The Beginning of the End of the User Fee Era?

In the 15 years since the Prescription Drug User Fee program was created, the biopharma industry and its investors have gotten used to a once-unthinkable proposition--that FDA would give a clear yes or no answer about the approvability of a new drug by a tight deadline.

That record of reliability now may be in jeopardy.

Given the agency's ongoing resource problems, Office of New Drugs Director John Jenkins has given overworked and overwhelmed review divisions the green light to do what was once unthinkable: miss PDUFA deadlines.

According to a story in BioCentury this week, Jenkins’ unofficial and unpublicized directive could result in FDA missing more than 10% of user fee deadlines this year. That may not sound too bad, suggesting only a minor slippage from the agency's official commitment under the PDUFA agreement to meet its goals for at least 90% of its applications.

But in reality, FDA's track-record on meeting deadlines has been very close to 100%.

What Jenkins is describing is a limited number of missed deadlines—only in cases when a division feels overwhelmed by its workload. But once you start missing deadlines, it becomes very difficult to get caught up. And it's not like FDA is being overwhelmed by new drug applications these days. Imagine what might happen if new drug applications were streaming into FDA like they were 10 years ago.

For industry, the beautiful thing about the user fee process is its predictability: on new drug reviews, FDA promises to give a sponsor an answer by a certain date. And if company executives ask for a meeting with FDA officials to discuss an application, they know they will receive one within a set period of time.

Up until now, user fee activities have historically been considered sacred cows at FDA: industry fees have increased at a healthy clip at each reauthorization of PDUFA. It’s been all the “extraneous” activities funded through congressional appropriations—like professional development and, until recently, post-marketing safety—that have suffered due to a lack of funding.

And these days, it seems like FDA is stretched to the limit. Between the inspections debacle, the FDA Amendments Act implementation, and the new “Safety First” postmarketing safety initiative, FDA “has more work on our plate than we can possibly accomplish,” Jenkins told BioCentury. “We are having to prioritize. We are having to set aside some things, hopefully on a temporary basis, until we can get adequately staffed.”

But hiring and training new staffers is no easy process, thanks to a lengthy and arcane procedure under current HHS guidelines. Mary Pendergast, a former deputy associate commissioner at FDA, discussed this exact dilemma during Windhover's FDA/CMS Summit in December.

“The FDA has to hire many additional people. But as any FDAer would tell you, the new rules imposed by the Department of Health & Human Services—which took away from the FDA the ability to hire its own staff—has caused a very difficult time for the FDA in terms of making new hires,” she said. “The system is so long that most competent people will have found a new job by the time the FDA tells them they want them to be hired.”

So far, Congress has turned a deaf ear to FDA’s resources woes, wanting promises of an agency overhaul before appropriating any more money. Capitol Hill has sent a clear signal on where it believes FDA’s priorities should lie, and it’s not in faster review times.

Congress wants FDA to hold advisory committess for all new molecules, or justify a decision not to in writing. The logistics of scheduling committee reviews within six- or 10-month deadlines make that a tall order. And the decision to delay an advisory committee review for Theravance's televancin demonstrates the real-world consequences of placing safety concerns (in this case, the integrity of the trial data) over PDUFA deadlines.

Then there is the focus on the preapproval inspection process. When that program was created in 1990, the first impact was a delay in approval for a number of pending applications while the agency hustled to conduct inspections of the facilities. In the intervening years, FDA has developed a list of exceptions to the preapproval inspection policy--and Congress isn't happy about that. Another reason for delays.

The bottom line is that folks like Reps. Rosa Delauro and Bart Stupak or Sen. Chuck Grassley are less concerned about missing a few deadlines than when FDA inspects the wrong heparin facility in China. Indeed, they are clearly uncomfortable with the entire user fee model--a fact that should give the biopharma industry pause.