The article was a shock. The medical journal Lancet had just published a review by an international roster of scientists — including Marks’s top two vaccine officials — that argued forcefully against administering boosters to the general public, at least for now.
The public nature of the dissent and the timing were stunning. The FDA is scheduled to meet Friday with its vaccine advisory committee to discuss whether to approve a Pfizer-BioNTech booster, the start of what the Biden administration hopes will be a rollout of extra shots for all three vaccines used in the United States. But now, the two officials, who typically play major roles in running such meetings, had publicly rejected the need for boosters even before the session — a strikingly unusual development.
For the Biden administration, the episode signals the bumpy road ahead for the drive to implement vaccine boosters. And for the FDA, the controversy over whether — and when — to approve the shots is part of a tumultuous season with few parallels.
Enraged parents are demanding the agency approve vaccines for their children. Clashes — both within the FDA and with other parts of the administration — are spilling into view, confusing a public already unnerved by a capricious virus.
The picture is about to get even more complicated. Over the next several weeks, the agency — which oversees products including sunscreen, cosmetics and cancer drugs, but these days is known for ruling on coronavirus vaccines and treatments — faces an onslaught of decisions. These judgment calls could help determine whether the coronavirus pandemic will be brought under control anytime soon or whether it will continue to menace the economy and spawn battles from one end of the country to the other.
“There have been key moments in the agency’s history — and this moment, with all the decisions facing FDA, is definitely in the top five,” said Jeff Nesbit, who led the FDA’s communications during the George H.W. Bush administration.
The moment is occurring as staffers find themselves overwhelmed and exhausted by a crushing workload; the vaccine operation alone faces three years’ worth of work that must be done in the next six months, according to one estimate. And it comes as some Biden administration officials are expressing dissatisfaction with the FDA’s pace and as the FDA regularly tangles with the Centers for Disease Control and Prevention over key vaccine issues.
“I think we have got a real problem here,” said Eric Topol, professor of molecular medicine at Scripps Research. “The last thing we need right now is all this infighting. We need a unified front. The virus is the enemy.”
The Friday advisory committee meeting is sure to prove contentious: Some of the panel members are outspoken critics of administering boosters to the public at this time. While many FDA watchers had assumed the agency would approve the Pfizer-BioNTech booster in coming days, that could be harder to do if the advisory committee is opposed or split on the issue. The FDA is not required to follow the recommendations of its outside advisers but often does.
An agency staff review released Wednesday in advance of the committee meeting took a noncommittal tone on whether a booster was necessary for the general population. It noted that some studies have suggested the vaccine’s efficacy declines over time against symptomatic infections, but some have not.
The Lancet article went much further. The review said there was little data to justify a booster for most people now, considering the shots’ robust protection against severe disease and the potential risks associated with unnecessary additional injections. The authors wrote that even if the boosters were helpful at some point, it would be more beneficial to offer shots to countries where people have not had access — essentially the World Health Organization position.
The FDA officials — Marion Gruber, the longtime director of the Office of Vaccines Research and Review, and Philip Krause, her deputy — indicated that their views represented their own opinions. The two had recently announced they would be leaving the agency this year. Part of the reason was their unhappiness about the administration’s push for booster shots, according to a former FDA official who retains close ties to the agency. The official spoke on the condition of anonymity to discuss private conversations.
The FDA on Wednesday released the agenda for Friday’s meeting showing that Gruber will make opening remarks. But FDA observers predicted Marks would take a significant role in the session following the tense developments of recent days.
Gruber and Krause did not respond to emails requesting comment.
A few hours after the Lancet article was published on Monday, Marks took issue with its conclusion, arguing it did not reflect the latest data from Israel, which has been the source of extensive information on the Pfizer-BioNTech vaccine.
“I’m fully confident that when people come to the advisory committee meeting … and they witness the Israelis presenting their data and they witness other data being presented that there will be a good rationale for why boosters might be necessary,” Marks said Monday at a conference by the Regulatory Affairs Professionals Society. And he said his job was to protect people in the United States.
The FDA declined to make Marks available for an interview but answered some questions in writing.
The new Israeli information, which will be presented at the committee meeting, is likely to bolster previous data showing that protection from the vaccine, including from severe illnesses and hospitalizations, wanes while a booster strongly increases immunity. Some scientists have warned that the Israeli data has limitations.
If the FDA approves the Pfizer-BioNTech booster soon for all adults vaccinated six to eight months earlier — the approach outlined last month by senior administration health advisers — the agency could come into conflict with the CDC and its advisers. The FDA determines when shots are safe and effective. The CDC’s Advisory Committee on Immunization Practices provides recommendations on who should get the shots. That panel has talked about recommending boosters initially only for nursing home residents, health-care workers and people 65 and older.
The FDA said in a statement that its collaboration with the CDC has “a positive impact on our nation’s public health” and that the agencies will continue to share responsibilities on vaccines.
Pfizer boosters are just one item on the FDA’s urgent “to do” list for vaccines. Others include clearing vaccines for children younger than 12 and deciding when to authorize Moderna and Johnson & Johnson boosters. The workload is taking its toll.
“The staff have the same issues as everyone else — they have had to put off seeing elderly relatives and are worried about their kids being exposed to the virus,” the former FDA official said. “They also are tasked with the horrible problems you see in the news every day. They are having a lot of burnout.”
Even as the agency struggles, President Biden has not nominated a commissioner and instead has relied on a longtime career official, Janet Woodcock, to serve as acting commissioner. While Woodcock is seen as a steady hand with deep experience, the lack of a permanent commissioner has injected further uncertainty as a November deadline approaches for Biden to nominate a full-time leader.
“You want to have someone who can speak to the American people and champion and defend the FDA’s decisions with authority,” said Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine. “If you have an acting commissioner there, you always have an asterisk.”
This was supposed to be an easier year for the FDA than 2020, when the Trump White House pushed relentlessly for the agency’s endorsement of hydroxychloroquine, an untested coronavirus treatment, and convalescent plasma, a therapy whose benefits were misrepresented in a high-profile news conference last year. Political appointees at the Department of Health and Human Services pushed to strip the FDA of key authority, culminating in a standoff with then-FDA Commissioner Stephen Hahn, who dared his foes to fire him.
But while 2021 has undoubtedly been better, it has brought headaches of its own, including some of the FDA’s making.
In June, the agency approved a controversial Alzheimer’s drug called Aduhelm — despite many researchers saying there is insufficient data to show it works. The decision has sparked investigations by two congressional committees and the HHS inspector general. FDA officials, including Woodcock, have said they stand behind the approval, but even insiders acknowledge the process was messy and that the agency’s rationale raised many questions.
“It was an unforced error,” said Peter Lurie, who served as the FDA’s associate commissioner for public health strategy and analysis during the Obama administration and is president of the nonprofit Center for Science in the Public Interest.
And while the public haranguing of scientific agencies has abated under Biden, some parallels exist in how the Trump and Biden administrations have privately pushed the FDA to work faster.
“The same pressure that Democrats decried under Trump is happening now,” said an official who has worked with both administrations, speaking on the condition of anonymity to detail private conversations. That official described “a lot of leaning on” Woodcock, Marks and Patrizia Cavazzoni, who oversees drug approvals at the FDA, “to get things done.”
In mid-August, as concerns rose about breakthrough infections among the vaccinated, senior Biden administration health officials announced a plan to make booster shots available beginning the week of Sept. 20, pending FDA and CDC sign-offs. Among those who signed the statement were Woodcock; Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases; and CDC Director Rochelle Walensky.
Gruber and Krause felt boxed in by the statement and were especially upset that it included a specific target date for boosters, the former FDA official said.
Woodcock has said it was important to have a booster plan in place if the shots were needed. But she and Walensky later told the White House that only the Pfizer-BioNTech shot was close to being ready for possible approval, a rollback of the original plan.
Senior FDA officials deny they have been pressured by the White House. “I can tell you as the person who has been sitting there, people have not pressured us to make certain decisions, okay?” Marks said at the conference Monday. He and other senior officials, he said, have been pressing to speed up FDA actions because the United States is in a “war” with the virus.
But another federal official freely admits to sometimes prodding the vaccine officials, saying they can sometimes be too slow and methodical. “Of course there is pressure,” said the official who spoke on the condition of anonymity to describe internal conversations. “We are in a pandemic.”
Another big question: Who will be the next permanent commissioner at an agency that has endured almost constant leadership churn in recent years? Since spring 2015, when Margaret Hamburg, one of the longest-serving commissioners left, the agency has had seven leaders — three Senate-confirmed commissioners and four acting.
Woodcock, who was director of the FDA’s Center for Drug Evaluation and Research for decades, was thought to have the inside track to be nominated until Sen. Joe Manchin III (D-W.Va.) and some other Democratic senators expressed opposition, blaming her center for approving too many opioids and helping fuel the drug-overdose crisis.
Inside the agency, Woodcock wins praise for steering the agency during a tumultuous time and taking on unglamorous but important tasks such as overhauling dated computer systems.
Under federal law, the White House must nominate a permanent leader for the FDA by Nov. 15. If Woodcock is not nominated — and the odds seem against a nomination — she could continue to serve as the acting agency head while Biden’s nominee undergoes confirmation hearings.
Outside experts say they’re worried about the uncertainty hanging over the FDA, particularly with decisions looming on vaccines.
“Are we going to be in a situation in late October where the acting commissioner is on her way out, these two vaccine people are on their way out, and FDA is having to make some major decisions?” said Walid Gellad, the director of the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing.