Regulatory Beat: FDA Moves to Renew User Fees and Promote Preparedness

The Food and Drug Administration's Prescription Drug User Fee program (PDUFA) has to be reauthorized by Oct. 1, 2007, and all the interested parties are fine-tuning their wish lists for "improvements." Although some consumer advocates and their Congres-sional allies blast user fees for extending industry control over the drug approval process, FDA officials, pharma companies, and patient disease groups applaud the program's success in ending "drug lag" and speeding new drugs and biotech therapies to market.

Jill Wechsler

FDA held a meeting in November to open the PDUFA 4 debate. Acting Commissioner Andrew von Eschenbach termed PDUFA reauthorization "critical" to FDA's ability to make "biomedical innovation a reality." Deputy Commissioner Janet Woodcock described how user fees have been expanded twice since 1992 to support a broad range of FDA activities, from early discovery to post-market surveillance, including improvements in agency information systems.

MORE FOR SAFETY

Now FDA wants to use fee revenues to further extend drug safety oversight and to review direct-to-consumer (DTC) advertising before it goes public. The agency also would like to devote some of its added resources to improving the increasingly complex drug development process, as part of its Critical Path Initiative. An FDA white paper describes the agency's case for increas-ing appropriated funds, in addition to user fees, to support the agency's expanding public health responsibilities. [For more information, see the white paper, available at www.fda.gov/oc/pdufa.]

FDA cites an expanded workload to justify fee revisions: while new drug applications (NDAs) and biologics license applications (BLAs) have been fairly flat, efficacy and manufacturing supplements continue to rise. FDA struggled last year to schedule and plan for more than 2,000 industry-requested meetings and to assess nearly 350 special research protocols, many involving new carcinogenicity and stability test methods.

FDA has launched similar discussions involving reauthorization of user fees for medical device manufacturers, which also expire in 2007. Officials at FDA's Center for Devices and Radiological Health also seek to use more of the fees collected under the Medical Device User Fee and Modernization Act of 2002 for postmarket surveillance, a proposal gaining momentum following recent safety crises involving pacemakers and defibrillators.

NO CHRISTMAS TREES

Pharma and biotech companies want to renew PDUFA but limit fee increases and the use of fee revenues for activities unrelated to drug development and market approval. Sponsors now pay almost $800,000 to file an NDA or BLA, which spurs proposals for more waivers and reduced fees for small companies and orphan drug developers.

The broader goal is to prevent a PDUFA reauthorization bill from becoming a "Christ-mas tree" loaded with legislation peripheral to the drug approval process. Measures to encourage development of follow-on biologics, to establish new drug safety oversight arrangements, to mandate completion of post-approval studies, and to boost oversight of DTC advertising are just some of the popular proposals circulating on Capitol Hill.

However, manufacturers do support efforts to link PDUFA reauthorization to legislation that renews incentives for studying drugs in pediatric populations, which also is up for reauthorization in 2007. The six-month patent extensions have been a boon for pharma companies, while also generating important pediatric labeling information.

Before talking about more fees, Abbott Senior Vice President Bruce Burlington, representing Pharma-ceutical Research and Manufacturers of America at the November meeting, urged further discussion about whether current user fee revenues are wisely spent. Industry experts expressed support for continued development of FDA computer information systems; however, Alison Lawton of the Biotechnology Industry Organization (BIO) questioned whether FDA's continuous market application pilot programs have been successful.

SUPPORT FOR SAFETY

Lawton of BIO also suggested that one way to ensure drug safety is to improve FDA's evaluation of trade names. This may fit FDA's desire to make more user fee revenues available to support FDA postmarketing surveillance and risk management activities, which have been under intense scrutiny by Congress and the public in recent years. Under PDUFA 3, FDA can allocate user fee revenues for drug safety monitoring during the first two years a new drug is on the market (three years for potentially dangerous medications). However, the agreement covers only new drugs, not safety issues related to products approved five or ten years ago, such as COX-2 inhibitors or antidepressants.

More flexibility could provide resources for FDA to implement some of its recently proposed initiatives to increase product surveillance, improve its ability to communicate safety concerns to the public, and better organize its internal post-marketing oversight operation. However, pharma companies and health professionals have voiced reservations about some of these proposals. At a two-day meeting in December on FDA methods for communicating drug risk information, manufacturers, pharmacists, and other parties complained about the proliferation of agency "risk communication tools." In addition to labeling changes, FDA may announce safety concerns through press releases, talk papers, public health advisories, MedWatch safety updates, and information sheets for healthcare professionals and patients.

Manufacturers are particularly upset by FDA's new plan to post "emerging" drug safety information on a new Drug Watch website. Industry representatives fear that such actions would confuse both consumers and physicians about whether a drug is unsafe and should no longer be prescribed. Agency officials now say they will "go back and rethink" the Drug Watch Plan, but some type of early-safety-warning system is likely.

PROTECTING AGAINST PANDEMICS

At the PDUFA meeting, Jesse Goodman, director of the Center for Biologics Evaluation and Research, noted that user fees don't cover CBER oversight of tissues, blood banks, or public health and safety assignments. At the same time, CBER is charged with spurring access to new vaccines and countermeasures to protect the nation against looming epidemics and bioterrorism threats. The Bush administration unveiled a $7.1 billion Pandemic Influenza Plan in November 2005 that includes a $2.8 billion "crash program" to revitalize vaccine manufacturing in the US. One aim is to support a shift from egg-based flu vaccine production to advanced cell-culture approaches able to produce new flu vaccines in six months. Another $1.5 billion would buy 40 million vaccine doses by 2009; $1 billion would stockpile enough antivirals to treat 25% of the population.

Congress approved a down payment on the program in December by adding $3.8 billion for pandemic preparedness to the $453 billion 2006 defense appropriations bill. The legislation does provide $20 million to support FDA research and oversight of vaccine production, but this is a relatively paltry amount that will barely cover the cost of monitoring vaccine manufacturing facilities in the US and abroad. The 2004 flu vaccine crisis required FDA officials to spend weeks overseeing vaccine quality and inspecting manufacturing sites, while also engineering accelerated approval for new sources of supply.

The most controversial provision in the defense funding bill – and one of critical importance for industry – provides liability protection for manufacturers of pandemic countermeasures. Democrats attacked the measure as excessively broad, even though manufacturers did not get all that they wanted. BIO termed the bill "balanced" and important for rebuilding the nation's vaccine infrastructure, despite its failure to provide additional patent incentives for new product development. Strong opposition from generics makers blocked adoption of a controversial "wild card" exclusivity provision that would have granted patent extensions on commercial products in exchange for producing low-profit countermeasures.

An FDA Rapid Response Team will coordinate agency pandemic preparedness activities with industry and other public health agencies. One task is to detect and manage production problems that could block adequate supplies of antivirals and vaccines. Among other responsibilities, the team can authorize other firms to manufacture a patented product for emergency use. All these activities will further stress FDA's resources, especially if a public health crisis does appear.

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