The New Flavor of PDUFA
by Adam Istas
September 2007
While enhancing post-marketing safety surveillance of pharmaceutical products is a legislative concern in the United States, many wonder whether the various drug safety initiatives go far enough.
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Prescription drug safety has taken a legislative front seat in the United States in 2007. While considering and debating the Food and Drug Administration Revitalization Act (FDARA), the U.S. Congress also has been deciding the fate of the soon-to-expire Prescription Drug User Fee Act (PDUFA). First established in 1992 as a way to decrease review times for new drugs, the user fee program—in which drug manufacturers pay the FDA to review new drug applications—now contains additional resources and funding for multiple post-marketing drug safety programs. Approved by the Senate in May 2007, the entire FDARA package is a massive, wide-ranging piece of legislation that, among other things, will strengthen the FDA’s authority for monitoring the safety of drugs already on the market.
In its original proposal to Congress in March, the FDA requested an additional US$29.3 million to enhance the agency’s drug safety capabilities. Primarily designed to increase staffing levels to perform post-marketing safety surveillance, the additional funds also are intended to provide safety surveillance for drugs as long as they remain on the market. The extended monitoring would require the elimination of a provision from earlier PDUFA renewals that limited user fees to only the first three years following a drug’s approval. Although the amount of money specifically requested for adverse-event surveillance amounts to about 6.7 percent of user fees the agency anticipates to collect, several critics have decried the amount as being far short of what is required to make a noticeable difference in the U.S. drug safety system.
In an April 26, 2007 column in the New England Journal of Medicine (NEJM), Sean Hennessy, Ph.D., and Dr. Brian Strom of the University of Pennsylvania School of Medicine contend that “although the activities it proposes are all worthwhile, the agency’s overall plan will fall far short of the goal of modernizing and transforming the drug-safety system.” Harvard Medical School’s Dr. Jerry Avorn and former FDA commissioner Dr. Mark McClellan in the same issue of NEJM agree. Despite the concerns, however, the drug safety initiatives included in FDARA may lead to a substantial change in the manner in which post-marketing research is conducted.
“The current system of adverse drug reporting captures less than 10 percent of actual events,” says Doug Peddicord, Ph.D., executive director of the Association of Clinical Research Organizations (ACRO), in Washington, D.C., USA. “And there’s clear agreement from the FDA as well as from manufacturers and their CRO partners that the system needs to be improved.”
Peddicord says that the entire legislative package has in fact been greatly enhanced since the FDA originally submitted it to Congress; particularly with regard to the risk evaluation and mitigation strategies (REMS) outlined in FDARA. “The legislative package was improved by essentially giving the agency some new authorities in terms of post-approval, but also some flexibility in the application of those authorities,” he says.
Among the changes to FDARA with regard to REMS, the sponsoring senators, Democrat Edward Kennedy from Massachusetts and Republican Mike Enzi from Wyoming reduced the REMS requirement to only those drugs known to present high risk. This moderated version was finalized in May 2007, just before the bill moved from the Senate to the House. Various other prescription drug issues—notably reimportation and a renewal of pediatric exclusivity provisions—also are addressed in the final bill.
But perhaps the largest change that may come out of the FDARA/PDUFA legislation is the strengthened post-marketing powers of the FDA. Much of the additional funding for increased safety programs is aimed at developing and implementing electronic information systems for collecting and monitoring adverse events; a task that will require not only additional funding and additional staffing, but also additional cooperative agreements with pharmaceutical manufacturers and clinical research organizations to adequately manage a more robust surveillance system. Furthermore, extending the FDA’s power to oversee a drug throughout its entire lifecycle—through provisions calling for easier label changes and giving the agency more teeth to enforce post-marketing studies—the agency will essentially become a post-marketing safety watchdog as opposed to one primarily concerned with pre-approval testing and controls.
“One of the things that Congress is trying to do is improve public confidence in what is in fact the most effective regulatory system and the safest medical product market in the world,” Peddicord says. “The impact will be to increase confidence in the agency by the public, hopefully the media, as well as physicians and prescribers.”
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