PhRMA DEFAULT MECHANISM FOR EMEA/U.K. APPROVED DRUGS FOLDED INTO "ACCELERATED APPROVAL" PROCESS IN FDA REFORM PROPOSAL DRAFTED BY SENATE LABOR COMMITTEE

NDAs for drugs to treat serious or life-threatening conditions that already have been approved by the European Medicines Evaluation Agency or the U.K. Medicines Control Agency would be eligible for a "fast track process" for FDA review under Senate Labor & Human Resources Committee Chairman Kassebaum's (R-Kan.) FDA reform concept paper being circulated the week of Aug. 7.

Sponsors of any drug, biologic or device intended to treat a "serious or life-threatening illness or seriously debilitating condition may submit" a "request for expedited evaluation of the product," the concept paper states. "If the FDA finds that the risk from the product is not greater than the risk from the disease or condition and there is a reasonable likelihood that the product will be effective in a significant number of patients, the FDA will grant an expedited review."

Approval of a product by the EMEA or the U.K. MCA "would be deemed evidence that the risk from the product is not greater than the risk from the condition," according to the concept paper.

"If FDA agreed to expedited review," the committee document stipulates, the agency would have "no more than 180 days to either approve the product or disapprove the product and show cause why the risk from the product would be greater than the risk from the disease or condition and why the product would not be effective in a significant number of patients."

The Labor Committee proposal represents a modification of the default approval mechanism being advocated by the Pharmaceutical Research & Manufacturers of America for drugs already approved overseas. By folding the concept into a codification of the FDA accelerated approval process, the Kassebaum proposal may substantially reduce its appeal to industry.

PhRMA is proposing that sponsors of any drug already approved by EMEA, the U.K. or any other third party designated by FDA as acceptable have an option to pursue a default approval. The burden of proof would be shifted under the PhRMA proposal, with FDA obligated to approve those applications unless it makes a definitive finding that the drug is not safe or effective. Nonapproval decisions would be published under the industry plan. The PhRMA language is retained in the joint FDA reform bill crafted by PhRMA and the Biotechnology Industry Organization ("The Pink Sheet" Aug. 7, p. 4).

While the Kassebaum proposal is limited to drugs for serious or life-threatening diseases, the PhRMA proposal likely would be more appealing for non-breakthrough drugs than for breakthroughs.

The FDA timeline currently does not pose a major threat to approval of breakthrough drugs, and the default mechanism would risk devaluing the FDA licensure if the agency approval decision were perceived as a rubber stamp or lukewarm endorsement of a third-party review. Firms also would be unlikely to risk the potentially irreversible commercial impact of a public FDA rejection for a drug. For less significant new drugs or indications, however, the PhRMA proposal could provide an appealing option to speed a decision on an application that may otherwise languish at FDA.

FDA's existing accelerated approval mechanism has not been universally popular with industry. Sponsors of AIDS drugs in particular have felt pressure to bring products to market before they have completed the process of identifying a satisfactory commercial niche. Outside the AIDS area, some companies have avoided using the accelerated process. Genentech's decision not to seek accelerated approval for Pulmozyme for cystic fibrosis allowed the company to complete cost-effectiveness analyses prior to launch to smooth the introduction of the high-priced agent.

By focusing the provision solely on breakthrough drugs, at least in the early stages of drafting, the Kassebaum proposal presents a consumer-friendly appearance. The concept paper emphasizes the issues of patient access to therapies. The potential for the goal of consumer access to conflict to some degree with sponsors' desire to control their applications is also seen in the Kassebaum proposal for medical society sponsorship of supplemental approval applications.

Under the Senate proposal, sponsors would have the option to petition for expedited review of a breakthrough drug. FDA would be required within 30 days "either to agree in writing to expedited review or provide in writing to the sponsor its reasons for not agreeing to expedited review." An agency decision not to agree to expedited review would be subject to appeal.

As with the current accelerated approval process, "FDA could approve the product for use only by specified physicians (i.e., kidney specialists) in specified settings (i.e., research institutions) and only if the sponsor agreed in writing to conduct additional studies that may be requested" by the agency, according to the paper.

The Kassebaum proposal also would grant FDA the "authority to contract out the evaluation of parts or all of applications, to use external review organizations, and to hire as temporary government employees expert individuals to improve the agency's efficiency and the scientific quality of its evaluations." However, the Senate committee notes, FDA "would retain the final responsibility for the approval or disapproval of an application."