Revitalization, Reform Ahead for The FDA

The US Food and Drug Administration 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 the FDA, says Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER). The public is concerned about drug quality and imports, industry is caught in a productivity crisis, and the global financial meltdown may dry up investment for biomedical innovation, she observes. Her goal is to restore public confidence in the drug regulatory process, capitalize on advances in science and technology, improve postmarket oversight, and make the FDA "the recognized leader in drug regulation."

Jill Wechsler

Such a turnaround will not be easy. Rep. Rosa DeLauro (D-CT), who chairs the House Appropriations subcommittee that oversees the FDA's budget, asserted at a meeting sponsored by the Institute of Medicine in April, that the FDA needs "urgent and dramatic reform." The agency cannot perform basic functions, she said, such as keeping track of clinical trials, conducting required inspections, and following up on commitments for postmarket studies. "FDA is barely hanging on by its fingertips," attorney Peter Barton Hutt told the House Energy & Commerce Committee a year ago, joining the chorus seeking increased resources for the beleaguered agency.

IMPROVING OPERATIONS

Fixing the FDA may require a major overhaul to better fit the global world of pharmaceutical and food production. Because the regulatory model for food is very different from that for drugs and biologics, DeLauro and others propose to transfer the FDA's 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 are taking steps to demonstrate their ability to prevent and deal with food contamination problems. They also propose a less radical reorganization that would split the FDA into two "directorates," one for food and another for medical products. There is support for such a move from food operators, who feel they play second fiddle to drugs at the 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. But if Congress follows through on proposals to authorize the FDA to regulate tobacco, that could provide an opportunity for broader organizational changes.

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 is considerable hope that the FDA's new leader will be named and confirmed by the Senate in a few months.

One priority for the new commissioner is to push for continued growth in appropriated funds in the agency's 2010 budget. The Alliance for a Stronger FDA has called for a 20% increase in the 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.

A prime goal for biotech and pharmaceutical manufacturers is for the FDA to approve new therapies for market and oversee product development, manufacturing, 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 that may slow authorization of new products.

But there's light on the horizon with an increase in the number of innovative therapies approved by the FDA in 2008. The agency experienced a new low in approvals of new molecular entities (NMEs) in 2007, and it looked like this past year would be just as bad or worse. But in November, the FDA passed the 2007 approval total of 18 NMEs and appeared on track to act on several more before year-end. Although it's always easier to show gains from a very low starting point, both industry and the 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 the FDA's depleted field inspection force. The Office of Regulatory Affairs (ORA) is in disarray because of years of under-funding. Most of its top officials have retired or moved to other jobs, leaving the organization without the leadership needed to make necessary operational changes. 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. Heparin was "a wake-up call," says Woodcock. It "brought home the need for vigilance throughout the supply chain" and highlighted the importance of manufacturing controls.

The FDA's field force operates on a 70-year-old model that relies on generalists who inspect a vast range of operations, from vegetable growers to antibiotic producers. With the emergence of complex production methods for biologics, the FDA established an elite Team Biologics with expertise in biotech manufacturing to inspect those sites. CDER has sought to replicate that model by developing a highly trained pharmaceutical inspectorate to evaluate drug manufacturers.

The surge in food and drug contamination incidents in the last two years has generated support for the FDA's Beyond Our Borders initiative that is establishing overseas branches to better monitor the growing number of foreign manufacturers of products destined for the US. The agency opened offices in China in November and plans additional outposts in India, Europe, Latin America, and the Middle East to track local political and economic developments and be on the spot if problems arise.

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

IMPROVING INFORMATION TECHNOLOGY

Any improvement in field operations will require significant investment in new interoperable information systems. The 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 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 backup capability.

A reliable, modern IT system could bring considerable efficiencies to the FDA operations. Instead of sending inspectors to check manufacturing operations and product quality, cutting-edge technology could allow the agency to position remote sensing devices at plants able to detect product contamination or diversion in real time. Information from large health-system databases could uncover signals of adverse events more quickly and effectively. And access to clinical 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 based on format and data standards. The FDA expects to spend approximately $2.5 billion over the next 10 years for new IT systems. Ensuring that such information systems fit the agency's complex organization and legal structure will require skilled oversight of vendors, which is another challenge for the new commissioner.

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