Struggling with Science: A Critical Look at the US Food and Drug Administration

A report for the US FDA's Science Board says that the agency's failure to keep up with science and information systems is threatening public health.

The US Food and Drug Administration's evaluation methods have not kept pace with major advances in medical devices and use of products in combination, according to an internal review of the agency's scientific activities¹. This is one of the conclusions of the FDA Science Board, an advisory board to the FDA commissioner, which says in a report that scientific expertise within the agency has been seriously eroded. Moreover, the report criticises the agency's potentially dangerous in-house information systems, describing them as “obsolete” and “unstable”. Large budget increases and a substantial restructuring in management, it says, are needed to avoid failure of the agency's mission to protect the public.

Lead author Gail Cassell, chair of the Science Board's Science and Technology Subcommittee, spelled out the report's findings to FDA commissioner Andrew von Eschenbach and deputy commissioner Janet Woodcock at an FDA Science Board session². Dr Cassell, who is also vice president of scientific affairs at drugs company Eli Lilly, listed the agency's principal deficiencies, which are described below.

Science

The pace of scientific discovery and the complexity of new products have left the agency far behind as its staff have struggled with increased workload and a chronic shortage of funds. These combined pressures have led to the loss of some of the agency's best scientists, says the report. “Science at the FDA is in a precarious position,” says Dr Cassell. She warns that the agency suffers from “serious scientific deficiencies” and is unable to meet either current or emerging regulatory responsibilities. “Resources have not increased in proportion to the demands, with the result that the scientific demands on the agency far exceed its capacity to respond.”

The problems are not solely due to staff shortages, however. The report says that the agency's weak management structure has also left it without any coherent scientific structure and vision. “Today, not only can the agency not lead, it cannot even keep up with the advances in science,” says Dr Cassell. Though the report regards the FDA's food branches (the Center for Food Safety and Applied Nutrition and the Center for Veterinary Medicine) as most at risk, it also identifies several new medical technologies that are particularly challenging the FDA, including systems biology (genomics and proteomics); nanotechnology; cell-based and tissue-based products; regenerative medicine; and combination products. The only exceptions to the “substantial weaknesses across the agency” are certain drug and medical device review functions that are separately funded by industry user fees, the report adds.

IT infrastructure

The FDA's IT infrastructure “…lacks sufficient controls to ensure continuity of operations or to provide effective disaster recovery services”, says the report. Several of its critical information systems are “inefficient, cost-intensive and prone to promote errors in regulatory science due to the inability to access, integrate and analyse data”. Calling the situation “extremely disturbing, at best problematic and at worst dangerous”, Dr Cassell notes that the FDA has no systems to store data from clinical trials or adverse event reporting. As a result, most of its vast stocks of critical data “reside in large warehouses sequestered in piles and piles of paper documents” unprotected by any effective security or backup systems.

Data exchange

The agency has no clear processes for exchanging data either internally or with partner organisations, according to the report. The result is that it “cannot credibly process, manage, protect, access, analyse and leverage the vast amounts of data that it encounters”. The FDA is trying to move to an “enterprise model” in which critical systems will be concentrated in secure data centres. But progress has been slow: it is still only halfway through this migration and many components remain scattered around the agency. “This information crisis is putting the FDA's mission at risk,” the report warns.

Other problems

Other problems include a lack of expertise in statistical methods and risk:benefit analysis; a failure of the agency's separate centres to collaborate with each other and with external institutions; and an “inflexible” human resources policy that has led to staffing difficulties, with turnover rate for FDA science staff in key areas running at twice that of other government agencies.

Praise for Critical Path Initiative

The report does praise some aspects of the FDA's science-based work, in particular the Critical Path Initiative. However, the “constrained resources and lack of adequate staff” responsible for the agency's defects have forced it into a position of fire-fighting instead of pursuing a culture of proactive regulatory science, says Dr Cassell.

Proposed solutions

Budget increase

The report's principal recommendation, naturally, is a very substantial increase in the FDA's budgets, even though Dr Cassell and her colleagues acknowledge the Bush administration has virtually ruled this out already. In his recent executive order announcing an Inter-Agency Working Group on Import Safety, President Bush stated that the current system must be fixed “within available resources”³.

But the report insists: “We can state unequivocally that the system cannot be fixed within available resources … the FDA can no longer fulfil its mission without substantial and sustained additional appropriations.” If the agency's chronic underfunding is not reversed immediately, it is in jeopardy of losing its remaining dedicated staff, the report warns: “The extraordinary efforts of these committed FDA staff members are the very reason further catastrophic food and drug events have been averted.”

By comparing FDA budgets with those of the similarly science-focused Centers for Disease Control, Dr Cassell's team estimates that the FDA's existing $200 million annual IT budget should be raised to $500 million. The report cites an Institute of Medicine analysis estimating that a system allowing FDA staff to access the necessary databases, establish critical external collaborations and perform essential studies, will cost $350 million⁴.

This would pay for “large-scale, sustainable data sharing infrastructures to support clinical trials and pharmacovigilance, quality activities, registration activities, and manufacturing life-cycle activities such as electronic product coding to prevent manufacturing fraud”. It would also allow the agency to extend its active surveillance of drugs and biologics to cover medical devices, animal drugs and possibly even foods.

To remedy the damage to the agency's science base will cost even more. Again the report cites IOM figures, indicating that a minimum of $350 million extra is needed immediately to address urgent safety needs⁵. Moreover, the US Grocery Manufacturers/Food Products Association has demanded a further $450 million over five years to ensure food safety, while the Coalition for a Stronger FDA wants a 15% increase in appropriations every year for the next five years, leading to a $2.8 billion annual budget by 2013 compared with $1.6 billion in 2007⁶. In the light of recent safety panics, the authors suggest that even that would not be enough: a more reasonable target, they say, would be a doubling of the budget.

Restructuring

However, they also concede that resurrecting the FDA's science base will need not just money but also a significant restructuring. The report recommends “in the strongest way” the creation of a centralised science infrastructure directed by a newly appointed deputy commissioner and a chief scientific officer, with authority over all science activities at the agency, including control of the associated budgets, as well as extensive collaborations with outside bodies. The new organisation would include an “incubator” department to develop means of regulating innovative scientific disciplines like systems biology - especially a formal genomics programme.

The report ends by urging the FDA to develop a business plan to implement the above strategy in time for the 2009 budget process.

The FDA's Science Board voted unanimously on 3 December 2007 to accept the entire report, and said it will be seeking comment on the report, both from FDA leaders and from the public⁷.

There is some heavyweight political backing for boosting FDA budgets, particularly if accompanied by management restructuring. As soon as the report appeared, veteran congressman Henry Waxman (Democrat - California), chairman of the House Oversight Committee, wrote to US secretary of state for health Michael Leavitt and Jim Nussle, director of the Office of Management and Budget, urging them to request adequate funds and resources for the FDA. Representative Waxman said the report “paints a dire picture of a chronically underfunded agency” whose “grave deficiencies” were now endangering public health⁸.

Sheila Burke, who chaired the 2006 Institute of Medicine inquiry into drug safety⁹, dismissed suggestions that the FDA was “crying wolf” in order to boost its budgets. “There is clear evidence established from different sources, including the Government Accountability Office as well as the IOM, indicating that this report is in fact accurate,” she said¹⁰: “Given the current budget battles on Capitol Hill, it will be tough to get the extra funding, but not without precedent.”

Dr Cassell commented that FDA leaders would need to evaluate the board's findings before addressing resource issues. She noted that Secretary Leavitt has been “very supportive of getting FDA more money in President Bush's budget request for the 2009 financial year”. There would be, Dr Cassell said, “more adverse drug and device events that go unnoticed”, if the agency failed to get the $350 million needed to implement the surveillance system recommended by the IOM.

“Without more resources, we are likely to start to see more frequent and more lethal food problems, both domestic and imports; the rest of the world pulling away from [the US] and dominating new technology such as nanotechnology; and more problems in lower-profile fields like cosmetics, pet food, nutritional supplements, and antibiotic resistance,”.she said. Dr Cassell also predicted that drug and device approvals would continue to slow, even given the benefit of user fees¹¹.

References

1. FDA Science Board, FDA science and mission at risk, November 2007, www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4329b_02_01_FDA%20Report%20on%20Science%20and%20Technology.pdf

2. FDA Science Board meeting documents, 3 December 2007, www.fda.gov/ohrms/dockets/ac/oc07.htm

3. White House Executive Order: Establishing an interagency working group on import safety, www.whitehouse.gov/news/releases/2007/07/20070718-4.html

4. Institute of Medicine report, The Future of Drug Safety, 2006, National Academies Press, Washington DC, www.iom.edu/CMS/3740/24155/45823.aspx

5. Institute of Medicine report, Challenges for the FDA, 2007, National Academies Press, Washington DC, www.iom.edu/CMS/3740/24155/45823.aspx

6. FDA Coalition press release, 6 February 2007, www.fdacoalition.org/news.php

7. Personal communication, FDA press office, 7 December 2007

8. Letters from Henry Waxman to von Eschenbach, Leavitt and Nussle, 3 December 2007, http://oversight.house.gov/story.asp?ID=1644

9. See Reference 4

10. Personal communication, Sheila Burke, 7 December 2007

11. Personal communication, Gail Cassell, 10 December 2007