After months of speculation, in September the White House finally nominated its lead health policy advisor, Mark McClellan, as the next FDA commissioner. McClellan is a physician and economist and, most recently, a member of the White House Council of Economic Advisors. As an MD with no direct ties to the pharmaceutical industry, he fits the basic criteria set for confirmation by the Democratic-controlled Senate.

Talk of McClellan's appointment to head FDA had circulated around Washington for several months, but he was too involved in negotiations over Medicare policy and prescription drug coverage to change hats earlier. With support from Senator Edward Kennedy (D, MA), chairman of the Senate Health, Education, Labor and Pensions Committee, McClellan enjoyed a brief and friendly confirmation hearing last month. Full senate approval was delayed by political wrangling over health coverage policy, but in the end, McClellan was confirmed before they adjourned.

The new commissioner differs from his predecessors in that he has little direct experience with FDA regulation and policy, having been more involved with health payment and cost-effectiveness issues. McClellan has an MD from Harvard and a PhD in economics from MIT. He previously held a post in the Clinton administration and is not considered a political ideologue. In fact, he garners praise on all sides for being open-minded and conscientious.

Changes AfootMcClellan will have to tackle a number of difficult administrative and policy initiatives, as well as manage a growing agency. In the absence of a permanent leader, those tasks have been handled by FDA deputy commissioner Lester Crawford, who has demonstrated strong leadership skills and a willingness to address thorny issues. McClellan will do well to encourage Crawford to continue as his right-hand aide, a role that would compensate for the new commissioner's own lack of administrative experience.

Strong agency management will be particularly important in this time of significant FDA expansion resulting from a boost in resources and personnel to support anti-bioterrorism activities. The agency has experienced its biggest growth in the last 30 years, in what Crawford termed in a September speech as "the most important legislative year in FDA's history." Bioterrorism legislation has provided the agency with 800 additional employees, most of them earmarked for FDA's field force to monitor imports that could threaten the nation's food supply and harm public health. FDA also gained authority to hire another 450 staffers under the Prescription Drug User Fee Act (PDUFA), which Congress reauthorized in June. Much of the money added by PDUFA will help increase FDA surveillance of new drugs and biologics during their first years on the market.

One important undertaking is FDA's re-examination of its legal authority to regulate commercial speech related to pharmaceuticals and other products. The agency published a request for comment on that topic last May as part of a broad review of its policies regarding prescription drug advertising, product labeling, pharmaceutical marketing to physicians, and additional communications issues affecting public health. FDA staffers are examining the first round of public comments and hope to issue a preliminary proposal next year.

In August, Crawford launched a major agency re-examination of good manufacturing practices (GMPs). That is part of a broader shift to risk-based regulation at the agency, an approach that aims to focus FDA's limited resources more on high-risk products and activities. Agency officials are developing a "road map" for overhauling manufacturing standards for human and animal drugs and biologics and plan to extend the initiative to foods following the publication of long-awaited GMPs for dietary supplements.

FDA hopes to use the GMP review as an opportunity to promote international harmonization of manufacturing standards. Crawford met with European Union regulatory authorities in August to encourage development of more uniform manufacturing policies in the United States, Europe, and Japan. The issue now may be added to the agenda of the International Conference on Harmonization (ICH), which has its next conference in November 2003 in Japan.

Biotech ConcernsProbably the most controversial initiative on FDA's plate is the proposed transfer of oversight for biotech therapies from the Center for Biologics Evaluation and Research (CBER) to the Center for Drug Evaluation and Research (CDER). (See PE Washington Report, October 2002.) The plan announced in September calls for CBER to retain authority over vaccines, blood, and blood products, and a new office to oversee gene therapies, somatic cell products, and tissues. Monoclonal antibodies and proteins will move to CDER next year.

In response to emerging criticism, FDA officials say the proposed shift is preferable to combining CDER and CBER. They also stress that CBER will continue to play a vital role in encouraging development of new therapies and vaccines to protect the public against bioterrorist threats.

Although manufacturers publicly support the change, some say privately that their complaints about CBER's slow application reviews and confusion about product development requirements aimed only to spur changes in management and systems, but they never envisioned such a wholesale shift in oversight. CBER leaders have issued reports demonstrating that their application approval times compare favorably with those for new molecular entities and that no CBER therapies have been recalled for safety reasons. (See "Not So Slow.") They claim that the pending shift of biotech therapy oversight to CDER could disrupt the regulatory framework for biologics, possibly raising safety and efficacy concerns about emerging technologies.

Crawford acknowledged that consolidating the review of drugs and biologics "under one roof" is a "very sensitive undertaking." The first challenge of the high-level transition team headed by FDA senior associate commissioner Murray Lumpkin is to determine which biotech products should shift to CDER. Although some transfers are more obvious than others, it is not clear whether therapeutic protein vaccines or recombinant blood products should remain in CBER. Decisions about which product categories go where will affect the assignment of CBER reviewers to CDER offices.

FDA officials insist that no staff reductions will result from the consolidation, but observers predict a major "brain drain" from the agency as top scientists leave for academia, research institutes, and industry. At his confirmation hearing, McClellan identified the coming retirement of one-third of FDA's workforce as a major challenge and ensured Congress that efforts to enhance FDA's work environment are "a top priority."

The difference in standards for electronic submissions between CBER and CDER could be a problem, as could their different field inspection programs. CBER funding will be a critical topic, because that center stands to lose about three-quarters of its user fee revenues. Biotech companies planning to file new license applications in the next few months fear a slowdown in the approval process. FDA officials believe that the change will yield a more streamlined regulatory and review process that should spur biotech R&D, but other FDA officials fear that efforts to "fix" the CBER regulatory process will only break a successful model.