FDA Faces Challenges and Changes

For the past few years, the FDA has struggled with a depleted work force, obsolete information technology, and a weak science base, according to its advisory Science Board. A new administration and new FDA leadership provide an opportunity for change. This is "a watershed time" for FDA, says Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER).

Jill Wechsler

The public is concerned about drug quality and imports, industry is struggling with a productivity crisis, and the global financial meltdown may dry up investment for biomedical innovation, Woodcock observed at a meeting sponsored by the Generic Pharmaceutical Association. Her goals are to restore public confidence in the drug regulatory process, capitalize on advances in science and technology, improve postmarket oversight, and make FDA "the recognized leader in drug regulation."

Such a turnaround will not be easy. Rep. Rosa DeLauro (D-CT), who chairs the House Appropriations subcommittee overseeing FDA's budget, asserted at a meeting sponsored by the Institute of Medicine in April that FDA needs "urgent and dramatic reform" because it cannot perform basic functions, such as keeping track of clinical trials, conducting required inspections, and following up on commitments for postmarket studies. DeLauro blames many of FDA's ills on manufacturers and has blocked funding for the Reagan-Udall Foundation until its organizers ensure that it's "not just another tool for industry." She even fears that FDA's Critical Path Initiative may send the message to agency scientists that it's more important to develop methods to support product approval than to objectively evaluate safety and efficacy data.

Overhaul ahead?

Fixing FDA may require major changes. Because the regulatory model for food is very different from that for drugs and biologics, DeLauro and others propose to transfer FDA responsibility for food regulation to a new federal agency that would assume responsibility for multiple programs now spread around dozens of government offices.

To avoid such a disruptive change, agency officials seek to demonstrate their ability to prevent and deal with food contamination problems. They also propose a less radical reorganization that would split FDA into two "directorates," one for food and one for medical products. There is support for such a move from food operators, who feel they play second fiddle to drugs at FDA, and also from some medical product companies that fear being hit by more restrictive food import policies.

Taking the "food" out of FDA is not likely to happen any time soon, as the new Obama administration has much more crucial tasks at hand in the economic and health arenas.

New leader

Improvements in FDA operations, resources, and infrastructure will be shaped considerably by the next FDA commissioner. Lots of names have been circulating in the last month, a sign of the agency's high visibility and importance to the new administration and to Congress. There's hope that FDA's new leader will be named by the Senate in a few months, instead of languishing at the bottom of the White House appointments list.

One priority for the new commissioner is to push for continued growth in appropriated funds in the agency's 2010 budget. "FDA is barely hanging on by its fingertips," attorney Peter Barton Hutt told the House Energy & Commerce Committee a year ago, leading the chorus for increased resources for the beleaguered agency. The Alliance for a Stronger FDA has called for a 20% increase in FDA appropriations to $2.25 billion for next year. That's less than $400 million in new money—a drop in the bucket for most federal agencies.

FDA and industry also hope for less heated attacks from Capitol Hill, with Democrats in control of both the White House and Congress. There may be less inclination to use FDA as a punching bag, says former FDA official Wayne Pines. But he fears that the agency always will be controversial because of the nature of its operations and the scope of products it regulates.

The bottom line for pharmaceutical and medical product manufacturers is whether FDA can approve new therapies for market and oversee product development, production, and marketing in a fair and efficient manner. All the attention on drug safety has raised concerns about a more risk-averse atmosphere at the agency. Manufacturers say they're willing to see if things improve in the coming months before getting too upset about CDER missing user fee deadlines.

"The agency was given a significant number of new authorities and tasks to accomplish and has been hiring and training a lot of new employees," explains Alan Goldhammer of the Pharmaceutical Research and Manufacturers of America (PhRMA). "So it really is this upcoming year that will be critical in looking at performance and benchmarking against PDUFA goals."

One light on the horizon is an increase in the number of innovative new therapies approved by FDA in 2008. The agency experienced a new low in approving only 18 new molecular entities in 2007, and it looked like this past year would be just as bad or worse. But in November, FDA passed the 2007 total and appeared on track to act on several more before year-end. While it's always easier to show gains from a very low starting point, both industry and FDA are happy to consider this a sign of hope for the new year.

Fixing the field

Another priority for a new commissioner is to revive FDA's depleted field inspection force. The Office of Regulatory Affairs (ORA) is in disarray due to years of under-funding and inadequate IT. Most of its top officials have retired or moved to other jobs, leaving the organization without the leadership needed to overhaul the office. District laboratories require new equipment for efficient product analysis, and scientists need infrastructure to conduct risk assessments and analysis.

The explosion in global manufacturing and increased complexity of supply chains, moreover, have increased the potential for counterfeiting and terrorism. A growing number of trials are conducted in other countries, creating new challenges in ensuring adherence to good clinical practices on a global scale.

The surge in food and drug contamination incidents has generated support for FDA's Beyond our Borders initiative. It is establishing overseas branches to better monitor the growing number of foreign manufacturers and clinical sites. The agency opened offices in China in November and plans additional outposts in India, Europe, Latin America, and the Middle East.

But even with more resources and foreign offices, FDA will never be able to inspect every manufacturer and research site on a timely basis. Other approaches may be needed to support field operations, including certification programs for foreign companies, increased reliance on inspections by foreign regulatory authorities, improved risk management of inspection programs, and more efficient technology assay procedures validated by FDA.

Improving IT

Any improvement in field operations will require significant investment in new interoperable information systems. FDA's IT infrastructure is "obsolete, unstable, and lacks sufficient controls to ensure continuity of operations," according to the Science Board. Most agency records are on paper and stored in vast document rooms that are difficult to access. Research laboratories lack the computing infrastructure necessary to conduct appropriate analyses and studies. Many of the agency's network servers have exceeded their recommended service life, and the system lacks security and normal back-up capability.

A reliable, modern IT system could bring considerable efficiencies to FDA operations. Information from large health system databases could uncover signals of adverse events more quickly and effectively. And access to trial data on marketed products could assist reviewers and monitors in evaluating new safety and efficacy issues.

The latest prescription drug user fee program, PDUFA IV, has mapped out a plan for establishing an all-electronic submission platform for drugs and biologics based on format and data standards. FDA expects to spend some $2.5 billion over the next 10 years for new IT and data management services. Ensuring that such information systems fit FDA's complex organization and legal structure will require skilled oversight of vendors, another key challenge for the new commissioner.

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