Under fire, FDA to issue stricter guidance for Covid-19 vaccine EUA this week — report
The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.
The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.
“This step should help reassure Americans that FDA’s career scientists with responsibility for regulating vaccines have their back and are making decisions based on sound science,” former FDA chief scientist Luciana Borio told Endpoints News in an email, adding they “ensure that only vaccines with adequate safety and meaningful effectiveness data are granted an EUA.”
Most notable among the new regulations is a provision that calls for vaccine manufacturers seeking an EUA follow subjects for a median of at least 60 days following the second dose of the vaccine. It also asks them to accrue at least 5 cases of severe Covid-19 in the placebo group, a measure that will be significantly harder to hit than the metrics in the current trial protocols.
CBER chief Peter Marks had pointed to some of these measures in prior appearances, but they were not part of public guidelines.
The Post report says the guidelines could come as soon as this week.
Although the original FDA guidance called for long-term followup of trial participants, as is routine in vaccine studies, it did not set a bar for how long volunteers had to be monitored before developers filed for an EUA. And while it called for the vaccine to be 50% effective, the agency left open to manufacturers whether they would define that as effective in preventing infection or preventing disease.
The newly released Phase III protocol for Pfizer, whose CEO Albert Bourla has been the most vocal of any pharmaceutical executive in promising Covid-19 vaccine data before November, revealed that the company was using a relatively low bar for efficacy compared to Moderna, counting any of a long list of symptoms as “disease.” Moderna and AstraZeneca also did not require instances of severe disease.
News of the new guidelines came on the same day that well-known scientists – albeit not vaccinologists – raised concerns in The New York Times and The Post opinion sections that the criteria Moderna and Pfizer picked were not stringent enough. Others argue bar for efficacy was also in line with WHO guidance, allows for faster answers and is not uncommon in vaccine development.
The new guidelines, though, almost certainly increase the amount of time needed to determine safety and efficacy.
“It’s hard to imagine how an EUA could possibly occur before December,” Paul Offit, a prominent vaccinologist and member of the FDA’s vaccines AdComm, told The Post.
Eric Topol, who called in The Times for harder efficacy standards and was a critic of the FDA’s conduct on the EUA for convalescent plasma, praised the move.
And this FDA announcement today is most welcome, moving in the right direction. #NoRushJobhttps://t.co/ndRojjEgrn
w/ @PeterHotez @califf001 @DrPaulOffit
by @lauriemcginley2 and @Carolynyjohnson 9/ pic.twitter.com/GhlgDCoXLF
— Eric Topol (@EricTopol) September 22, 2020
Still, it’s not clear who will have final decision making power on these vaccines. Earlier this week in a memo panned by one former FDA associate commissioner as a “power grab,” HHS chief Alex Azar stripped the FDA’s ability to make rules without his signature. An HHS spokesperson said concerns were overblown and called the memo an example of “good governance” and had nothing to do with vaccines.
FDA commissioner Stephen Hahn, vested with the authority as final decision maker on the nation’s drugs, reports directly to HHS Secretary Alex Azar. The FDA commissioner doesn’t have to follow agency advice and it while it would be an extraordinary breach of precedent, experts say the HHS secretary could issue an approval himself.
Rachel Sachs, a law professor at Washington University at St Louis, said federal statutes make clear that the final decision rests with the HHS secretary, noting that in one high-profile instance during the Obama Administration, the secretary overruled FDA commissioner Margaret Hamburg on access rules for “Plan B.” But she called that case the “exception that proves the rule” of the agency’s independence and said she was skeptical Azar would overrule Hahn.
“It would be very difficult for the secretary of HHS to authorize the vaccines over objections of FDA, procedurally as well as politically,” she told Endpoints News, noting Marks’ promise to resign if the agency okayed an unproven vaccine.
A former FDA official, though, said there’s yet a chance these guidelines don’t become policy. It hasn’t been released and officials could yet stop them.
“Wanting to see at least some severe cases, and wanting 2 months safety data sound like reasonable precautions,” former FDA chief scientist Jesse Goodman told Endpoints in an email. “I am concerned that now that this is leaked someone may try to stop it.”