Bottlenecks jeopardise efforts to produce millions of vaccine shots

IT IS perhaps the greatest manufacturing challenge since the Second World War. In the coming weeks and months the pharmaceutical firm Astrazeneca must turn the Oxford vaccine from a “little lab experiment” into an industrial weapon, replicated millions upon millions of times in the UK and across the world.

Nothing at this scale or speed has ever been attempted before; but the longer it takes, the longer the virus stays in charge.

Kate Bingham, chairman of the UK Vaccine Taskforce, laid out the challenge in an article for The Lancet last month. “The global manufacturing capacity for vaccines is vastly inadequate for the billions of doses that are needed, and the UK manufacturing capability to date has been equally scarce,” she wrote.

Astrazeneca is facing an uphill battle, having already fallen behind schedule. During the first wave, the company targeted 30 million doses ready for use in the UK by September, but now expects only four million by the end of the year.

In total the firm says it will have produced 20 million doses by the end of 2020, but these shots will not have been poured into vials, which takes time.

“These things are never easy,” said Matthew Duchars, chief executive of the UK Government-backed Vaccines Manufacturing and Innovation Centre, or VMIC, which has helped with production of the Oxford jab. “It’s not the case of flicking the switch and being able to manufacture straight out of the gate.”

Yet the early signs suggest that other countries that signed deals with AstraZeneca are far ahead of the UK, and may build up stocks more rapidly. The Bill Gates-funded Serum Institute of India, the world’s largest producer of vaccines, has already produced 40 million doses and plans to have 100 million ready by December. Those shots will go to Indians first, with further supplies handed next year to the Covax initiative to distribute the drug to poorer nations.

“The Indians are waiting for us to approve the vaccine so they can get going,” a Whitehall source said. “When we do, they’ll leave us behind very quickly in terms of numbers. They have a lot more capacity, it’s as simple as that.”

In recent months, a network of UK biomedical companies has been quietly trying to catch up. Oxford set up a “manufacturing task force” in April including the Portsmouth-based firm Pall Biotech, hired to draw up the entire end-to-end production process for the Oxford vaccine, a task that would usually take 18 months condensed into only eight weeks. The firm also continues to provide the crucial equipment including bioreactors, tubing and giant singleuse bags to brew the vaccine.

Dr Clive Glover, director of gene therapy strategy at Pall Biotech, said he believed the UK had already secured enough machinery and reactors in recent months to begin producing the vaccine at scale, but warned of further bottlenecks to come.

The “number one challenge”, he said, was the time it takes to complete the first stage; the production of raw vaccine. The process involves growing cells in large stainless-steel vessels while adding in the seed stock of the vaccine, and can take around three weeks. “Those mammalian cells grow slowly,” Dr Glover said. “I would argue that’s probably the biggest bottleneck that we have.”

After the first stage, the raw vaccine must be purified, put into giant bags, transported to be poured into vials, labelled and then distributed far and wide. By the end of the first quarter of the next year, Astrazeneca has predicted that it will have 300 million finished doses available across the world.

The UK has already ordered 100 million doses, and Astrazeneca has promised 40 million of those will be ready by the end of March.

But Dr Glover said he expected the UK’S full order of 100 million doses would not be in vials and ready to go until the end of next year at the earliest.

Another hurdle is the fact the Pall process is almost entirely single-use, with components needing to be thrown away and replaced after every batch to avoid contamination. Along with other firms across the world, Pall is now frantically producing bags, tubing and filters to meet the need, including at a factory north of Amsterdam.

“There’s no question that the demand for these kinds of consumables has ramped up significantly with all of these vaccine efforts. But we’ve been working very, very closely with the various parties to make sure that we’re able to deliver those at the right time. It hasn’t been a problem, so far,” Dr Glover said.

Along with Pall, the Oxford vaccine consortium includes the gene therapy firm Oxford Biomedica, which began manufacturing doses over the summer.

Under the terms of an 18-month agreement, Astrazeneca paid the firm £ 15 million upfront with a further £35 million to come for large-scale manufacture of multiple batches until the end of next year. “We are pulling out everything to get this over the line. We won’t be having much of a Christmas, put it that way,” a source at the firm said.

‘We are pulling out everything to get this over the line. We won’t be having much of a Christmas’