Monitoring Drug Recall: Enhancing the Postmarket Safety System

In 1992, the Food and Drug Administration (FDA) implemented the Prescription Drug User Fee Act (PDUFA). According to the Act, funding for the FDA’s drug approval process would come directly from the pharmaceutical industry. More specifically, the act mandated that drug manufacturers pay a substantial fee for each New Drug Application (NDA) they wanted reviewed. In recompense, the FDA was bound to review the application within a given amount of time. Congress has reviewed and re-passed the act on three separate occasions (1997, 2002, 2007) since its ratification. Yet despite congressional support, PDUFA is the subject of much controversy.

Many, including those within the Administration, feel that the FDA should maintain a healthy antagonism toward the pharmaceutical industry, and that industry funding for FDA research offsets the balance of power between the two sides. These concerns are not unfounded. The pharmaceutical industry has undoubtedly gained leverage over the FDA through PDUFA. But given the current economic climate, there are few other practical funding options. With that in mind, Congress should aim to allocate a larger portion of the New Drug Application fee to the postmarket drug safety system, thereby ensuring that if a drug with harmful side effects does manage to slip through the review process safety net, the FDA recall will be quick and efficient.

The FDA is in dire need of funding. According to the 1991 final report compiled by the Advisory Committee on the FDA, “Grave resource limitations impose sometimes staggering burdens on the Agency.”[1] The Institute of medicine went so far as to say that the administration was “begging for resources to do its job.”[2] This should never be the case with a program whose primary function is protecting the health of the American people.

PDUFA has undoubtedly helped reduce the funding problem. According to a study conducted by the School of Public Health and Health Services at George Washington University, “In FY 2006, PDUFA funds accounted for 42.5 percent of FDA’s total human drug program budget of $521 million (and for more than half the funds dedicated specifically to drug review).”[3] Since its inception in 1992, the act has helped increase the size of the FDA’s application review staff; as a result, the median review time for standard new drugs has decreased from 27 months in 1993, to 10.5 months in 2004.[4]  Unfortunately, when reviewing long-term drug side effects, speed and quality are not synonymous. As previously mentioned, under PDUFA the FDA is provided deadlines for its response to each NDA. Studies have shown that those drugs approved within the days and weeks closest to PDUFA deadlines are more likely to undergo labeling revisions and FDA recall.[5] One concludes then that pressure created by deadlines affects review quality.

In 2004, pharmaceutical giant Merck pulled its leading arthritis medication, Vioxx, from market. Postmarket studies found that the drug, approved as safe and effective by the FDA in May of 1999, significantly increased the risk of heart related side effects. At the time of its withdrawal, the drug had been prescribed to more than 84 million people worldwide.[6] Though perhaps the most publicized, the Vioxx incident is far from the only such instance of a faulty drug reaching the market. Another pharmaceutical powerhouse, The Warner Lambert Company, fabricated tests results so as to push three of their drugs through the NDA process. Amongst the drugs passed was Dilantin, an antiepileptic known to increase suicide risk in users. Clearly, pharmaceutical industry pressure affects the efficacy and reliability of the drug review process.

And yet, some maintain that the pharmaceutical industry’s interests are in line with those of the FDA. If drug companies push to release unsafe drugs, PDUFA advocates say, those companies will inevitably face consequences when their respective drugs face FDA recall. Pharmaceutical industry advocacy groups such as the Pharmaceutical Research and Manufacturers of America (PhRMA) argue vehemently against the repeal of PDUFA. In a 2006 press release, PhRMA stated, “fewer than three percent of approved prescription drugs have been withdrawn from the market for safety reasons over the last twenty years.”[7]—citing this statistic as proof that the industry had not abused its aforementioned leverage.

Anyone with a healthy amount of skepticism will see the fragility of these statistics, however. Assuming the approval of only 18 New Molecular Entities (NME) per year (this, the number of NMEs approved in 2006, was the lowest in a decade[8]), there are 360 NMEs approved every 20 years. If three percent of these NMEs are recalled, that’s nearly eleven drugs with harmful side effects that have slipped through the FDA safety net. Now, if each of those eleven recalled drugs is prescribed to just half the number of people as Merck’s Vioxx, that’s over 400 million people, or more than the population of the entire United States, consuming a potentially harmful drug. Evidently, even a three percent failure rate is too high.

Unfortunately, the economy is not as strong as it once was. Financial strains have made it nearly impossible for the government to fund FDA research without outside help. And so the FDA needs to check pharmaceutical industry pressure with one of the few tools it has left at its disposal: The postmarket safety system. The postmarket safety system is the series of reevaluations a drug faces after reaching market. Effectively, it is the FDA’s ability to recall or relabel a drug that has already been approved. In the most recent resigning of PDUFA, the act included a clause mandating the allocation of PDUFA fees to post-market safety. This is the first time the act included such a clause, and the results have been excellent. The smoking cessation drugs Chantix and Zyban, for instance, were recently relabeled to warn users against potentially harmful mood altering side effects.[9] Similarly, the FDA advisory committee recently urged for prescription painkillers such as Vicodin and Percocet, which combine opiates with acetaminophen, to be banned.[10] These postmarket alterations show not only that drugs with harmful side effects do slip through the FDA’s safety net, but also that a strong postmarket safety system is necessary and effective.

With PDUFA IV, the most recently signed version of PDUFA, an allocation of approximately $29.3 million was set aside for the enhancement of the postmarket safety system.[11] The positive effects of this allocation are clear. With the act setting a base target revenue of $392.8 million, however, the small fraction allotted to postmarket regulations is not enough. To ensure that pharmaceutical industry pressure doesn’t flood the market with unsafe drugs, a larger allocation of funds should go towards monitoring drug recall and relabeling.

Written by Nick Bakshi

[1]Advisory Committee on the Food and Drug Administration, Final Report, May 1991.

[2] Committee on the Assessment of the US Drug Safety System, Institute of Medicine, The Future of Drug Safety: Promoting and Protecting the Health of the Public. Washington, DC: National Academy of Sciences, 2007.

[3] Wood , Susan . “Reauthorizing the Prescription Drug User Fee Act: How are PDUFA, the FDA Budget, and Drug Safety Related?.” Rapid Public Health Policy Response Project (2007): Print.

[4] Wood , Susan . “Reauthorizing the Prescription Drug User Fee Act: How are PDUFA, the FDA Budget, and Drug Safety Related?.” Rapid Public Health Policy Response Project (2007): Print.

[5] Wood , Susan . “Reauthorizing the Prescription Drug User Fee Act: How are PDUFA, the FDA Budget, and Drug Safety Related?.” Rapid Public Health Policy Response Project (2007): Print.

[6] Knox, Richard. “Merck Pulls Arthritis Drug Vioxx from Market.” NPR Web.6 Jul 2009. <>.

[7] Press release, “PhRMA Statement on the IOM Drug Safety Report.” Sept. 22, 2006.

[8] Owens, Joanna. “2006 Drug Approvals: Finding the Niche.” Nature Reviews Web.6 Jul 2009. <>.

[9] “Public Health Advisory: FDA Requires New Boxed Warnings for the Smoking Cessation Drugs Chantix and Zyban.” U.S. Food and Drug Administration 07 Jan 2009 Web.6 Jul 2009. <>.

[10] “FDA Panel Urges Ban on Vicodin, Percocet.” AJC 30 June 2009 Web.6 Jul 2009. <>.

[11] Wood , Susan . “Reauthorizing the Prescription Drug User Fee Act: How are PDUFA, the FDA Budget, and Drug Safety Related?.” Rapid Public Health Policy Response Project (2007): Print.

Ted Oshman


Ted Oshman has been with The Oshman Firm since 1988 serving clients for over 25 years. Learn more about Ted's background and featured practice areas here.

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