FDA Aims To Be ‘Nimble’ On COVID-19 Vaccine Changes For Variants

The agency is aiming to be “nimble” when it comes to evaluating COVID-19 vaccine tweaks to make them effective against the coronavirus mutations, says Marks, who heads the FDA’s Center for Biologics Evaluation and Research.

That means the agency will require some small studies, but not the large clinical trials that took companies months to recruit and complete the first time around.

“They’ll probably be studies involving a few hundreds of people, not thousands of people, again, to make sure that when we deploy something, it’s doing what it says it is and also so that we can understand some of these features of the immune response,” Marks said.

Acting FDA Commissioner Janet Woodcock told reporters on Feb. 4 that “we must prepare for all eventualities.” The agency will release guidance for industry in the coming weeks regarding the variants, she said.

How soon the guidance will be put to use is uncertain. “It will depend on how fast variants might emerge, to what extent the vaccines don’t provide protection and so forth,” Woodcock said during the press briefing. “So the situation is very fluid. But we think there are things short of doing full-fledged efficacy trials that we can use to shift or perhaps add components to existing vaccine.”

She said the agency would also most likely convene its advisory committee before authorizing any variant-related changes to existing vaccines. The same committee met late last year to evaluate and discuss the evidence concerning the Pfizer and Moderna vaccines before voting whether to recommend them for emergency use. The FDA usually follows the committee’s advice.

“I think it would be very wise, if we have the time, for us to have an advisory committee because that provides maximal public transparency,” she said. Vaccine hesitancy is already a problem, Woodcock noted. “The public is likely to be even more confused if, in fact, we develop variant strains, which we hope won’t happen.”

Three variants of concern have appeared in the United States: one first seen in Brazil, another identified in South Africa and the third one swept the United Kingdom. Mutations seen in these variants can help the virus infect healthy human cells more easily, and make it harder for the immune system to fight them off.

As of Wednesday, there have been 944 confirmed cases of coronavirus variants in the United States, according to the Centers for Disease Control and Prevention. All but 12 of these cases involved the variant first seen in the U.K..

It’s undoubtedly an underestimate because the U.S. has been slow to create a system to look for variants. The CDC has increased its sequencing of coronavirus testing about tenfold in the last three weeks, and expects to learn more about the variants’ true prevalence as time goes on, CDC Director Rochelle Walensky said at a White House briefing on Monday.

Meanwhile, the variant identified in the U.K. is likely to become the dominant strain of coronavirus in the United States by the end of March, Anthony Fauci, who leads the National Institute of Allergy and Infectious Diseases, said during the briefing.

Available data show the Pfizer and Moderna vaccines are still “quite effective” against the U.K. variant, Fauci said. He added that continuing to follow public health guidelines like social distancing and mask-wearing as well as vaccinating as many people as possible is “the best defense against the evolution of variance.”

Vaccines in the pipeline also appear to work against the variant strains, but they may not work as well.

For example, the vaccine made by Novavax has been shown to work against the variants identified in the U.K. and South African, but it’s not quite as effective against them. Meanwhile, South Africa paused its rollout of the AstraZeneca-Oxford vaccine because a small study suggested the shots only offered minimal protection against mild and moderate illness.

So far, it seems that we can still count on the Moderna and Pfizer vaccines for protection against the mutating virus, says Paul Offit, a member of the FDA advisory committee on vaccines. But preparation for the future would be prudent.

“We should get ready for this, get ready for the fact that these variants may become more resistant,” Offit said on a conference call organized by Georgetown University. “If you see people who are fully immunized with these vaccines — let’s say the mRNA vaccines — that nonetheless, when infected with the variant, are being hospitalized, that’s when the line gets crossed. And to date, that has not happened.”

Eventually, if COVID-19 becomes endemic, vaccines may get updated regularly like those for the flu.

But to adjust the influenza vaccine for each new flu season, the FDA doesn’t require clinical data. Instead, it primarily reviews information about the manufacturing process, said Norman Baylor, a former director of the FDA’s Office of Vaccines Research and Review. He was speaking at the press event organized by Georgetown University.

“But one of the differences is influenza vaccines are licensed. This vaccine [for COVID-19] is not licensed. And so … it has a minimum amount of data,” he said, referring to the fact that the COVID-19 vaccines are authorized for emergency use, but not yet approved. “So you want to see some data.” He suspects the agency will want to measure antibody levels in patients’ blood to determine how well updated vaccines protect against COVID-19 variants.

FDA approval updates aren’t limited to the flu vaccine, says, Jonathan Darrow, a lawyer with Harvard Medical School’s Program on Regulation, Therapeutics and Law.

“It’s actually very common for the FDA to approve supplements for changes to drugs and vaccines,” says Darrow. “Changes can include things like new or expanded populations, new active, new inactive ingredients, which they call excipients in manufacturing processes, or new diseases that the drug treats.”

There are at least three scenarios that could play out for updates to the COVID-19 vaccine, says Genevieve Kanter, a health economist at the University of Pennsylvania who has studied FDA drug and vaccine evaluations. The FDA could require an entirely new emergency use authorization; it could allow the manufacturers to submit an amendment to the existing emergency use authorization; or the original vaccines could have enough follow-up data to have achieved full FDA approval by the time an update is needed. In the last instance, updates would go through a standard supplemental approval process for changes in viral strains.

Based on what FDA officials have said, it seems as though an amended emergency use authorization is the option they’re leaning toward, she said.

Asked how long it might take the FDA to OK a tweaked vaccine or perhaps a third booster shot, Kanter said it’s tough to say. But there are clues in how the agency handled the H1N1 pandemic in 2009, when a vaccine change took a couple of months.

The FDA had approved vaccines for the seasonal flu in March of 2009, but the World Health Organization raised the alert about H1N1 in June. So that year’s vaccine needed an update.

“There was an advisory committee convened in July of that year, late July, to discuss clinical trials related to vaccines against the H1N1 strain and then by September, mid-September, four supplements had been approved against H1N1,” Kanter said. “So they can do it certainly in under two months.”

You can contact NPR pharmaceuticals correspondent Sydney Lupkin at slupkin@npr.org.

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