Marty Makary’s FDA appears to be struggling on several fronts. It’s not surprising but comes with big risks for the agency and country.
Think of the departures of Peter Marks, Nicole Verdun, Celia Witten, and many others like staff scientists, physicians, and attorneys. Huge numbers of key support staff, who help make the wheels turn at the agency, are also gone.
You need thousands of experienced people to run such a complex government agency run even semi-normally, and the FDA just doesn’t have them anymore. I don’t see how it can function without some kind of major re-hire of experienced people. That’s not likely to happen.
Making matters worse, morale reportedly is so low that more people are heading for the exits. Those who remain are under major stress. Politics hold sway and experts inside the agency are often not consulted or are overruled.
This chaos has serious implications for the cell and gene therapy field.
Makary’s FDA is a skeleton crew
Makary and CBER leader Vinay Prasad (who now wears multiple FDA hats) can’t wave some magic wands and just make things better. You can’t just wing it with 3,500 fewer FDA employees. Having one person do three jobs (admittedly not so unusual in academia) doesn’t work great.
The Tweet below from Makary just last week seems quite inaccurate on FDA scientific reviewers being RIF’d.
Part of the frustrating irony here is that Makary’s new FDA National Priority Vouchers program is supposed to make some decisions faster, but the agency as a whole seems overall to be in slow motion in many ways.
A recent STAT piece highlighted the FDA’s woes under the new administration: Inside the staff exodus and tanking morale that threaten Makary’s FDA.
It paints a troubling picture of just how badly specific things have deteriorated at the FDA in recent months. However, it was the overall gestalt of agency dysfunction that worried me the most.
Both too slow and too fast?
Practically speaking, what are the risks of all these FDA issues?
Emerging new drugs, maybe including cell therapies, that warrant approval may not get it because of politics or internal chaos. At a minimum, many decisions will be delayed substantially.
Conversely, we’re likely going to see drug approvals, including of cell therapies, that are not justified. These will occur because of politics and a lack of FDA experts to review them properly.
Things are going to get very chaotic.
Lack of needed experience and leadership
Do Makary and Prasad have the kind of experience we would hope to see in top FDA leaders?
FDA Commissioner Scott Gottlieb under Trump 1.0 had far more FDA experience than the current leaders (both had zero before). He also didn’t dismantle the agency or stand by while someone else did. I didn’t see signs of him playing toxic political games either.
The report that Makary recently sought to retaliate against a sponsor for their comments (which HHS denies) is a big red flag:
“Then, a few weeks ago, Makary tried to push regulators to reject a rare disease drug from KalVista Pharmaceuticals after the company announced the FDA missed a review deadline due to “limited resources,” according to two sources familiar with the matter.”
So now sponsors can’t even mention delays? And if they do, they risk retaliation? That’s deeply concerning for the biotech sector.
Things are going to get worse
Again, maybe Makary and Prasad could shift things in a better direction if they brought back some of the lost staff, but there’s no sign that will happen.
These days, there’s also some misguided idea within agency leadership that it can get by on AI rather than experienced humans. You can’t use AI or some newbie (who happens to have the right politics but lacks biomedical chops) to replace FDA veterans.
Say, for whatever reason that I can’t imagine, you as someone doing a clinical trial on biologics like stem cells didn’t particularly care for Marks or Verdun or some of the other key leaders in biologics who are now gone, you still have to face the reality there’s just no sign now of them be replaced with equally experienced and effective leaders. The CBER organizational chart is like Swiss cheese.
Looking ahead, more things will inevitably slip through the cracks as the wonderful Holly Fernandez Lynch warned in the STAT piece. That will translate into all kinds of problems for the public and the country.
Your argument supposes that the agency had the optimal number of employees in January 2025. Maybe this is true, but I don’t see evidence for that supposition.
FDA prior to Makary certainly approved drugs with marginal or no net benefit. Remember Aduhelm?
@Peter, Yes, who knows what the optimal staffing of the FDA is? However, I’m pretty sure it didn’t need to lose 3,500 employees to get better including arguably many of the most experienced staff and leaders. I know CBER lost so many key people. This is especially risky when Prasad and Makary had zero previous FDA experience.
In the end, it’s really going to come down to how the FDA functions.
Cracks are already apparent but maybe the team will surprise us and keep it together. I’m skeptical that’s going to happen.
There are so many pressures on the FDA and urgent matters.
CBER alone gets 100s of IND applications a year, maybe close to a thousand in some recent years. They all have to be analyzed on a 30-day deadline. One source said 777 IND applications came to CBER in FY2021.
Moving forward it’s very possible that we’ll see a vast number of IND holds not based on biomedical concerns but just because CBER doesn’t have the bandwidth to review them properly. This is also one area where some things may slip through the cracks because the default mode is an IND is cleared after 30 days.
Actually, FDA doesn’t have to take any action on a filed IND. The regulations say that if FDA does not object, clinical trials may start 30 days after receipt of the IND submission. So the FDA’s lack of action on an IND tells us nothing about the state of affairs at the agency.
@Paul,
Excellent point. Unless the FDA’s computer systems are down or something, this comment on an IND submission may not tell us much.
From the perspective of someone who just filed an IND in cell therapy, 15 days ago it seems like the FDA is still working efficiently…anyone else have recent experience?
Thomas Ichim
Maybe that’s encouraging that the wheels are still turning.
But is the problem what’s happening *right now* with the FDA, or what’s going to happen in the coming weeks, months, and years? Because it seems like the issues are going to emerge more and more in the future rather than being immediately visible in the current snapshot of time.
Hi Inga, I think it’s both, but you’re right that things are likely to get progressively worse.
One of the biggest likely problems has nothing to do with politics or one’s views on FDA oversight of particular biologics, etc. and has already manifested in some cases. It’s just that the agency including CBER are likely to be increasingly slow with many decisions, reviews, and so forth.
Then in some rarer cases they might be too fast such as with certain approvals because the internal review of a particular investigational drug will not be thorough, there’s not enough experts left, they use AI in place of people, etc. and/or politics comes into play.