It’s not the hottest ticket in town. The Prescription Drug User Fee Act (PDUFA) funds 42 percent of the budget of the Food and Drug Administration (FDA) Center for Drug Evaluation and Research, a large, complex, and indispensable scientific bureaucracy that requires fundamental stability. Since 1992, PDUFA has cut drug approval times in half. Congress is proud of it. The likelihood of dramatic change is slight.

But despite the bias toward the status quo, the mood was restless and prickly at an April 17 House Energy and Commerce hearing on PDUFA reauthorization. “We’re opening the door to a whole slew of issues,” California Democrat Lois Capps warned. The Senate Health, Education, Labor, and Pensions (HELP) Committee began its work on reauthorization the following day. The nominal deadline for reauthorization is September 30, but action is needed months earlier if layoffs and other disruptions at the FDA are to be avoided.

The crux of the criticism of PDUFA is that the user fees and the collaborative relationship they have engendered between the FDA and the pharmaceutical industry have undermined the agency’s ability to regulate Big Pharma independently. The issues, which echo concerns raised in last year’s Institute of Medicine report, The Future of Drug Safety, and in an earlier report by the Government Accountability Office, were expressed forcefully in an open letter to congressional leaders from a high-profile group of FDA critics in March of this year. The impending congressional debate was previewed further in three April 14 commentaries in the New England Journal of Medicine by Sean Hennessy, Jerry Avorn, and Mark McClellan.

Safety First

Critics are concerned that the FDA negotiates the terms of its PDUFA reauthorization proposal with representatives of the pharmaceutical industry behind closed doors, including the allocation of user-fee proceeds between the generously funded premarket approval process and underfunded postmarket surveillance. Research by Harvard’s Dan Carpenter shows an association between the act’s tight approval deadlines and postmarket safety problems, and assistant FDA commissioner Theresa Mullin acknowledged that postmarket adverse drug event reports have risen 65 percent in the past three years. But liberal lion John Dingell (D-MI), chair of the Energy and Commerce Committee, defended the FDA against the charge of succumbing to undue influence. “There’s no evidence of wrong-doing,” he said.

Setting aside conduct issues that may be ultimately subjective and unresolvable, the PDUFA deliberations are certain to be roiled by overarching questions about the adequacy of the FDA’s drug safety regime, which has suffered an unmistakable loss of public confidence in the wake of the Vioxx debacle and other postmarket misadventures. PDUFA funding for postmarket surveillance appears to be disproportionately small, whether the remedy sought is reallocation or additional support from the public fisc. The FDA’s proposed bill increases funds for postmarket surveillance, but only from 5 percent of user-fee revenues to 6.7 percent, according to Hennessy.

Additional drug safety legislation is in the works. Pressure on PDUFA will be contingent to some extent on the fate of safety initiatives in the bipartisan Kennedy-Enzi bill in the Senate and a parallel measure in the House sponsored by Democrats Henry Waxman (CA) and Ed Markey (MA) that create new regulatory mechanisms as well as new funding. And contentious provisions on biogenerics and direct-to-consumer advertising may attach to PDUFA reauthorization.

Watch for the May 8 release of a thematic issue of Health Affairs on managing benefits and risks in medical innovation, with a variety of articles on FDA policy and related subjects.

Tags: Pharma