FDA Drug Approval Process under Scrutiny

FDAThe U.S. Food and Drug Administration (FDA) is facing renewed criticism over the process by which it approves drugs for market. Recent reports indicate many drugs are approved before they are proven safe, and problems with the agency's structure and processes prevent it from fulfilling its mission. Subsequently, Congress has started using its oversight powers to scrutinize the agency, and the clamor for FDA reform is growing louder.

The Federal Food Drug and Cosmetic Act requires FDA to ensure the safety of new drugs before the agency approves the drugs for market. However, operating within a provision of the law, FDA often approves drugs before safety is established. The agency then requires drug manufacturers to further study drugs while they are on the market. These "post-marketing commitments" serve to streamline the drug approval process.

FDA recently revealed that many of the post-marketing commitments go unfulfilled. On Feb. 2, the agency published a report in the Federal Register detailing the progress of post-marketing commitments, which in Fiscal Year 2006 numbered 1,259. As The NewStandard reported, FDA said drug companies "had yet to initiate 71 percent of outstanding 'post-market' safety evaluations." Meanwhile, only 11 percent have been submitted. These drugs remain on the market, yet neither FDA nor drug makers have proved their safety.

Congress also recently expressed concern over the FDA drug approval process. On Feb. 13, the House Committee on Energy and Commerce's Subcommittee on Oversight and Investigation held a hearing titled "The Adequacy of FDA Efforts to Assure the Safety of the Drug Supply." The hearing occurred in response to recent regulatory failures that allowed dangerous drugs on the market, such as the highly publicized Vioxx incident.

Hearing witnesses testified that the FDA drug approval process is subject to industry influence and that agency managers sacrifice sound science in the name of expeditious approval. Ann Marie Cisneros, a clinical researcher, accused the pharmaceutical company Aventis of being complicit in a fraudulent clinical research project which Aventis had sponsored.

The testimony of Dr. David B. Ross, a physician and former FDA pharmaceutical reviewer, told the story of the antibiotic Ketek. Dr. Ross claimed Ketek was approved despite persistent warnings of its danger: "FDA managers were so bent on approving Ketek that they suppressed evidence of fraud and pressured reviewers — including myself — to change their reviews."

The criticism leveled at FDA is not new. The Government Accountability Office (GAO), the investigative arm of Congress, issued a report in March 2006 identifying significant gaps in FDA's ability to monitor and regulate post-market drugs. The GAO report mentioned organizational structure, insufficient oversight and poor data availability as some of the major problems facing FDA. GAO recommended Congress expand FDA's regulatory authority for post-market drugs.

In September 2006, the National Academy of Sciences Institute of Medicine also identified problems at FDA. Most notably, "FDA and the pharmaceutical industry do not consistently demonstrate accountability and transparency to the public by communicating safety concerns in a timely and effective fashion."

The mounting evidence in the case for FDA reform increases the likelihood of congressional action. Congress will likely take up the renewal of the Prescription Drug User Fee Act (PDUFA), which is set to expire this year. The legislation gives FDA the authority to require drug manufacturers to pay fees that the agency then uses to conduct drug reviews. In his proposed FY 08 budget released in early February, President George W. Bush called for new industry fees to further finance FDA. User fees from regulated companies would account for 21.3 percent of FDA's budget and pay for nearly 60 percent of reviews, according to USA Today.

FDA critics are skeptical of the industry-paid user fees. In the House hearing, Dr. Steven E. Nissen, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic Foundation, chastised PDUFA: "We started down the wrong pathway when we said that the regulated industry was going to pay the FDA to regulate itself."

In addition to PDUFA reauthorization, two Senate bills aim to enact reforms within FDA. A bill introduced by Sens. Charles Grassley (R-IA) and Christopher Dodd (D-CT) would separate FDA's drug safety office from its drug approval office, thus elevating FDA reviewers to the same status as managers who approve drugs, according to Congressional Quarterly (subscription). In an attempt to improve post-market regulation, a bill introduced by Sens. Edward Kennedy (D-MA) and Michael Enzi (R-WY) would focus more on the drug safety processes as they are currently used. Both bills are currently in committee.

It is unclear whether the drug approval process at FDA will be subject to reform. However, with the safety of many post-market drugs unknown, the issue is unlikely to go away. In his testimony, Ross chided his former employer: "Overall, there is a culture of approval [at FDA.]" He indicated that approval, not safety, is the top priority, adding, "If you can get a product on the market…then you find some way of doing it."

© 2006 OMB Watch