The FDA has been on a mission to speed up drug approvals. But this push to get new medicines to market faster is raising the stakes for smaller companies that may struggle to compete with Big Pharma in a quickly-shifting landscape.
The Commissioner’s National Priority Voucher pilot program, for example, allows certain drugs to move through the review and approval process in as little as two months, instead of the traditional 10. Draft guidance in February also outlined a new “plausible mechanism pathway” for niche drugs targeting tiny patient populations when randomized clinical trials aren’t feasible.
“There is [also] some talk about perhaps putting some of these things into the next PDUFA, which is being negotiated right now,” said Bill Holtz, a legal and regulatory strategist and of counsel with Foley & Lardner.
While some of these proposals are still in the early stages of planning, smaller companies that don’t have the same bandwidth or resources could be feeling the heat.
“There's pressure to do it better, quicker, sooner, faster to get their studies done, to try to utilize surrogate markers, for example, to not have to wait for certain other efficacy outcome variables to be done,” said David Rosen, a partner at Foley & Lardner.
And that pressure could lead to a cascade of challenges because smaller companies are typically less financially flexible, and there’s often no second shot at approval if the first filing fails.
“If they have to run a second trial it makes it much more difficult to raise money,” he said.
Upheaval at the FDA
The FDA has been quick to say accelerating approvals won’t mean cutting corners.
“None of these policy announcements purport to change the evidentiary standard for approval, which is substantial evidence of effectiveness,” Holtz said. “No one is saying we should be changing the quality of the evidence.”
But this push comes at a time when the FDA is already under unique strain, including large-scale workforce cuts across HHS and management changes in the upper levels of the agency.
“Staffing is certainly an issue,” Holtz said. “It was an issue prior to DOGE … [when] drug review teams were pretty much at capacity. And so it has certainly only gotten worse,” he said.
The agency’s current staff is not only under pressure to move quicker but to hit the right notes with leaders in an increasingly politicized environment, Rosen said.
“There are a lot of political appointees in leadership positions at FDA, and that's where a lot of these policies are coming from,” Holtz said. “We're seeing clients try to operate probably more politically than they have in the past.”
In this shifting environment, companies are talking to congressional staff and working behind the scenes to address issues or concerns they believe are inconsistent with public policy or not in the best interest of public health, Rosen said.
“We see some people doing a fair amount of talking and trying to at least have their points heard,” he said.
The frequent staff churn at the agencies has also raised uncertainty about policy announcements or draft guidance which might later be revised or abandoned.
Dr. Vinay Prasad, the FDA’s current director of the Center for Biologics Evaluation and Research, is set to step down at the end of April. His planned departure follows a series of high-profile controversies related to how CBER has conducted drug reviews under his tenure, including the decision to not review Moderna’s mRNA flu vaccine, which was later reversed amidst external pressure.
Navigating choppy waters
To ensure companies can accommodate this increased pressure, establishing regular ongoing communication with the FDA is becoming increasingly important, Holtz said. Keeping tabs on potential changes is also critical.
“Confirm the current advice is still the current advice [and] that folks haven't changed their minds on critical elements of your development program,” he added.
Laying out a detailed drug development plan and keeping careful documentation of meeting minutes are also necessary strategies.
“If there are changes in the administration or changes in the leadership and people want to add additional requirements, we have to look at those issues very carefully, because if it's necessary to demonstrate safety and effectiveness, that's one thing, but if it's somebody else just having a different difference of opinion, that's another,” Rosen said. “Companies should be able to rely on the advice they get from the FDA as they follow their drug development programs.”
Rosen said they’ve encountered situations where initial, outlined FDA requirements have changed as new people joined the review team. In instances where there is disagreement, negotiation is often successful.
What hasn't changed is that FDA staff are willing to work with companies.
“The staff at the FDA is definitely very dedicated. In the last six to nine months, we've had more communication with FDA than I've had in quite some time,” Rosen said. “So, they're trying to work very hard and to get things out and to communicate with the industry.”
