Illustration: Roger Schillerstrom
Scientists at the US Food and Drug Administration (FDA) are continuing to exit the agency, creating a “brain drain” that many say is contributing to lackluster performance. Some 30 percent of the FDA’s regular 10,100-person workforce is eligible to retire, and many are—or are taking more lucrative jobs in industry.
Among the possible results: FDA is taking longer than the 180 days allowed under Federal law to process generic drug applications. And new drugs that had been approved shortly before the end of their deadlines show evidence of more safety problems down the road than did other drugs, indicating more pressure on and poorer work by FDA drug reviewers.
“What you have now is a big sucking sound of these staffers leaving FDA and going into the more lucrative side of the business or packing it in and retiring entirely,” Steve Brozak, an analyst with WBB Securities, San Diego, Calif., told USA Today. “This cannot have any positive effect whatsoever.”
The exodus could not come at a worse time: Congress and the Administration have added hundreds of new responsibilities to the FDA, even as the number of government-funded employees has fallen from about 9,000 to 8,000. Passage of the FDA Amendments Act of 2007 (FDAAA) alone gave the agency more than 200 new and largely unfunded responsibilities for drug safety oversight.
In April, the FDA began a nationwide recruitment effort to quickly fill more than 1,300 new and vacant positions for biologists, chemists, medical officers, mathematical statisticians, and investigators. “Each month that there is a delay in bringing critical staff on board impairs the agency’s ability to fulfill [its] mission,” said John Dyer, FDA’s deputy commissioner for operations and chief operating officer. The agency has been granted special authority to bypass the government’s usual hiring bureaucracy.
FDA is hoping by the end of September to fill more than 600 new positions and to backfill more than 700 others to implement the FDAAA, the Food Protection Plan, and the Import Safety Action Plan. That’s nearly triple the number of people the agency hired from 2005 to 2007, Dyer said. The Center for Drug Evaluation and Research (CDER) is nearly halfway through its hiring goal, having added more than 300 new employees thus far.
While bulking up staff will no doubt help, more than sheer numbers will be needed to improve the agency’s performance, outside experts say. Strict deadlines for reviewing new drugs contribute to stress, and staff members who disagree with management are discouraged from speaking up, the Institute of Medicine (IOM) said in a report last year.
The IOM report, “The Future of Drug Safety: Promoting and Protecting the Health of the Public,” concluded that FDA’s drug safety system was impaired by “serious resource constraints that weaken the quality and quantity of the science that is brought to bear on drug safety [and] an organizational culture in CDER that is not optimally functional.”
The FDA’s shortage of personnel and resources is also a major factor behind the agency’s dismal performance in processing generic drug applications. According to a June report by the Health and Human Services Inspector General Daniel Levinson, the median time for FDA to review generic drug applications was 217 days, exceeding the 180-day review requirement for 46 percent of all original Abbreviated New Drug Applications. In the end, FDA rejected nearly 96 percent of applications, mostly because they failed to meet agency standards. The Inspector General suggested FDA give industry more and better guidance.
When it comes to new drugs, the IOM report found that the Prescription Drug User Fee Act (PDUFA), the mechanism that accounts for more than half of CDER’s funding through industry user fees is “excessively oriented toward supporting speed of approval and insufficiently attentive to safety.” Tighter review schedules have created “a sweatshop environment that’s causing high staff turnover,” said CDER Director Janet Woodcock, MD, in a 2000 newsletter. An FDA spokesman recently said Dr. Woodcock no longer holds that view.
Under PDUFA, the FDA has pledged to make decisions on 90 percent of new drug applications within 10 months after submission. In exchange, the agency collects user fees from industry to hire additional reviewers. These fees will account for about half of the $680 million the agency will spend on new drug reviews this year.
Sweatshop or not, according to a recent study by Harvard University government professor Daniel Carpenter, PhD, published in the New England Journal of Medicine in March and updated in July, found that between 1993 and 2005, 88 drugs approved by the FDA soon before their regulatory deadlines had a 15 percent chance of being subsequently flagged for safety problems (including black-box warnings and complete withdrawal) compared to just 5 percent for 226 other drugs.
Drugs approved at or near the deadlines and later withdrawn include Merck and Co.’s painkiller Vioxx (withdrawn in 2004 following reports of adverse cardiovascular events); Pfizer Inc.’s diabetes drug Rezulin (withdrawn from the US market in 2000 following reports of liver toxicity); and Bayer AG’s cholesterol-lowering Baycol (withdrawn from the US market in 2001 following reports of sometimes fatal rhabdomyolysis).
The FDA disputed Carpenter’s findings, questioning the accuracy of some data. Carpenter updated his findings in July but is standing by his conclusions. In a letter published in the NEJM in July, FDA economist Clark Nardinelli, PhD, wrote that black-box warnings are common among priority drugs approved during the first cycle, including drugs for HIV, AIDS “and other life-threatening conditions for which greater safety risks may be accepted and for which approvals may be based on more limited data.”
About the Author
Contributing editor Ted Agres, MBA, is a veteran science writer in Washington, DC. He writes frequently about the policy, politics, and business aspects of life sciences.
This article was published in Drug Discovery & Development magazine: Vol. 11, No. 8, August, 2008, pp. 10-12.
Filed Under: Drug Discovery