New FDA Leader Has Full Agenda

After months of stalemate between the White House and Senate democrats over the appointment of a new FDA commissioner, Health and Human Services secretary Tommy Thompson took a shortcut February 26 and named Lester Crawford deputy commissioner. The move allowed Crawford to start work at FDA immediately, skipping the lengthy Senate confirmation process.

As a food safety expert and veterinarian, Crawford was considered a top candidate for the commissioner's job last fall. He most recently headed Virginia Tech's Center for Food and Nutrition Policy and, in the 1980s, served in the Department of Agriculture and as director of FDA's Center for Veterinary Medicine. But consumer advocates object that he is too strongly tied to industry because of his previous positions at the National Food Processors Association and at an agricultural chemical firm. Moreover, Crawford is not an MD, the usual credential for an FDA commissioner.

With Crawford coming on board, Bern Schwetz is able to return to his job as the agency's senior advisor for science after being FDA's acting principal deputy commissioner for more than a year. Thompson and the White House insist that they are actively looking for a permanent FDA commissioner, but Crawford's appointment gives him an opportunity to "audition" for the job. Pharma companies have been cool to the nomination of Alastair Wood of Vanderbilt University, but his name still appears on commissioner "short lists." If Senate democrats continue to nix anyone appearing too pro-industry, the impasse could leave Crawford the de facto head of FDA for some time.

PDUFA 3 Now

Crawford's first public appearance as deputy commissioner was his testimony before the House Energy and Commerce Committee last month about the critical need to reauthorize the Prescription Drug User Fee Act (PDUFA) immediately. After extensive negotiations, FDA officials and industry leaders informed legislators that they had reached agreement on a framework for PDUFA 3. The deal calls for a significant increase in fees to expand agency oversight of marketed medications. User fees will be $223 million next year, a $90 million increase over 2001. The total will rise to $260 million in 2007. The fee hike will apply to applications, products, and facilities to distribute the burden among new and approved therapies.

The plan is to double the size of the Office of Drug Safety (ODS) in the Center for Drug Evaluation and Research (CDER) during the next five years, from about 80 to 160 staffers. That will enable the agency to boost its oversight of safety and risk issues during the "peri-approval" period between pre- and post-approval, which is defined as two years for a standard drug and three years for fast-track therapies. ODS will also be able to evaluate risk management plans that sponsors can submit with new drug applications that raise safety concerns.

Other key provisions in the PDUFA 3 agreement include

• continuation of current goals and procedures governing application reviews for new drugs and biologics, as well as investment in new FDA information technology

• a new program allowing biotech manufacturers to request that the Center for Biologics Evaluation and Research (CBER) bring in a paid outside specialist to provide expertise on clinical trial design for innovative therapies

• allocation of some user fee revenues for the FDA commissioner to examine why application approval times vary between CDER and CBER and among review divisions of each center

• support for a pilot test of a "cumulative marketing application" review concept that involves submitting NDA modules instead of delaying review until the entire application is complete.

Congress urged FDA to finalize PDUFA immediately so legislators will have a chance to reauthorize the program before summer. PDUFA 2 expires on September 30, but FDA will have to warn staffers of possible layoffs if it is not approved by August 1. In contrast to previous years, FDA has used up all its fee reserves and has no funding cushion. Continued uncertainty about the long-term fate of the program may prompt talented scientists to leave the agency for lucrative jobs in industry.

CERTs At Risk?

The Bush administration proposal to cut funding for HHS' Agency for Healthcare Research and Quality (AHRQ) casts a shadow over the future of the Centers for Education and Research on Therapeutics (CERTs), which study efforts to improve the safe and effective use of medicines. AHRQ has established seven CERTs at academic research institutions during the past two years. Now part of a $5 million program, those centers have been studying ways to

• improve dosing of anti-HIV therapies

• reduce drug interactions

• use therapeutics appropriately in pediatric and cardiovascular patient populations

• help large managed care databases provide information about prescribing patterns, dosing outcomes, and policies.

Even more threatened is AHRQ support for independent research on drug prescribing and use. The budget plan would end support for studies on various issues, including appropriate use of medicines by the elderly and how new technologies can reduce prescribing errors.

The AHRQ budget is a tiny $300 million this year, and HHS would save only $50 million with its proposed reduction. But the move would devastate AHRQ, and it appears to fly in the face of secretary Thompson's support for programs and policies to enhance healthcare safety. Congress is expected to reverse the cut, but the funding proposal reveals the vulnerability of health outcomes research programs.

Filling Vacancies

In addition to naming Crawford to temporarily head FDA, Thompson moved to fill some big holes in the HHS hierarchy last month. There was action to appoint a new head of the National Institutes of Health, as well as a director for the Health Resources and Services Administration. But the director of the Centers for Disease Control and Prevention resigned soon after the departure of HHS surgeon general David Satcher. And those vacancies raise questions about who-besides Thompson-will oversee the health policy aspects of the nation's war on terrorism. Thompson may turn to former Merck executive Eve Slater, who has been confirmed as HHS assistant secretary for health, but that traditionally has not been a high-profile job.

Thompson remains under pressure to fill the top job at FDA. Without the stature of a formally confirmed commissioner, Crawford will find it difficult to decide major policy initiatives or to make key staff appointments. Continuing disputes over HHS leadership appointments are a sign of just how visible and political the world of science and medicine has become in Washington.

Although many Democrats on the House panel talked about adding provisions to the PDUFA reauthorization bill that would accelerate FDA approval of generic therapies, Congressional leaders want to approve "clean" PDUFA legislation to avoid delay. But pressure is growing for policy changes to spur generic therapies to market, and now the business community and state governors are chiming in. Representatives from those groups formed the "Business for Affordable Medicine" (BAM) coalition in February to press Congress for Waxman-Hatch revisions that will prevent brand-name companies from extending patents beyond their original expiration dates.

One aim is to alter the current policy that allows an innovator company to block FDA approval of generics for 30 months by filing a patent infringement suit against the first generics competitor. The coalition also cites other loopholes in the law that make it easy for innovators to delay generics competition.

The Pharmaceutical Research and Manufacturers of America responded by pointing out that Waxman-Hatch has allowed generics to gain control of almost half of the US pharma market. The association warns that any changes in the current delicate balance would erode incentives for new R&D.

In pressing for policy changes, BAM is eyeing a sizeable list of important medicines about to lose patent coverage in the next three years. The coalition estimates that state Medicaid programs will save $600 million annually if patents on 17 therapies expire on schedule during 2002-2004 and generics become quickly available.

Despite the dire fiscal problems facing many state Medicaid programs, prospects are low for Congress to tackle Waxman-Hatch revisions this year. One alternative is to add provisions to Medicare reform legislation that encourages generics prescribing in any Medicare pharmacy benefit plan. That could consist of lower co-pays for generics and possibly very high co-pays for brand-name products with heavy DTC support. State governments may consider similar policies to promote generics prescribing for Medicaid programs