FDA job cuts hinder drug safety monitoring

US Food and Drug Administration layoffs appear to be affecting programs that track drug safety. Fired workers from the Division of Drug Information, which conducts safety monitoring, say the DDI team lost between 75% and 90% of its roughly 50-person staff in the FDA’s April 1 reduction in force.

“There’s a handful of people desperately keeping the lights on,” says one fired employee, who like their former colleagues spoke to C&EN on condition of anonymity for fear of repercussions.

The office once acted as a first point of contact for safety concerns from consumers, doctors, pharmacists, and industry whistleblowers, these fired staffers say—along with fielding a potpourri of other safety- and access-related requests from the public.

The cuts have caused confusion among health-care providers over at least two programs that had ensured pregnant patients would not be prescribed drugs that can cause birth defects. Brian Spoelhof, a pharmacist and bioethicist at an academic medical center whose views he does not represent, says that in mid-April he learned that risk evaluation and management programs for the drugs macitentan and ambrisentan had ended a week earlier.

Those drugs block receptors for endothelin peptide hormones. They are prescribed to treat pulmonary arterial hypertension, but if the drugs are taken during pregnancy, they can harm the embryo or fetus. To mitigate that risk, the FDA approved the drugs on the condition that anyone who prescribed, dispensed, or planned to take them had to enroll in a risk mitigation, or REMS, program.

The FDA oversees REMS programs, but they are administered and paid for by drug manufacturers. The one that applies to the endothelin receptor antagonists requires doctors to inform patients who could become pregnant about the risk from the drug, advise them on contraception plans, and make sure that patients are not pregnant before writing the prescription. The programs also involve a database that pharmacists can use to make sure doctors are licensed to make the prescription and that patients have enrolled.

Surprise program terminations

An email sent from the ambrisentan REMS program late on April 10 informed Spoelhof that the program had been discontinued on April 4 because the FDA had determined that the program “is no longer necessary to ensure the benefits of the drug outweigh the risk of embryo-fetal toxicity.” The program’s website has since been updated to reflect this decision.

Oddly, Spoelhof says, although there are at least three drugs in the endothelin receptor antagonist class, he’s received notice of termination for only two REMS programs. He phoned the program administrator to inquire about the third drug, bosentan.

“They had a script that was like, Yeah, we are hearing it from everybody. We still don't know whether ours is an enforcement or not, but we are acting as if it is because we haven't heard from the FDA otherwise,” Spoelhof tells C&EN. An FDA website still lists all three programs as active as of April 30.

Normally, according to the fired FDA employees who spoke to C&EN, after a clinical review team decides that a REMS program can end, the DDI would communicate that decision.

That FDA registry currently lists 77 active REMS programs, including those for the three endothelin receptor antagonist drugs. C&EN contacted 14 manufacturers of other drugs to ask for updates. Four responded to say that their programs are still active; one of those four manufacturers referred C&EN to a relaxation in program requirements that it announced by press release in mid-April.

C&EN emailed the DDI to try to establish the status of additional REMS programs and received an autoresponse warning that response times may vary “due to the HHS restructuring, effective April 1, 2025.” A subsequent email referred C&EN to the deputy press secretary for the US Department of Health and Human Services, Emily Hilliard, who did not respond to a detailed list of questions.

Outlook unclear

The new FDA commissioner Marty Makary has stated his interest in boosting safety monitoring. During his first sit-down interview as commissioner, on April 17, Makary told former Fox News reporter Megyn Kelly that “when you don’t have good postapproval monitoring, as this agency has not had, you discover things decades later.”

In the interview, which analysts have scrutinized for clues about the future of FDA policies, Makary discussed a vision for heightened oversight after drugs become commercially available, so that safety issues could be revealed more rapidly.

But laid-off staff say the DDI conducted exactly such safety monitoring. According to them, the remaining staff are scrambling to keep up with inquiries and have no capacity to update databases such as the REMS program registry.

The DDI is also responsible for publicizing drug product recalls, fielding doctors’ requests for special permission to give not-yet-approved drugs to individual patients as a last resort, and collecting data through MedWatch, a mechanism for reporting adverse events caused by drugs or raising concerns about contamination, such as widely-publicized issues of nitrosamine impurities in medications. The program is an early-warning system for potential problems, Spoelhof says, and its data collection has often led to recalls.

“Every single prescription medication that’s dispensed in the US has the MedWatch phone number on it,” one fired DDI staffer says, adding that the office handled about 42,000 phone calls and 30,000 emails from the public last year.

The HHS did not respond to inquiries about whether MedWatch is still operational. But the former employees who spoke to C&EN say that if a new safety or supply issue should arise, the system may be unable to cope.

Struggling to find information

Sphoelhof says the end of the REMS program for the endothelin receptor antagonists does remove a safeguard but also removes a barrier to access for some patients. For example, a REMS program for the schizophrenia drug clozapine was terminated last fall after an advisory committee called it overly burdensome for patients. Similarly, providers of reproductive health care have argued in court that a program regulating mifepristone raises barriers to timely abortion care.

Spoelhof is more concerned about how difficult it has been for him and colleagues to get clear information about which restrictions on prescribers are being enforced and which FDA programs are still active or not. “Where we’re kind of struggling is how to find . . . just any information,” he says.

“I think the thing is that a lot of the changes haven’t yet made [their] way down to the front line,” Spoelhof says. “But it’s certainly causing a lot of anxiety.”

As for the prescribing of macitentan and ambrisentan, Spoelhof says the doctors who treat pulmonary hypertension are generally highly trained specialists who won’t overlook the risks.

Still, “that pulmonary hypertension doctor isn’t always the one that’s on call,” and he worries that a less experienced trainee physician could write a prescription in error. He and his colleagues plan to continue to exercise due diligence with these drugs.