Although the main elements of the legislation have been known for months (see BioPharm International, September 2007), many important details were finalized only at the very end of the debate. There had been uncertainty over what activities would be part of the new Risk Evaluation and Mitigation Strategy (REMS) program, and what requirements would apply to all drugs.

The final bill enhances FDA authority to require labeling changes, additional postmarket studies, and advertising curbs for all drugs and biologics, not just for products that warrant a REMS. The legislation stops short of requiring a REMS for all new drugs, as originally proposed, and leaves it up to FDA to decide whether a drug seeking market approval warrants REMS components to ensure that the product's benefits outweigh the risks. FDAAA also authorizes FDA to require agency pre-review of planned television ads, and it expands current clinical trial registration requirements to include all trials for drugs, biologics, and medical devices beyond Phase 1 intended to support market applications. This trial registration system will link to a clinical trial results database that will eventually give the public access to information on the outcomes and safety issues generated by these trials.

Although the legislation authorizes Congress to provide additional funds to accomplish the many goals established by this complex bill, FDA is unlikely to get all the money it needs. And there may be little in added resources for FDA initiatives to improve the drug development process or to spur development of new antibiotics. The Reagan-Udall Foundation established by FDAAA is meant to award grants to scientists in and outside the agency engaged in projects related to FDA's Critical Path initiative, but the agency is authorized to spend a maximum of $1.3 million on the program, and that funding has to come from its own tight budget.

Many observers believe that FDA's enhanced authority to require companies to conduct postapproval studies, make labeling changes, and clearly disclose risks in direct-to-consumer ads will limit the agency's use of REMS. Manufacturers that fail to make requested labeling changes, conduct timely postmarketing studies, or implement an approved REMS, would be in violation of the law and subject to civil monetary penalties. This new enforcement policy plus the added regulatory tools will make the agency less likely to delay a new approval, observes Scott Lassman of WilmerHale.

Most biotech therapies are likely to be identified as "high risk" and thus candidates for REMS. The prospect of stiffer label warnings, limited distribution programs, and broad research disclosure may "make marginal drugs even more risky" for R&D programs, observes John Kamp, executive director of the Coalition for Healthcare Communication. Safety or efficacy questions about a product in Phase 2, he predicts, may make a company hesitant about going forward.

Jill Wechsler is BioPharm International's Washington editor, 7715 Rocton Avenue, Chevy Chase, MD 20815, 301.656.4634, jwechsler@advanstar.com