pfizer factory in Puurs, Belgium, about two and a half hours away from Calais. All the orders so far have been shipped by lorry, and should be able to reach any location in the UK in under a day. The vaccine is placed in a specially designed box packed with dry ice, which should keep it at close to -70C for up to two weeks. The first few deliveries amount to 800,000 doses, which should give NHS providers a good test-run before ramping up to what Matt Hancock has promised will be “several million” vaccinations over the rest of the month, and then tens of millions in the new year. (The UK has ordered 40 million doses of the BioNtech-Pfizer vaccine – or 20 million two-shot treatments).

Quick Guide

How does the Pfizer/BioNTech Covid-19 vaccine work?


The Pfizer/BioNTech Covid jab is an mRNA vaccine. Essentially, mRNA is a molecule used by living cells to turn the gene sequences in DNA into the proteins that are the building blocks of all their fundamental structures. A segment of DNA gets copied (“transcribed”) into a piece of mRNA, which in turn gets “read” by the cell’s tools for synthesising proteins.

In the case of an mRNA vaccine, the virus’s mRNA is injected into the muscle, and our own cells then read it and synthesise the viral protein. The immune system reacts to these proteins – which can’t by themselves cause disease – just as if they’d been carried in on the whole virus. This generates a protective response that, studies suggest, lasts for some time.

The two first Covid-19 vaccines to announce phase 3 three trial results were mRNA-based. They were first off the blocks because, as soon as the genetic code of Sars-CoV-2 was known – it was published by the Chinese in January 2020 – companies that had been working on this technology were able to start producing the virus’s mRNA. Making conventional vaccines takes much longer.

Adam Finn, professor of paediatrics at the Bristol Children’s Vaccine Centre, University of Bristol

Unlike the disastrous rollouts of our testing and tracing services, which were largely outsourced to private providers, the NHS already has a lot of experience giving out jabs – mainly for the flu, where GPs administer 15 million in an average year. This system will be stretched, but we at least know there’s a minimum capacity.

At the moment jabs are being given at 50 NHS trusts across the country, which have the facilities and staff to handle the vaccine. There is a multi-tiered system of declining risk for choosing who gets the vaccine first, and the main difference with the Covid vaccine, compared with the flu jab, is that NHS providers will be working against the clock as soon as they thaw their stocks, running a sort of track and trace system to sort out the right people to get the vaccine in their catchment area, and then getting them in for the shot before the vaccine spoils. Bringing the vaccine to offsite locations has to be approved by the Medicines and Healthcare products Regulatory Agency (MHRA) – a plan to deliver to care-home residents was just approved a few days ago.

Countries that aren’t so small or close to the manufacturing source face even bigger issues. At Pfizer’s factory in Michigan, US, there are 20 flights a day ferrying vaccines across the nation and worldwide, where doctors will get the shots to administer to patients with even less time on the clock. The other approved mRNA vaccine, from the US biotech firm Moderna, is supposed to remain stable for up to 30 days in a regular fridge. Because both vaccines are made largely of the same components, it’s not clear why this is: Moderna has suggested in the media they have some propriety formula providing them an advantage. However, several scientists familiar with mRNA vaccines believe it would be a relatively simple tweak, requiring just a few weeks of testing, to make any mRNA vaccine store at a higher temperature.

If that’s true, it would not only be a huge relief not just for the countries who had already ordered vaccines, but also for the many poorer countries who have been cut out of the vaccine line twice: once by rich countries buying up the foreseeable supply, and then by their inability to set up hugely expensive cold transit and storage networks in just a few weeks.

But even if all the distribution and storage is sorted, the truly unpredictable element of the vaccine rollout will be shortages. Just after announcing their positive trial results on 9 November, Pfizer cut its planned 2020 vaccine production by half, from 100 million to 50 million doses, saying it had received some raw materials that weren’t of sufficiently high quality to use in production. It’s not clear what components these were. Part of the reason supplies of the vaccine will be so unpredictable is that pharmaceutical companies jealously guard their recipes and supplier relationships. It’s probable we’ll see similar problems occur again.

The process for making RNA is well established. The nearest university to you probably has a lab happily cranking it out as you read this. But most of the components for research grade RNA can’t be used for medical grade production. As with any item made to exacting specifications, when the standard of purity and cleanliness increases, the number of suppliers that can hit those marks dwindles.

Before Covid-19, RNA therapies were a relatively small and specialised field, so few suppliers are used to producing large volumes. One company, Acuitas, in Vancouver, Canada, developed the lipid-nanoparticle shell that holds the delicate RNA payload for three major RNA vaccine candidates, including Pfizer. Seven different candidates – again, including Pfizer – go to San Diego-based Trilink Biotechnologies for a vital RNA product called a 5’ cap. There are tens or hundreds of such relationships, dotted across the world, some known, some not. Any one could end up at a choke-point that snuffs out the production of tens of millions of doses.

I have heard it said that even after everything coronavirus has brought so far, shipping and distributing the vaccine is the real challenge. Regardless, that really undersells what a staggering step going from no vaccine to a vaccine is.

We can predict a lot about how the human body will behave, but you wouldn’t know it from the history of vaccine trials. Those things fail all the time, with little obvious explanation. Every one of the first wave of vaccine candidates could have failed and scientists would have shrugged and said “well, that happens”. But instead, we have several vaccines. We got incredibly lucky, and now our situation now seems much less beholden to chance. The challenges of delivering vaccines on this scale are hard, but they are firmly within the world of logistics, engineering, and politics. Unlike the uncertainty of the early pandemic, where no one knew how long it would go on, this a challenge we can measure. So it is finite, which is why it is finally the beginning of the end.

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