The Food and Consumer Product Safety Authoritythe commissioner’s attempt to drastically shorten the assessment of medicinesfavorite of President Donald Trump’s administration is causing unrest throughout the agency, fueling concerns that the plan could conflict with legal, ethical and scientific standards long used to investigate the safety and effectiveness of new drugs.
Marty Makary’sprogram causes new anxiety andconfusion among the staffalrocked by layoffsbuyouts, andleadership changesaccording to seven current or recently departed staffers. The people spoke to The Associated Press on condition of anonymity because they were not authorized to discuss confidential agency matters.
Questions remain at the highest levels of the FDA about which officials have the legal authority to sign off on drugs approved under the FDA Commissioner’s National Priority Voucher Programthat promises approval within a month for drugs that support “American national interests.”
Traditionally, approval decisions have almost always been handled by FDA review scientists and their immediate supervisors, and not by the agency’s political appointees and senior leaders.
But drug reviewers say they have received little information about how the new program works. And some executives working on a long-awaited 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 an assessment within one to two months simply has no scientific precedent,” said Dr. Aaron Kesselheim, a professor at Harvard Medical School. “The FDA cannot conduct the same detailed review of a regular application within one to two months, and does not have the resources to do so.”
On Thursday, Reuters reported that FDA officials have delayed review of two drugs in the program, partly because of safety concerns, including the death of a patient taking one of the drugs.
Health and Human Services spokesman Andrew Nixon said the voucher program prioritizes “scientific assessment of the gold standard” and aims to deliver “meaningful and effective treatments and cures.”
The program remains popular in the White House, where price concessions announced by the Republican president have repeatedly been accompanied by FDA vouchers for drug makers who agree to lower their prices.
For example, when the White House announced that Eli Lilly And Novo Nordisk would lower their prices popular obesity drugsAccording to several people involved in the process, FDA officials had to scramble to obtain new vouchers for both companies in time for Trump’s press conference.
That has led to widespread concern that the FDA’s drug reviews — long tied to objective standards and procedures — have become open to political interference.
“It is extraordinary to have such an opaque application process, one that is clearly open to politicization,” said Paul Kim, a former FDA attorney who now works with pharmaceutical clients.
Top FDA officials refused to sign off on accelerated approvals
Many of the concerns surrounding the program stem from the fact that it is not codified in federal rules and regulations.
The FDA already has more than half a dozen programs in mind speed up or streamline assessments for promising drugs – all approved by Congress, with rules drawn up by agency staff.
Information about the voucher program, on the other hand, is usually limited to an agency’s website. Drug manufacturers can apply by submitting a 350-word ‘declaration of interest’.
More and more agency leaders such as Dr. Vinay Prasadthe top medical official and director of the FDA’s vaccine center, has reached out directly to drugmakers about awarding vouchers. That has created dilemmas for FDA officials, even on basic questions such as how to formally award a voucher to a company that hasn’t requested one.
Nixon, the HHS spokesman, said voucher submissions are reviewed by “a senior, multidisciplinary review committee” led by Prasad.
Questions about the program’s legality prompted the FDA’s then drug director Dr. George Tidmarshto refuse to sign approvals under the process, according to several people with direct knowledge of the matter. Tidmarsh resigned from the agency the following November a lawsuit against his behavior on issues unrelated to the voucher program.
After his departure, Dr. Sara Brenner, the FDA’s chief deputy commissioner, was given decision-making authority, but she also declined the role after further investigating the legal implications, the people said. Currently, the agency’s deputy chief medical officer, Dr. Mallika Mundkur, who works under Prasad, takes the responsibility.
Giving final approval to a drug carries significant legal risks, essentially declaring that the drug meets FDA standards for safety and effectiveness. If unexpected safety issues arise later, both the agency and individual staffers may be affected involved in investigations or lawsuits.
Traditionally, approval comes from FDA drug agency directors, in consultation with a team of reviewers. Approval under the voucher program will come via 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’s a complete turnaround from the normal review process, which is traditionally led by the scientists who delve into the data,” said Kesselheim, a lawyer and 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, could be short-lived because it isn’t codified.
“If you live by the press release, you die by the press release,” Troy said. “Anything they do now could be wiped out in the blink of an eye by the next administration.”
The voucher program has grown explosively after education from FDA officials
Initially set up as a pilot program with no more than five medications, it has expanded to 18 vouchers awarded, with more to be awarded. That puts additional pressure on the agency’s drug center, where 20% of staff have left in the past year due to retirements, takeovers or layoffs.
When Makary unveiled the program in October, there were immediate concerns about the unprecedented power he would have in deciding which companies would benefit.
Makary then said the drug nominations would come from career staffers. Some of the first drugs were even recommended by FDA reviewers, according to two people familiar with the process. They said FDA officials deliberately selected drugs that could be quickly vetted.
But selection decisions are increasingly guided by Prasad or other senior officials, sometimes without the knowledge of FDA staff, according to three people. In one case, FDA reviewers learned from this 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 conduct business, people familiar with the matter said, contrary to long-standing precedent.
Under pressure from drug makers, some FDA reviewers were told they could skip steps
Once a voucher is awarded, some drug manufacturers have their own interpretation of the review timeline, creating further confusion and anxiety among staff.
Two people involved in the ongoing assessment of Eli Lilly’s anti-obesity pill Company executives initially told the FDA they expected the drug to be approved within two months.
The timeline alarmed FDA reviewers because it did not include the agency’s standard 60-day prefiling period, during which staffers review the application to ensure no critical information is missing. That 60-day window has been in place for more than 30 years.
Lilly pushed for a faster filing and demanded a week. Ultimately, the agency and the company agreed on a two-week period.
Lilly’s CEO, David Ricks, told attendees at a healthcare conference Tuesday that the company expects FDA approval for its pill in the second quarter of the year.
Nixon declined to comment on the details of Lilly’s review, but said FDA reviewers “may adjust timelines as necessary.”
Employees were pressured to advance the application even though key data on the drug’s chemistry appeared to be missing, according to a 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 correct.
Former reviewers and outside experts say this approach is the opposite of how FDA reviews should work: By following regulations, staffers scientifically confirm the safety and effectiveness of drugs.
Skipping review steps could also pose risks to drugmakers if future FDA leaders decide a drug hasn’t been properly vetted. Like other experts, Kesselheim says the program may not last longer than the current administration.
“They fundamentally change 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.”
—By Matthew Perrone, AP Health Writer
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation. The AP is solely responsible for all content.
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