Signs of internal turmoil at the Food and Drug Administration are raising concerns among former agency officials as widely anticipated deadlines on COVID-19 boosters and vaccines for children near.
A high-stakes debate about whether the booster shots are necessary recently led to upheaval at the FDA’s Office of Vaccines Research and Review, namely the sudden sidelining of that office’s two most experienced regulators.
The drama comes amid a critical month for U.S. vaccine policymaking. FDA documents on COVID-19 boosters for Moderna and Johnson & Johnson recipients are expected to become public ahead of meetings of the FDA’s independent advisers on vaccines next week.
Other FDA briefing documents on vaccines in children 5 to 11 years old are expected before the independent advisers meet again on Oct. 26. Many parents hope the advisers and then FDA will greenlight shots for kids just before Halloween.
Former FDA officials say the upcoming departure of top vaccine reviewers who were with the agency for decades could impair important analysis of the data.
The chaos in the vaccines office also underscores the fact that, nine months into the Biden administration, the FDA lacks a permanent leader. The White House has yet to nominate a commissioner. Acting Commissioner Janet Woodcock, a longtime career official, has temporarily led the FDA since January.
“There are strong reasons we don’t just go by a company’s press release or a paper in a journal. There were times when I was at FDA that we would have different conclusions than even the best medical journal,” said Jesse Goodman, a Georgetown University biotech policy expert and former FDA chief scientist. “When it comes to something that turns from the conclusion of a scientific paper to public health policy for the whole United States in the space of a few weeks, that’s when we need to be really careful to get it right.”
Goodman criticized Woodcock for signing off on an announcement by President Joe Biden recommending booster shots for every American by the week of Sept. 20, a recommendation that put pressure on the FDA and appears to have been premature.
“It’s important not just to have a permanent commissioner but also a permanent commissioner who understands the importance of these scientific agencies,” he said.
Dispute over boosters
Tensions rose when the FDA’s top vaccine reviewers, Office of Vaccines Research and Review Director Marion Gruber and Deputy Director Phil Krause, opposed the push to broadly offer third shots.
Their boss, Center for Biologics Evaluation and Research Director Peter Marks, supported the White House’s booster plan, but Gruber and Krause said immunity from two shots is durable for most people and that extra doses should be donated abroad. Gruber and Krause publicly announced their views in The Lancet and said they would retire later this year.
But last week, Marks, whose background is in cancer drugs, announced he would take over the vaccines office. The announcement came as a surprise, given that Gruber and Krause had previously announced they would stay on longer.
The upcoming departures of Gruber and Krause will result in four vacancies among the 31 leadership positions in the vaccines office listed on the CBER website.
“Peter Marks is not a vaccine expert,” said Norman Baylor, president of Biologics Consulting Group and former director of the FDA’s vaccines office. “He doesn’t have the years of regulating vaccines or understanding vaccinology like Phil and Marion.”
While directors of the vaccines office do not conduct hands-on reviews, they smooth out differences in interpretation among lower-ranking reviewers and resolve complex questions.
“If you’re a reviewer and you have a question, you have someone to huddle with who’s been in the trenches much longer on this subject matter. So it’s going to have an impact,” Baylor continued.
The news also rattled Goodman.
“While I had been disappointed that Dr. Gruber and Dr. Krause were going to leave the agency, I had been glad to see when that was announced that they were going to be there through this period where the booster and pediatric applications were being reviewed,” said Goodman, who once led CBER. “It was really unexpected when … the [CBER] director put himself in charge of that.”
‘Loss of expertise’
Goodman called it surprising that Marks assumed control of the office rather than promoting a vaccine expert.
“It represents a loss of expertise that could help them on those issues. It’s also a little unusual that you wouldn’t appoint someone from within that discipline or within that office,” he said. “There are other experienced people.”
The FDA said that during Marks’ nearly 10-year tenure at FDA, he has been “continuously involved” in supervising vaccine issues.
“More recently, Dr. Marks has been intimately involved in FDA’s work with COVID-19 vaccines, and has worked — and will continue to work — very closely with the subject matter experts in CBER’s Office of Vaccines Research and Review, whose work has been critical to the agency’s response to the COVID-19 pandemic,” said the statement. “Dr. Gruber will be retiring from FDA at the end of October, and Dr. Krause will be leaving in November. This period allows them both to have time to transition their work prior to their departures.”
The depth of analysis the FDA can conduct on the question of whether booster shots are necessary has been a sore spot for the departing regulators.
Krause bristled in a Sept. 17 public meeting with Pfizer, complaining that the drugmaker had not turned over much of its data for independent number crunching.
“One of the issues in this is that much of the data presented and being discussed today is not peer-reviewed and has not been reviewed by FDA,” he said, before highlighting a study that he interpreted to show much higher efficacy of two shots in people over 65 years old than Pfizer had claimed.
Meanwhile, in order to determine whether immunity had waned, the FDA requested a study from Pfizer that compared clinical trial participants who had received a placebo and “crossed over” to receive a vaccine more recently with people who received the vaccine months earlier.
But while Pfizer presented the findings, the datasets were not submitted to the FDA and the FDA did not independently verify them, FDA briefing documents state.
Goodman said Biden’s announcement that the U.S. booster program would begin during the week of Sept. 20, which occurred in advance of FDA decision-making, undermined the scientific review.
“There were studies that were important in the [FDA’s vaccine advisers’] review and the FDA’s review that had not been provided to FDA in time for them to fully analyze them,” he said.
“Those data are being used without taking the days or weeks it would require for FDA to perform their own analysis,” Goodman added.
“That’s just horrible. I’m surprised people haven’t made more noise about that,” said Peter Lurie, president of the Center for Science in the Public Interest and former associate commissioner for public health strategy and analysis at the FDA, referring to the lack of FDA analysis on the Pfizer datasets. “The thing that sets FDA apart from all other drug regulatory agencies is the claim that it independently analyzes the data that comes from drug companies.”
The FDA did not respond to a request for comment.
Workload weakens morale
Krause’s criticism of Pfizer’s analysis occurred during a meeting of the FDA’s independent advisers, the Vaccines and Related Biological Products Advisory Committee, and may have influenced its members’ decision to reject booster shots for most Americans.
The vote helped shape the FDA’s decision to pare down Pfizer’s request for approval of its booster shot for Americans age 16 or older to an authorization for just the Americans most vulnerable to severe disease or infection.
Without Gruber and Krause on hand to ask critical questions in full view of the FDA’s independent advisers and the public, those gaps in analysis may not cause the same stir when it comes to booster shots for Moderna and Johnson & Johnson or shots for children under age 12 later this month.
Meanwhile, agency morale is strained under the intense workload, former FDA officials say.
A recruiter for the pharmaceutical industry, who did not want to be named to protect her job, said it is easier than ever to hire FDA employees who might have stayed in public service if not for the pandemic.
While disagreement among scientists on high-profile decisions affecting the public health of millions of Americans is expected, the level of dissent spilling into view may be unprecedented.
“This is unusual,” said Baylor. “There’s always internal debate and disagreement. But then you reach consensus. At least in the 20 years I worked there, that’s the way we worked.”
“There are many internal meetings and discussions and then you come out in lockstep with what the consensus is,” Baylor continued. “This seems like the gulf is so wide, there may not be consensus.”