Legal questions swirl around FDA’s new expedited drug program, including who should sign off

WASHINGTON (AP) — The Food and Drug Administration commissioner’s effort to drastically shorten the review of drugs favored by President Donald Trump’s administration is causing alarm across the agency, stoking worries that the plan may run afoul of legal, ethical and scientific standards long used to vet the safety and effectiveness of new medicines.

Marty Makary’s program is causing new anxiety and confusion among staff already rocked by layoffs, buyouts and leadership upheavals, according to seven current or recently departed staffers. The people spoke to The Associated Press on the condition of anonymity because they were not authorized to discuss confidential agency matters.

At the highest levels of the FDA, questions remain about which officials have the legal authority to sign off on drugs cleared under the Commissioner’s National Priority Voucher program, which promises approval in as little as one month for medicines that support “U.S. national interests.”

Traditionally, approval decisions have nearly always been handled by FDA review scientists and their immediate supervisors, not the agency’s political appointees and senior leaders.

But drug reviewers say they’ve received little information about the new program’s workings. And some staffers working on a highly anticipated anti-obesity pill were recently told they can skip certain regulatory steps to meet top officials’ aggressive deadlines.

Outside experts point out that FDA drug reviews — which range from six to 10 months — are already the fastest in the world.

“The concept of doing a review in one to two months just does not have scientific precedent,” said Dr. Aaron Kesselheim, a professor at Harvard Medical School. “FDA cannot do the same detailed review that it does of a regular application in one to two months, and it doesn’t have the resources to do it.”

On Thursday Reuters reported that FDA officials have delayed the review of two drugs in the program, in part due to safety concerns, including the death of a patient taking one of the medications.

Health and Human Services spokesman Andrew Nixon said the voucher program prioritizes “gold standard scientific review” and aims to deliver “meaningful and effective treatments and cures.”

The program remains popular at the White House, where pricing concessions announced by the Republican president have repeatedly been accompanied by FDA vouchers for drugmakers that agree to cut their prices.

For instance, when the White House announced that Eli Lilly and Novo Nordisk would reduce prices on their popular obesity drugs, FDA staffers had to scramble to vet new vouchers for both companies in time for Trump’s news conference, according to multiple people involved in the process.

That’s sparked widespread concern that FDA drug reviews — long pegged to objective standards and procedures — have become open to political interference.

“It’s extraordinary to have such an opaque application process, one that is obviously susceptible to politicization,” said Paul Kim, a former FDA attorney who now works with pharmaceutical clients.

Many of the concerns around the program stem from the fact that it hasn’t been laid out in federal rules and regulations.

The FDA already has more than a half-dozen programs intended to speed up or streamline reviews for promising drugs — all approved by Congress, with regulations written by agency staff.

In contrast, information about the voucher program is mostly confined to an agency website. Drugmakers can apply by submitting a 350-word “statement of interest.”

Increasingly, agency leaders such as Dr. Vinay Prasad, the FDA’s top medical officer and vaccine center director, have been contacting drugmakers directly about awarding vouchers. That’s created quandaries for FDA staffers on even basic questions, such as how to formally award a voucher to a company that didn’t request one.

Nixon, the HHS spokesman, said that voucher submissions are evaluated by “a senior, multidisciplinary review committee,” led by Prasad.

Questions about the legality of the program led the FDA’s then-drug director, Dr. George Tidmarsh, to decline to sign off on approvals under the pathway, according to several people with direct knowledge of the matter. Tidmarsh resigned from the agency in November after a lawsuit challenging his conduct on issues unrelated to the voucher program.

After his departure, Dr. Sara Brenner, the FDA’s principal deputy commissioner, was set to have the power to decide, but she also declined the role after looking further into the legal implications, according to the people. Currently the agency’s deputy chief medical officer, Dr. Mallika Mundkur, who works under Prasad, is taking on the responsibility.

Giving final approval to a drug carries significant legal risks, essentially certifying that the medicine meets FDA standards for safety and effectiveness. If unexpected safety problems later emerge, both the agency and individual staffers could be pulled into investigations or lawsuits.

Traditionally, approval comes from FDA drug office directors, made in consultation with a team of reviewers. Under the voucher program, approval comes through a committee vote by senior agency leaders led by Prasad, according to multiple people familiar with the process. Staff reviewers don’t get a vote.

“It is a complete reversal from the normal review process, which is traditionally led by the scientists who are the ones immersed in the data,” said Kesselheim, who is a lawyer and a medical researcher.

Not everyone sees problems with the program. Dan Troy, the FDA’s top lawyer under President George W. Bush, a Republican, says federal law gives the commissioner broad discretion to reorganize the handling of drug reviews.

Still, he says, the voucher program, like many of Makary’s initiatives, may be short-lived because it isn’t codified.

“If you live by the press release then you die by the press release,” Troy said. “Anything that they’re doing now could be wiped out in a moment by the next administration.”

Initially framed as a pilot program of no more than five drugs, it has expanded to 18 vouchers awarded, with more under consideration. That puts extra pressure on the agency’s drug center, where 20% of the staff has left through retirements, buyouts or resignations over the past year.

When Makary unveiled the program in October there were immediate concerns about the unprecedented power he would have in deciding which companies benefit.

Makary then said that nominations for drugs would come from career staffers. Indeed, some of the early drugs were recommended by FDA reviewers, according to two people familiar with the process. They said FDA staffers deliberately selected drugs that could be vetted quickly.

But, increasingly, selection decisions are led by Prasad or other senior officials, sometimes unbeknownst to FDA staff, according to three people. In one case, FDA reviewers learned from GlaxoSmithKline representatives that Prasad had contacted the company about a voucher.

Access to Makary is limited because he does not use a government email account to do business, according to people familiar with the matter, breaking with longstanding precedent.

Once a voucher is awarded, some drugmakers have their own interpretation of the review timeline — creating further confusion and anxiety among staff.

Two people involved in the ongoing review of Eli Lilly’s anti-obesity pill said company executives initially told the FDA they expected the drug approved within two months.

The timeline alarmed FDA reviewers because it did not include the agency’s standard 60-day prefiling period, when staffers check the application to ensure it isn’t missing essential information. That 60-day window has been in place for more than 30 years.

Lilly pushed for a quicker filing turnaround, demanding one week. Eventually the agency and the company agreed to a two-week period.

Lilly’s CEO, David Ricks, told attendees at a health care conference on Tuesday that the company expects FDA approval of its pill in the second quarter of the year.

Nixon declined to comment on the specifics of Lilly’s review but said FDA reviewers can “adjust timelines as needed.”

Staffers were pushed to keep the application moving forward, even though key pieces of data about the drug’s chemistry appeared to be missing, according to one person involved in the process. When reviewers raised concerns about gaps in the application, the person said, they were told by a senior FDA official that it was OK to overlook the regulations if the science is sound.

Former reviewers and outside experts say that approach is the opposite of how FDA reviews should work: By following the regulations, staffers scientifically confirm the safety and effectiveness of drugs.

Skipping review steps could also carry risks for drugmakers if future FDA leaders decide a drug wasn’t properly vetted. Like other experts, Kesselheim says the program may not last beyond the current administration.

“They are fundamentally changing the application of the standards, but the underlying law remains what it is,” he said. “The hope is that one day we will return to these scientifically sound, legally sound principles.”

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