The U.S. government invested $ 1.6 billion in Novavax in 2020 – the most it spent on a vaccine maker at the time – in hopes it would offer the world another option for a safe vaccine and effective in helping to protect against Covid-19. But the company constantly encountered production problems. The methods it used to test the purity of the vaccine did not meet regulators’ standards and the company was unable to prove that it can produce an injection that still delivers, according to several people familiar with it. with the difficulties of Novavax. All spoke on condition of anonymity to discuss the company’s sensitive conversations.
Although Novavax recently testified to some of its analysis and testing problems in a quarterly filing with the Securities and Exchange Commission, the company’s issues are more of a concern than previously thought, according to two of the people with direct knowledge of the subject.
The Food and Drug Administration determines the purity levels with each manufacturer according to the June 2020 guidelines for coronavirus vaccines, but it is generally understood that each batch of vaccine must achieve at least 90%. The company has struggled to reach a level close to that, said one of those with first-hand knowledge of the situation. Another person familiar with the company’s manufacturing process said Novavax recently showed purity levels hovering around 70%. Low levels of purity increase the risk of contaminants or unnecessary substances in the final product, making the vaccine less effective or introducing the risk that patients will react to unknown ingredients.
COVAX, which recently lowered its 2021 target from 2 billion to 1.425 billion doses, has already estimated that it faces a supply gap of up to 1 billion doses in its efforts to immunize the developing world. If Novavax falters, it could double the deficit until 2022, leaving hundreds of millions of people without immunity to Covid-19 and prolonging the pandemic.
“COVAX continues to face adequate supply… in this context, Novavax’s challenges and manufacturing delays have been massively disruptive,” said Krishna Udayakumar, director of the Duke Global Health Innovation Center.
The global coalition is already behind on hundreds of millions of doses expected this month, having only shipped 371 million of its 700 million dose target for October. It now also risks missing its already lowered 2021 target.
Between Novavax and the obstacles of other manufacturers, “COVAX had to scramble to revise its sourcing strategy significantly in real time,” Udayakumar said. As a result, global health groups are emphasizing more donations to cover immediate needs, he added.
In a statement, Novavax senior vice president of investor relations and corporate affairs Silvia Taylor told POLITICO that the company’s analytical testing methods have been “validated” – but has not answered questions about whether the FDA had approved them. The company still plans to file an emergency use authorization by the end of the year, Taylor said.
“The vaccine development and regulatory submission processes are very complex and often take years to get to where we are now. We will fill all our committed doses both in the United States and around the world, ”Taylor said.
The White House and the Department of Health and Human Services did not respond to multiple requests for comment.
But three people familiar with the matter said they were not convinced the company had the resources to consistently reproduce a high-quality vaccine – a benchmark Novavax must reach before then. Those same people said Novavax could potentially fix its manufacturing issues and get a full license by the end of 2022.
Novavax – which has never produced a vaccine before – declined to respond specifically questions about the purity levels of her product and whether she had been successful in solving her long-standing manufacturing problems.
Unlike Pfizer and Moderna, the first manufacturers to launch vaccines using rapidly produced messenger RNA, Novavax uses the previously used but complicated approach of creating the key ingredient with bug cells. While the process of infecting cells to produce advanced proteins is familiar to scientists, it is difficult to scale.
The revelations of Novavax’s continuing manufacturing problems come at a time when only 36% of the world is vaccinated and as leaders in developing countries continue to pressure the United States to deliver more doses. In Africa alone, only 4.4 percent of the population is vaccinated.
This includes some of the most populous countries on the continent, such as Nigeria and Uganda, where around 1% of citizens are fully immunized.
Novavax is just the latest vaccine maker to experience baseline production issues after pledging to serve as a major contributor of vaccines to the developing world. In April, Johnson & Johnson halted work at a Baltimore facility operated by contract manufacturer Emergent BioSolutions after discovering that 15 million doses had been accidentally contaminated with ingredients from a separate Covid-19 vaccine.
J & J’s manufacturing process has been slow to recover and, to date, it has produced only a fraction of the 200 million shots originally pledged to COVAX by year-end, records show held by UNICEF.
“Excessive promises and under-deliveries are the name of the game for these manufacturers,” said Asia Russell, executive director of international advocacy group Health GAP. “And it is the infrastructure of the global response, which is terrifying. “
Unlike Johnson & Johnson, Novavax is new to the world of vaccines. He never successfully launched a vaccine and had struggled financially before the pandemic. After a series of drug development failures, it sold its manufacturing facilities in 2019 – a deal that also included the separation of 100 employees. In May of the same year, the Novavax share price fell to 36 cents per share.
Yet the company’s fortunes have changed as Covid-19 took hold. Amid an early pandemic rush to develop a range of vaccine candidates, the Trump administration granted Novavax $ 1.6 billion to help work on its Covid-19 shot – the biggest contract awarded to a manufacturer of Covid-19 vaccines at that time.
The contract represented a major vote of confidence in Novavax’s capabilities – and a gamble that appeared to pay off after late-stage trials showed the vaccine to be 90% effective against the virus.
But even then, senior Trump administration officials on Operation Warp Speed - a group tasked with accelerating vaccine development – repeatedly warned the company that it might face problems increasing the manufacture of the shot, said two people with direct knowledge of the discussions.
In particular, they were concerned that Novavax would struggle to ensure that the vaccine consistently meets stringent FDA quality standards once the vaccine goes into mass production – the exact problem that has stalled the company for months.
“They rushed the process,” said one of those familiar with the matter. “It’s hard to do. And they can’t do it.
Taylor, the spokesperson for Novavax, said in a statement that he had incorporated comments from regulators and had made “considerable progress in scaling up our commercial manufacturing processes.” The company is still on track to produce 150 million doses per month by the end of the year, she said, and has stored tens of millions of doses ahead of regulatory filings in the United States. And in the world.
Company executives in recent investor presentations have adopted an equally optimistic tone, downplaying manufacturing issues and predicting that it will soon be cleared to begin dispensing doses. At an investor-only event on September 29, chief trading officer John Trizzino said the company had “solved” its issues and was close to submitting a final regulatory request.
“We are really moving forward with testing our lots now,” added Gregory Glenn, president of research and development at Novavax, referring to his vaccine lots. “We think it will end soon. “
U.S. officials working with the company aren’t as confident, according to three people with knowledge of the matter. Novavax’s manufacturing issues are seen as much more difficult to resolve than the health and design issues that halted production of J & J’s vaccine at the Emergent plant earlier this year, the people said.
And even as the company begins to seek regulatory approval in other countries, there remains doubt in the United States that it has addressed fundamental flaws in the purity of the vaccine that people in the know have affected its ability to deliver doses in factories around the world.
Several batches of the vaccine have already been thrown away, and four people with knowledge of the matter say U.S. officials no longer expect the company to get FDA approval for the vaccine until next year at most. early.
“On some level, I think the effectiveness was never going to outweigh the risk associated with the impurity in it,” said one of the people familiar with the matter. “I’m not surprised that’s where we are at. “