Perspective

Reviving the FDA

Susan Okie, M.D.

N Engl J Med 2010; 363:1492-1494October 14, 2010

Article

Approaching the end of her first year as commissioner of the Food and Drug Administration (FDA), Dr. Margaret Hamburg remarked that, despite past experience with government bureaucracies, she is struck by how hard it is to make her agency act quickly. “You feel it differently at the FDA — how long it takes to move things through the system,” she told an audience at the Institute of Medicine (IOM) in February. “The process of regulation does not allow you to respond in a timely way to emerging science or to other important emerging concerns.” The FDA's principal deputy commissioner, Dr. Joshua Sharfstein, put it more bluntly in a recent interview: “I keep a list of things that I wish were moving faster and a list of things moving at just the right speed, and there's nothing on the second list.”

Finding ways to make the FDA more nimble and proactive, restoring its credibility and refocusing staff on its public health mission, persuading Congress to boost funding for its expanding portfolio of responsibilities, sharpening its ability to deal with new science and globalization — these priorities have occupied Hamburg and Sharfstein during their first year. Their agency regulates products accounting for some 25% of U.S. consumer spending, and its recent concerns have included major recalls of over-the-counter pediatric medications and salmonella-contaminated eggs, debates over direct-to-consumer genetic testing and the safety of the one-time blockbuster diabetes drug rosiglitazone, the implementation of a 2009 law making the agency responsible for tobacco regulation, and efforts to make food-package labeling more evidence based. While responding to such issues, they have also launched initiatives to clarify and standardize processes for evaluating drugs and medical devices and to make more information public — efforts that could lead to lasting changes at the agency.

Hamburg has spent hundreds of hours meeting with interest groups — patient organizations, consumer groups, scientific organizations, industry officials — and visiting key members of Congress to build alliances. “When I took this job, I wasn't sure whether every single day I'd be beaten up by some constituency or another,” she recalled. Instead, “I have encountered a sense of real eagerness . . . to support the FDA in its mission.”

Hamburg and Sharfstein have also met with groups of FDA employees, familiarizing themselves with the agency's operations and trying to encourage a more proactive attitude among its scientists, regulators, and inspectors. “We are taking a hard look at how we can be creative within [the agency's] legal and regulatory requirements,” Hamburg said. Sharfstein said that when employees described a problem, they frequently added, “and here's what we are allowed to do about it.” “The question we would come back with,” he said, “is, `What do you think the right thing to do is from a public health perspective?'”

Such discussions have prompted measures to accelerate responses to urgent health threats. For example, under a new process called a risk control review, a field inspector who detects such a threat can initiate a meeting of key FDA employees to discuss possible emergency action. Previously, an inspector would file a report that had to work its way through several layers of bureaucracy. Last fall, to avert large-scale food-poisoning outbreaks, the FDA began requiring anyone in the food industry who becomes aware of a contaminated product to report the problem to an agency registry. “Then we can intervene” before a major outbreak occurs, Sharfstein said. More than 100 food-safety reports were submitted during the program's first 7 months.

In nonemergency situations, FDA officials have taken what Sharfstein called “nuanced” actions that stopped short of product recalls but achieved a desired result. For example, last year, when an industry-backed food-labeling campaign resulted in green check marks (signifying “better for you” products) on the front of sugar-laden breakfast cereals and high-sodium frozen meals, the FDA issued a letter to the program's managers, cautioning that it intended to monitor the impact on consumers' purchasing decisions. Major food companies stopped participating, and the program was suspended.1 The agency is currently developing guidelines for front-of-package claims.

For years, critics have been charging that the FDA's internal culture stifles dissent, that regulators are under pressure to approve drugs and medical devices quickly, and that the agency is too slow to act on safety concerns — though other critics believe “that the pendulum has swung too far to the safety side and that we're not recognizing the potential” of new products, says Sharfstein. So the new leadership has been reexamining the processes for making decisions about the safety and effectiveness of drugs and medical devices. In the latter area, much attention has focused on the device center's 510(k) clearance process, which allows new devices judged “substantially equivalent” to others already on the market to be approved without extensive clinical trials. Critics point to devices approved in this way that went on to fail or to injure patients. Last year, a scathing internal FDA review identified numerous flaws in the process that led to clearance of the ReGen Menaflex, a mesh implant for use in repairing chronic knee injuries.2 Officials in the FDA's Center for Devices and Radiological Health adopted the reviewers' recommendations for reform and developed a clearer, fairer decision-making process. This August, the device center issued two reports proposing other changes to the 510(k) process, including a requirement that companies submit a summary of all available scientific information about safety and efficacy when a device is reviewed.3 The agency is awaiting a report next year by an IOM panel that is likely to recommend additional reforms.

Hamburg has also appointed an internal task force to review the way decisions about drug safety are made at the Center for Drug Evaluation and Research (CDER). In recent years, researchers in CDER's Office of Surveillance and Epidemiology have repeatedly claimed that staffers in the center's Office of New Drugs are too focused on approving new products and are reluctant to consider removing drugs from the market when safety concerns arise. Agency officials publicly acknowledged bitter dissent among CDER staff during a July advisory committee meeting to evaluate cardiovascular risks associated with rosiglitazone, and Hamburg took the unusual step of addressing committee members at the beginning of the meeting, urging them to “follow the science” in deciding whether to recommend removing the drug from the market. Ultimately, in a decision announced on September 23, the FDA took action to severely restrict the use of rosiglitazone (see Perspective article by Woodcock and colleagues in this issue). The agency also conducted a review of the status of required postmarketing safety studies and discovered that far more of them have been initiated than had previously been known (see graphsStatus of the 1531 Backlogged Postmarketing Safety Studies of FDA-Approved Drugs and Biologic Agents.).

In a separate approach to ensuring product safety, the FDA has contracted with Harvard Pilgrim Health Care to develop and test a pilot version of its Sentinel System, a data-mining system required by a 2007 law that will be used to analyze electronic medical records from large private health care systems in order to answer safety questions. The agency is also awaiting a report, due next spring, from an IOM panel about the strengths and weaknesses of various kinds of studies for evaluating drug safety.

Focusing on longer-term priorities, Hamburg has been advocating for increased FDA funding and trying to forge partnerships that will help her agency fulfill its mission, particularly in response to emerging science and technology and to globalization. “We are behind where we need to be,” she said. “Our resources are outstripped by our responsibilities. . . . I think we have to recognize that there is a continuing need for expansion of investment, as well as creativity about how we do our job.” President Barack Obama's proposed 2011 budget contains funding for regulatory science at the FDA, and Hamburg said the agency hopes to collaborate with scientists in academia and industry, as well as other federal health agencies, on research and training in such areas as biomarkers, bioimaging, clinical-trial analytics, and pharmacoepidemiology.

On the globalization front, to grapple with the expanding task of ensuring the safety of products or components of products made overseas, the agency is introducing a risk-based strategy for targeting priority inspections, “based on the type of commodity, the history of the companies involved,” and other relevant information, Hamburg said. FDA officials are also discussing with other countries' regulatory agencies “how we can share the results of inspections, so we don't have the situation that does occur now, where one facility in China or India might be inspected multiple times a year by multiple regulatory authorities, and then other facilities don't get inspected for years.” In addition, officials in the United States and elsewhere are discussing strategies, such as training programs, exchanges, and research collaborations, for strengthening quality-control and regulatory capacity in developing countries. Hamburg says she sees this effort “as a real win–win” for consumers, industry, and developing-country economies. In the global regulatory arena, the agency's “input is most welcome,” she added; after all, despite criticism and growing pains here at home, “overseas, the FDA is still considered the gold standard for a regulatory agency.”

Disclosure forms provided by the author are available with the full text of this article at NEJM.org.

This article (10.1056/NEJMp1009686) was published on October 6, 2010, at NEJM.org.

Source Information

Dr. Okie is a medical journalist and a clinical assistant professor of family medicine at Georgetown University School of Medicine, Washington, DC.

References

References

1. 1

   Neuman W. Food label program to suspend operations. New York Times. October 24, 2009:B1.
   

2. 2

   Review of the ReGen Menaflex: departures from processes, procedures, and practices leave the basis for a review decision in question: preliminary report. Silver Spring, MD: Food and Drug Administration, September 2009. (http://www.fda.gov/downloads/NewsEvents/PublicHealthFocus/UCM183642.pdf.)
   

3. 3

   CDRH preliminary internal evaluations. Silver Spring, MD: Food and Drug Administration. (http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHReports/ucm220272.htm.)
   

4. 4

   Final report on the postmarketing requirement/postmarketing commitment backlog review. Silver Spring, MD: Food and Drug Administration, April 10, 2009. (http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/ucm180982.)
   

Citing Articles (3)

Citing Articles

1. 1

   Kramer, Daniel B., Xu, Shuai, Kesselheim, Aaron S., . (2012) Regulation of Medical Devices in the United States and European Union. New England Journal of Medicine 366:9, 848-855
   Full Text

2. 2

   Kevin V. Blake, Stefanie Prilla, Sophie Accadebled, Marie Guimier, Monica Biscaro, Ingemar Persson, Peter Arlett, Stella Blackburn, Henry Fitt. (2011) European Medicines Agency review of post-authorisation studies with implications for the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. Pharmacoepidemiology and Drug Safety 20:10, 1021-1029
   CrossRef

3. 3

   Linda S. Plank. (2011) Governmental Oversight of Prescribing Medications: History of the US Food and Drug Administration and Prescriptive Authority. Journal of Midwifery & Women's Health 56:3, 198-204
   CrossRef