New Era at FDA

After months of delay, the Senate confirmed Lester Crawford in July as the official head of the Food and Drug Administration. Crawford's nomination had been put on hold as various legislators sought to pressure FDA to take action on pet issues, such as drug importing and approval of an over-the-counter version of the "morning-after" pill Plan B. Senate Finance Committee chairman Charles Grassley (R-Iowa) reflected general concerns about the agency in criticizing Crawford for not tackling drug safety failures and FDA's "structural, personnel, cultural and scientific problems."

Jill Wechsler

In the end, Grassley and most Senators agreed with the leadership on both sides of the aisle that FDA would be better off with a permanent chief than without. Now it's up to the new commissioner to demonstrate that FDA decisions will be based on scientific and medical evidence —and not on pressure from industry or political leaders.

After five years as FDA acting or deputy commissioner, Crawford was able to hit the ground running following Senate confirmation to the top job. He briefed members of Congress on reports of deaths related to Mifeprex (mifepristone), announced new FDA leadership [see sidebar on Stability at the Top], and answered pointed questions from members of the House Appropriations subcommittee that approves FDA's budget.

Stability at the Top

At that hearing, Rep. Rosa DeLauro (D-Conn) launched a broad critique of Crawford and FDA, 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. All signs point to a rough road ahead as Congress and consumers continue to closely scrutinize FDA initiatives.

In his written testimony, Crawford outlined key administrative challenges facing FDA in the coming year. There is expanded responsibility for ensuring the safety of the nation's food supply and pressure to implement a new user fee program for medical devices to help bring increasingly complex medical products to market. FDA is in the center of federal efforts to protect against bioterrorism by spurring development of new vaccines and countermeasures. And much of the agency is moving to a new White Oak campus in the Maryland suburbs, a costly and disruptive process. In anticipation of this move, the Center for Drug Evaluation and Research's (CDER's) Office of New Drugs (OND) has reassigned a number of product review divisions, some the result of creating an Office of Nonprescription Products, which handles applications for switches as well as for new over-the-counter drugs.

OND also has created a new Office of Oncology Drug Products, which includes drugs, biologics and imaging products to treat cancer. With the move to White Oak, other biotech therapies will be reassigned to relevant new drug review divisions according to indication.

Ensuring drug safety

Probably the most important issue on Crawford's agenda is to show that FDA can identify and prevent drug safety problems. Members of Congress have proposed legislation giving FDA more authority to require label changes and to complete Phase IV studies. The legislators also want to expand the agency's Office of Drug Safety (ODS) and make it more independent of drug approval activities in CDER.

FDA is looking to a panel convened by the Institute of Medicine (IOM) to provide a roadmap by next July (2006) for revising its system for monitoring drug adverse events without expanding FDA operations. At the July meeting of the IOM panel, CDER officials described the current system for capturing and assessing information on drug risks and benefits during clinical trials and after a drug comes to market, emphasizing the importance of interaction between staffers in ODS and OND. Paul Seligman, director of CDER's Office of Pharmacoepidemiology and Statistical Science (OPPS), also acknowledged that additional resources could help FDA gain more valuable information on drug utilization and safety from real-world resources.

Crawford was reluctant to openly ask Congress for more money or expanded authority, saying only that he is "open to discuss" various proposals. He noted at the appropriations hearing that FDA is reviewing industry's record for completing Phase IV studies, which may alter his future views. He also pointed to FDA's Drug Safety Oversight Board and "Drug Watch" safety information Web site as more appropriate ways to provide the public with more drug risk information.

Following the critical path

While addressing charges of inept handling of safety issues, Crawford needs to counter fears in the research community that FDA may try to avoid approving any risky new drugs by requiring sponsors to conduct longer and larger clinical studies. At the July IOM meeting, OND Director John Jenkins acknowledged the "unintended consequences" of slower drug development and approval: demanding larger trials could prompt sponsors to cancel drug development programs altogether, and longer studies could delay patient access to potentially valuable treatments. But members of Congress on both sides of the aisle reject concerns about higher drug development costs—especially, as Rep. Jo Ann Emerson (R-Mo) commented, with pharma companies enjoying huge profits.

Meanwhile, continued focus on drug safety has put FDA's "Critical Path" initiative on the back burner. After issuing a report more than a year ago outlining the critical path to biomedical product development, FDA still has not published a promised list of critical path opportunities for collaborative research to spur drug innovation. Crawford regularly mentions the importance of pursuing critical path initiatives and now is in a position to show that he will do so.

Changes ahead

Moves to expand FDA oversight 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 (PDFUA), which expires in 2007. FDA, pharma companies and 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:

• Drug importing. FDA has blocked individuals and third parties from bringing in drugs from other countries, claiming that the agency lacks 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 and continue to press for legislative action.

• 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 biopharmaceuticals. Innovator firms want FDA to require generics makers to conduct additional clinical trials, while generics firms claim they can document product equivalence through modified development programs. Crawford said the agency will issue a report this fall recommending R&D approaches for follow-on biologics, but Congress probably will have to step in to clarify FDA legal authority in this area.

• Drug marketing. Crawford has expressed concerns about the increasing volume of direct-to-consumer drug advertising, sentiments echoed by members of Congress and health professionals. Pharma companies have developed guidelines to curb more objectionable advertising practices, but critics contend that a voluntary approach is not enough. If the guidelines fail to address public complaints in the coming year, Congress is likely to propose a remedy.

• Revising physician labeling. FDA has been working several years on new regulations to streamline and clarify information in professional drug labels. Manufacturers have objected that some labeling changes raise liability concerns, but Crawford has promised a final rule this fall.

Next year (2006) will mark the 100th anniversary of the Food and Drug Administration, and Crawford already is eyeing opportunities to mark the agency's achievements in ensuring public access to safe foods and innovative medical products. The celebration will coincide with FDA's relocation to White Oak, a move that Crawford believes heralds a new chapter in FDA's history. For the first time in decades, the agency's multiple operations will be housed in close proximity, making it easier to interact and collaborate. In order for patients and policy makers to share this enthusiasm, the new commissioner will have to convince his critics that FDA is up to the task of keeping dangerous medical products out of patients' hands while enabling public access to valuable biomedical therapies.

Jill Wechsler is the Washington editor of Applied Clinical Trials, (301) 656-4634 jwechsler@advanstar.com