Regulatory Beat: Crawford Faces Policy and Program Challenges

The Senate confirmed Lester Crawford in July as the official head of the Food and Drug Administration (FDA). Crawford's nomination had been put on hold as various legislators pressured FDA to approve an over-the-counter version of the "morning-after" pill, Plan B, and to support broader drug importing. Senate Finance Committee chairman Charles Grassley (R-IA) reflected broader concerns about FDA in criticizing Crawford for not tackling drug safety failures and FDA's "structural, personnel, cultural, and scientific problems." In the end, Grassley and most members of the Senate agreed that FDA would be better off with a permanent chief than without but failed to give the new commissioner unanimous approval. Crawford faces a rough road ahead as Congress and consumers continue to closely scrutinize FDA activities and initiatives.

Jill Wechsler

The situation makes it critical for Crawford to demonstrate that FDA decisions will be based on scientific and medical evidence — and not on pressure from industry or political leaders. With five years experience as acting or deputy FDA commissioner, Crawford moved quickly following Senate confirmation to brief members of Congress on reports of deaths related to Mifeprex (mifepristone), announce new FDA leadership [see Stability at the Top], and answer pointed questions from members of the House Appropriations subcommittee, who are responsible for approving FDA's budget.

At that hearing in July, Rep. Rosa DeLauro (D-CT) reflected the fairly negative opinion of FDA operations, citing flu vaccine shortages due to "inept oversight," delayed withdrawals of drugs such as Vioxx, and failure to enforce an animal feed ban to protect against mad cow disease. In his written testimony, Crawford outlined key challenges facing FDA in the coming year. The agency has fast-growing responsibilities for ensuring the safety of the nation's food supply, as well as difficulties regulating a growing number of complex medical devices. He also noted FDA's central role in protecting against bioterrorism by spurring development and ensuring production of new vaccines and countermeasures. And finally, the agency's move to its new White Oak campus in the Maryland suburbs promises to be a costly and disruptive process.

These tasks will be difficult to address in the face of a real budget squeeze on FDA. The situation prompts Crawford to talk more about "risk- based management practices," which means targeting inspections and oversight to higher-risk products and activities, an approach that applies particularly to drug and biotech manufacturing. Crawford acknowledges that in the current "environment of fiscal restraint," FDA field investigators should spend more time and resources inspecting "highly complex or high-risk drug products and processes." The unstated promise is that FDA will reduce inspections and oversight for manufacturers that adopt new technologies capable of assuring quality drug production.

ENSURING DRUG SAFETY

The biggest challenge for the new commissioner is to demonstrate that FDA can identify and prevent drug safety problems. Members of Congress have proposed legislation to give FDA authority to require label changes and to complete Phase 4 studies. The legislators also want to expand the agency's Office of Drug Safety and make it more independent of drug approval activities in the Center for Drug Evaluation and Research (CDER) (see Regulatory Beat, August 2005). FDA officials look to a panel convened by the Institute of Medicine (IOM) to provide a roadmap by next July (2006) for revising its monitoring system for drug-adverse events without adding new layers to FDA regulatory operations. At the House Appropriations hearing, Crawford said he was "open to discussion" of such proposals, but has refused to back any specific legislation.

Stability at the Top

Moves to expand FDA authority or restructure agency operations will gain a broader hearing in coming months as Congress prepares to tackle reauthorization of the Prescription Drug User Fee Act, which expires in 2007. FDA, biotech companies, and special interest groups are gearing up for the debate, which will require Crawford and his staff to articulate agency positions on a host of hot issues:

• Generic biologics. With patents expiring for some $10 billion worth of branded biotech therapies over the next three years, FDA is under pressure to describe a legal and regulatory pathway to permit consumer access to lower-cost, follow-on biopharmaceuticals. Crawford now believes that improved understanding of complex molecules may make it possible to characterize follow-on products. The agency has been examining scientific and technical issues related to developing and testing generic versions of approved proteins, and Crawford stated the agency would issue a report describing such approaches this fall. The challenge for FDA is to retain incentives for developing new biotech therapies while allowing public access to lower-cost, follow-on treatments that meet quality and equivalence standards. In the end, Congress may step in to provide FDA with clear legal authority to approve generic versions of biologics.

• Vaccine and drug shortages. Policy makers and health authorities are watching flu vaccine supplies carefully for the coming flu season. At the July appropriations hearing, questions about flu vaccine manufacturing prompted Jesse Goodman, director of the Center for Biologics Evaluation and Research (CBER), to report that FDA had completed inspections at Chiron's Liverpool plant and that "substantial progress has been made." But Chiron continues to experience vaccine manufacturing problems, and growing concerns about inadequate US preparedness for a possible avian flu pandemic will require FDA's continued attention to this issue.

• Drug importing. FDA has blocked individuals and third parties from bringing in drugs and biologics from other countries, claiming it lacks the authority and resources to ensure the safety and quality of such products. This stance has infuriated members of Congress who consider broader importing a good way for American consumers to access lower-cost prescription drugs. Legislators will continue to press for drug importing measures.

• Drug marketing. Crawford has expressed concerns about the increasing volume of direct-to-consumer advertising, a position echoed by members of Congress and health professionals. Pharma manufacturers have developed guidelines recommending curbs on promotion of newly approved drugs and on intimate ads in prime viewing time. Critics contend that voluntary curbs won't solve these problems, and Congress is likely to step in if the industry guidelines fail to address public complaints.

CAUSE FOR CELEBRATION

Next year (2006) will mark FDA's 100th anniversary, and Crawford already is eyeing opportunities to celebrate the agency's achievements in ensuring public access to safe foods and innovative medical products. This celebration will coincide with FDA's relocation to White Oak, a move Crawford regards as heralding a new chapter in FDA's history. For the first time in decades, the agency's multiple operations will be housed in close proximity to each other, making it easier to interact and collaborate. For patients and policy makers to share this enthusiasm, the new commissioner will have to convince them that FDA is up to the task of keeping truly dangerous medical products out of patients' hands while supporting continued biomedical innovation.

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