The agency has been in the spotlight because of the pandemic, questions about its independence and the approval of Aduhelm. The stakes are high and the politics, fraught.
Ten months into the Biden administration and no one has been nominated to be the permanent FDA commissioner, let alone confirmed. The void reflects the high stakes involved in the position and the bramble of political tensions that have engulfed the federal regulatory agency. But those are some of the very same reasons the agency needs someone at the helm, say many observers and people in the industries that the FDA regulates. “All nominations to healthcare agencies are essential during the global public health crisis. They’re essential all the time, but even more so during this period,” says Alec Stone, public affairs director of the Oncology Nursing Society.
Mid-October, an apparent front-runner for the nomination seemed to emerge. Numerous news outlets reported that President Biden was getting ready to nominate Robert Califf, M.D., MACC. Califf would appear to be a relatively safe choice; he was one of the FDA commissioners during the Obama administration. But as we went to press, there was still was no official announcement, so uncertainty about who would be running the FDA lingered.
Janet Woodcock, M.D., has been the acting commissioner since Biden’s inauguration at the beginning of this year. Woodcock, who has worked at the agency for 35 years, was once considered among the finalists for nomination to be the permanent commissioner. Her backers credited her with speeding up the FDA’s drug approval process and getting more therapies approved, particularly cancer treatments. Her detractors flipped the script and accused her of lowering FDA standards and allowing questionable drugs on the market. Sen. Joe Manchin, among others, cast blame for the opioid epidemic on Woodcock.
“The FDA has played a critical role in this overdose epidemic by overseeing continuous approvals of stronger and more addictive opioids since the initial approval of OxyContin in 1995 — and Dr. Woodcock has been there for all of it,” Manchin wrote in an open letter in June. The agency’s controversial approval of Aduhelm (aducanumab) for treatment of Alzheimer’s disease also possibly worked against Woodcock. Numerous media outlets reported in mid-August that the White House had decided against nominating her. “There have been little hiccups along the way, and everything is political,” Stone says. “I don’t think anyone is suggesting she’s not qualified and experienced.”
Technically, Woodcock was allowed to serve as acting commissioner for a period of just 210 days, which ended in mid-August. But the Federal Vacancies Reform Act of 1998 allows an additional 90 days of service if the vacancy existed at inauguration or became vacant in the 60 days following inauguration. That 90-day period ends Nov. 15. The clock restarts, though, if and when the Biden administration nominates a candidate for the permanent job, which would give Woodcock another 210 days until that nominee is confirmed, withdrawn, returned or rejected.
Politics as unusual
There are exceptions, such as Scott Gottlieb, M.D., and David Kessler, M.D., but throughout much of the FDA’s 115-year history, most of its commissioners have kept a relatively low profile. The pandemic changed that. Questions about whether the agency caved to pressure from the Trump administration clouded Stephen Hahn’s tenure as commissioner. The agency approved and then revoked an emergency use authorization for hydroxychloroquine, the antimalarial drug that former President Donald Trump promoted as treatment for COVID-19. Hahn also ended up apologizing for mischaracterizing the effectiveness of convalescent plasmas as treatment for the disease.
“It’s been an unusual Washington parlor game,” Stone says of the people who argued for or against Woodcock. Califf would be a “very solid choice,” in Stone’s view. He is familiar with the agency and having served in the Obama Administration means that he and Biden likely have a good working relationship, Stone says.
The FDA is probably best known for regulating drugs and vaccines, but it also has regulatory oversight of much of the food, cosmetics, medical device and tobacco products industries. By the agency’s own reckoning, FDA-regulated products account for about one-fifth of annual spending by U.S. consumers, which works out to be roughly $2.8 trillion.
How the agency wields its powers has changed over the years. Decades ago, the FDA was more of a policing organization to protect the public from potentially harmful drugs, says Sharon Ayd, Ph.D., MBA, an industry consultant. In the 1960s, Frances Oldham Kelsey, an FDA reviewer, was responsible for keeping thalidomide, a morning sickness drug that caused birth defects, off the market in the U.S.
But the agency started to work more closely with the pharmaceutical industry in the early 1990s partly because of the 1992 Prescription Drug User Fee Act, which, among other changes, set up a system of industry fees to support the agency’s drug approval process in exchange for speeding up that process and setting deadlines.
Ayd credits Gottlieb, who was commissioner from 2017 to 2019, with bringing more change to the agency by fostering a constructive working relationship with drug developers. FDA officials now start talking and working with drug discovery companies earlier. The culture of remaining open to new ideas and science continues, she says, “and that’s a great thing.” The FDA now allows practices that it once frowned upon if not prohibited, such as allowing some compounds to go into patients earlier for dose-escalation studies and companies to use surrogate markers to prove effectiveness. And with adaptive clinical trial design, trials can happen in parallel with FDA data review.
“That’s why Operation Warp Speed was possible,” Ayd says. Otherwise, developing a vaccine can take up to 30 years and still not be effective. “But the reason it worked was because the red tape got taken away, and the government, from the president’s office and probably from the head of the FDA, said ‘Don’t worry about making a mistake.’ But other than a pandemic, we always worry about making mistakes.”
But the approval of Biogen’s Aduhelm is seen by many as evidence that the agency has become too accommodating of drug developers and permissive in its approvals. Aaron Kesselheim, M.D., J.D., M.P.H., a professor at Harvard Medical School and director of the Program On Regulation, Therapeutics, And Law at Brigham and Women’s Hospital in Boston, called the Aduhelm approval “probably the worst drug approval decision in recent U.S. history” in his resignation letter from the advisory committee that had recommended against approval.
Stat reported on a history of unusual contact between FDA and Biogen officials when Aduhelm was foundering. After the approval, Woodcock requested an investigation from the U.S. Department of Health & Human Services’ Office of Inspector General, citing concerns about those contacts.
But the FDA and its commissioners are not exactly strangers to politics and controversy. Kessler, for example, was pilloried for promoting a “nanny state” because of steps he took to regulate the food and tobacco industries and by AIDS activists for not pushing the agency to approve drugs faster.
Ned Sharpless, M.D., director of the National Cancer Institute, served as acting commissioner for six months and was touted as a successor to Gottlieb instead of Hahn, but it was widely reported that the Trump White House crossed him off the list partly because he had contributed to the campaigns of Democrats. Gottlieb faced criticism for taking a tough stance on vaping.
Nor is the lack of permanent leadership without precedent. During the George W. Bush administration, the agency was headed by a series of interim commissioners for the better part of two years. “A continuous ‘interim director’ at FDA is like a babysitter left in charge of the children indefinitely — you don’t want to leave important decisions to that person,” said an influential congressman at the time.
“The FDA and professionals who work there have their goals and missions in their respective centers, promoting safety and efficacy,” says Stone. That said, a permanent commissioner would help solidify the agency’s priorities and long-term agenda. Those outside the agency are worried about the long-term agenda. “This is a major appointment in the healthcare environment, and many provider and advocacy groups are looking forward to a permanent commissioner. It’s not about tomorrow. It’s about next year,” Stone says.
Obviously, Biden officials want a nominee with enough votes in the Senate to win confirmation, so Manchin and a handful of other senators have more leverage. “In a 50-50 Senate, finding a nominee who will garner bipartisan support is the goal, even required,” notes Stone. Califf might fit the bill. He was a low-key FDA commissoner during the Obama administration and was in the job for just 11 months.
The FDA commissioner’s job is to walk that fine line between following the evidence and staying independent while being attuned to time constraints, stakeholder concerns and, yes, politics and public attitudes. With social media and a 24-hour news cycle, “it’s easy to pick up on anything and sensationalize it,” Stone says. “There are more hurdles today, more eyes watching. There’s a balance between what they need to do and what they’re being pushed to do from the outside, whether approving drugs faster or slowing down the process because we’re not sure what the evidence is.”
Plus, the pandemic has brought to the surface beliefs and attitudes that dismiss science and conventional medicine. As an agency that depends on science and evidence, the FDA and its commissioner may need to combat those formerly fringe ideas.
“There’s a bit of a disconnect with the American public in understanding the roles of agencies with oversight,” says Stone.
Deborah Abrams Kaplan writes about medical and practice management topics.