Jill Wechsler

Curbs on drug advertising, stiffer label warnings, limited distribution programs, and broad research disclosure may all combine to limit prescribing. This "makes marginal drugs even more risky" for industry R&D programs, observes attorney John Kamp. Safety or efficacy questions about a product in Phase II, he predicts, will make a company hesitant about going forward.

Conversely, all the new regulatory tools now available to FDA could boost the agency's confidence about being able to tackle safety issues that crop up after a drug comes to market. Such enhanced authority could make the agency more willing to bring a drug to market and evaluate the need for added safeguards later.

Wins and Losses

Overall, manufacturers applauded the enactment of FDAAA. The bill retained incentives for industry to conduct additional pediatric studies, curbed the scope of new penalties for fraud and noncompliance, and kept the door open for DTC advertising of new drugs. At the same time, FDA gained more authority to control drug marketing and labeling, require postapproval studies, establish active surveillance systems, and make clinical trials more transparent.

Implementation will be an arduous task. The legislation contains at least 200 specific provisions, noted FDA Commissioner Andrew von Eschenbach. The job of sorting through all the new requirements now falls to FDA Deputy Commissioner Janet Woodcock. She recently took over as acting director of the Center for Drug Evaluation and Research (CDER) following the departure of Steven Galson to be Department of Health and Human Services acting surgeon general. Woodcock implemented the user fee program as CDER director for 10 years and knows the ropes. But she may not get enough new resources to do the job smoothly—or to modernize drug development. The new Reagan-Udall Foundation established by FDAAA to support FDA's Critical Path Initiative is authorized to receive a maximum $1.3 million, and that funding has to come from FDA's own tight budget.

Some last-minute changes also may create serious legal problems for pharma. The final bill contains very murky language on whether FDA regulations preempt state drug-labeling laws. This thorny issue has pitted federal regulators against states eager to establish more-stringent disclosure policies for medical products. The vagueness of the FDAAA provision is expected to lead to a major legal battle, which may very well end up before the Supreme Court.

Enhancing Safety

There was uncertainty over what requirements would fall under the new Risk Evaluation and Mitigation Strategy (REMS) program and what new mandates would apply more broadly. In the end, FDAAA authorizes FDA to impose labeling changes, additional postmarket studies, and advertising curbs on all drugs—not just for those products that warrant a REMS. Conversely, the legislation stops short of requiring a REMS for all new drugs, as originally proposed, and leaves it to FDA to decide whether a new product warrants added safeguards to minimize risks.

FDAAA also expands current clinical trial registration requirements to cover all trials for drugs, biologics, and medical devices beyond Phase I intended to support market applications. This trial registration system will link to an extensive clinical trial results database that eventually will make available to the public information on the outcomes and safety issues generated by the studies.