Is FDA Too Lax With its Drug Approval Standards? Senior FDA Officials Discuss

From industry to academia, commenters have argued that the US Food and Drug Administration’s (FDA) drug approval standards are becoming inappropriately low and that the required postapproval evaluations are either inadequate or left undone.

But three senior FDA officials offered several counterpoints on Monday at the fifth annual Biopharma Congress in Washington, DC.

Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, explained that the agency is working on its own analyses to provide “a more robust response” to these critiques. She also explained how the high number of approvals in recent years for rare diseases may be influencing this perception of a lower bar, especially as more treatments are approved on the basis of a single-arm study or with an external control group. In addition, she pointed to the “astoundingly” high launch prices for some of these rare disease treatments that may also be part of the reason for the pushback.

“We can’t opine on [prices] but we need to get the facts and figures together on the trajectories of what they were and what they are now,” Woodcock said, noting she does not think there are any concerns from FDA staff related to therapies approved with a breakthrough or other accelerated designation.

Peter Marks, director of FDA’s Center for Biologics Evaluation and Research (CBER), said he thinks FDA will “always be criticized for being too fast or too slow,” and that he’s “trying to strike the right balance.” He said it’s been helpful that with some gene therapies, “it’s very clear that the outcomes are very apparent, but the problem is that many are not that clear.”

He also said that with some regenerative medicine products, CBER sees the opposite extreme as the “therapies that are not effective and they want us to say they are effective.” When FDA says a product has the appropriate efficacy and safety, “we want people to put appropriately placed hope in those products,” he added.

But Marks cautioned: “If there’s no efficacy, nothing is safe enough,” referring to some regenerative medicine products that patients are being charged for but which are ineffective.

He also said FDA may get it wrong occasionally with an approval, echoing comments made by Acting Commissioner Ned Sharpless at lunch with regard to accelerated approvals, but Marks added: “That’s what happens when you’re working at the edge.”

Gideon Blumenthal, deputy director of FDA’s Office of Oncology Excellence (OCE), added that overall survival “is the gold standard endpoint” for oncology drugs, and “that’s what we always want to attain but there are circumstances where patient populations are getting smaller and smaller, and it would be impossible to detect overall survival.”

Marks also said that the largest development he’s seen recently is a transition from personalized to individualized medicine.

“We’re understanding the molecular mechanisms of disease and various individual characteristics of disease that we can target products for,” he said, which means a “unique approach to regulation because it’s not making products for traditional clinical development. It’s a different paradigm to find ways to have a prototype product supplemented with small changes, or for some products they won’t even be licensed but be perpetually under an IND.”

Marks also discussed how the pace of innovation right now “is incredibly fast – we have to be on top of what’s going on at industry, academic organizations and industry organizations. Our research teams are going through a horizon scanning process to continually retool with questions,” he added.

But Marks also noted that CBER is going to need to quickly increase in size to keep up with the pace of new submissions. FDA officials have previously said that by 2025, the agency will be approving between 10 and 20 cell and gene therapy products annually.

“We’re lucky to have attracted some skilled people, committed to gene and cell therapy, but it remains a challenge particularly with this growth. I wouldn’t be surprised if the cell and gene therapy branches need to double in size over the next three to five years,” Marks said.