Harvey Fineberg
But to do that, the FDA needs increased authority and resources, a better scientific review system, greater flexibility in devising regulatory responses to fit each situation, and an agency head who is insulated from political whims, he said.
At the 146th Cutter Lecture on Preventive Medicine, Fineberg answered the question posed in his title - "An FDA for the 21st Century: Are Safety and Speed Compatible?" - by discussing a recently published analysis of the U.S. drug safety system.
The report, "The Future of Drug Safety: Promoting and Protecting the Health of the Public," was released by the IOM in September. The IOM, a branch of the private National Academy of Sciences, was established by congressional charter to advise the government. The IOM studied the issue at the request of the FDA and the Department of Health and Human Services.
The FDA was created 101 years ago in response to public outrage about the Chicago meatpacking industry portrayed in Upton Sinclair's 1906 novel, "The Jungle," explained Fineberg, a former HSPH dean and Harvard provost. Since then, a successive array of problems revealed through exposé public health tragedies have led to increased authority and greater protection against inappropriate approval of new drugs.
By the 1970s, increased scrutiny of new drug submissions led to widespread complaints of a drug lag. "The perceived problem with the FDA changed from not protecting the public against bad things to preventing good things from getting out there in a timely fashion," he said.
Deregulation in the 1980s slashed the FDA budget and reduced staff. In 1992, the new Prescription Drug User Fee Act authorized direct drug company payments to the FDA to speed up review of new drug applications. It worked. By the end of the decade, the median review for new drugs dropped from 19 to 12 months, and from 15 months to less than six months for priority drugs. The User Fee Act has been renewed every five years and comes up for reauthorization later this year at a time of increased public concern about drug safety.
The latest crisis of confidence - the 2005 Merck recall and withdrawal of rofecoxib (Vioxx(r)) for increased risk of heart attacks and strokes - highlighted the problem of safety after a drug is approved.
"There is a history of lurching back and forth between the goals of [keeping] medicine safe and getting out the medicine needed by the public," Fineberg said. "Now, once you get approval, it's all or nothing, black or white." There is only a passive reporting system to detect rare safety problems that may emerge with more widespread use of the drug. The challenge for the future is to prevent ill effects of medications, vaccines, and other health interventions while allowing effective new drugs to reach patients, he said.
The IOM report concentrated on beefing up the postapproval phase of drug development. First, the FDA's Center for Drug Evaluation and Research (CDER) needs the authority and public money to carry out the safety mandate for drugs newly released on the market, he said. If the User Fee Act is re-authorized, it should eliminate all restrictions on using the money for postmarketing studies. Congress should appropriate sufficient funding to provide adequate resources to protect public safety and remove CDER reliance on user-fee funding, which now makes up 40 percent of its budget.
New risk assessment rules and risk management programs may include conditional distribution, such as warnings in promotional material, changes in drug labels, a ban on direct-to-consumer advertising ("an abomination," Fineberg asserted), restrictions to certain facilities or pharmacies or physicians with special training or expertise, and specified additional trials or studies.
The report also recommended a six-year term to stabilize the leadership of the FDA, which has averaged terms of just two years. That leader should be scientifically and professionally qualified.
The question-and-answer period following the lecture mostly defined areas of concern outside the scope of the FDA's authority and the focus of the IOM report - such as the lack of a drug approval process to fight malaria and similarly neglected diseases in various countries, poor oversight of custom-compounded drugs for hormone replacement therapy and other uses, and off-label uses of approved drugs for unproven purposes.
U.S. Senators Edward Kennedy (D-MA) and Michael Enzi (R-WY) have introduced a bill intended to improve the FDA's ability to monitor drug safety after pharmaceuticals have been put on the market. The bill is under debate.
—CM
Copyright, 2007, President and Fellows of Harvard College
