Science and Research Top FDA Priorities

In her first year at the helm of the Food and Drug Administration, Margaret (Peggy) Hamburg has worked to reposition FDA as a public health agency able to ensure the safety and quality of the nation's food supply and medical products. FDA is revising medical device oversight, establishing a new tobacco center, and engineering a major overhaul of food monitoring and inspections. A priority for Hamburg is to bring important new drugs and medical products to patients, which requires more collaboration with industry and academia to develop biomarkers and advance personalized medicine.

Jill Wechsler

The commissioner also has been waving a big stick to emphasize the agency's role as a vigorous enforcer of regulations and standards to keep unsafe products off the market.

As the lead advocate for FDA, Hamburg feels a responsibility to actively explain its rules and operations. She is a featured speaker on the meetings and conferences circuit, highlighting the need for more "transparency" in agency regulatory decisions and actions to regain public trust. A "Safe Use" campaign aims to reduce medication errors and adverse events by encouraging appropriate drug utilization.

All these initiatives require more resources, and it's up to Hamburg to obtain adequate funding from a penny-pinching administration and skeptical Congress. Digging out of the agency's depleted funding state will take some time, she acknowledged in a conversation with Applied Clinical Trials. "It's not a quick fix. It's not a one-time funding increase."

Hamburg honeymoon

When the Obama administration rolled into Washington last year, Peggy Hamburg was not on any short lists of possible FDA commissioners.

Although she had been in and out of Washington research institutions and health agencies for 30 years, she was not associated closely with FDA, with clinical research or with food and drug regulation. But she had top credentials in the public health community, was an expert in bioterrorism, and presented an attractive mix of medical training, government service, and managing a large city health agency. The White House wanted to bring in an outsider to head FDA to tackle food safety, tobacco marketing, and the looming influenza pandemic. No ties to the drug industry was a plus, along with an academic and public health background that pleased Senate leaders.

After speeding through the Senate confirmation process last May, the new commissioner started off on a positive note, publicly praising FDA staffers and presenting a hefty budget increase. She and Deputy Commissioner Joshua Sharfstein coauthored an editorial in the New England Journal of Medicine (May 26, 2009) that lays out their major themes: FDA should help advance science for the products it regulates, assess imported food and drugs more thoroughly, and minimize the risks associated with pharmaceuticals through education, regulation and enforcement.

Taking risks

That was good news for sponsors of clinical trials. Hamburg's experience in AIDS research at the National Institutes of Health and in tuberculosis treatment as New York City public health commissioner in the 1990s exposed her to the importance of biomedical innovation and drug development in providing doctors with tools to treat serious diseases.

Hamburg also understands the nuances in assessing risk in bringing new drugs to market. An approval process that is too fast may fail to detect safety problems, while one too slow could delay treatments for patients with life-threatening diseases. Hamburg considers it "a false dichotomy" to separate safety from innovation, and that promoting public health involves finding the right balance for both. FDA can do more in the area of drug safety, she suggests, but not at the expense of delaying innovation. As she and Sharfstein state in the NEJM article, "Some benefits are not worth the risk; some risks are worth taking."

FDA may be willing to take more risks, Hamburg says, due to additional authorities provided by the FDA Amendments Act (FDAAA). The ability to restrict distribution and to better detect safety problems of newly approved drugs may support earlier approval of important medications. And more collaboration with other government agencies, industry, and patients can help detect safety problems and identify "fruitful pathways" for research that can lead to the eventual approval of treatments.

To assess drug risks and benefits appropriately, FDA needs to fully understand the science behind emerging research and products. Hamburg is concerned that the nation's huge investment in biomedical research has not been balanced by comparable support for regulatory science. FDA is at "the nexus of translating genomics into targeted therapies and new diagnostics," she noted at a symposium on the "Future of Personalized Medicine" in October. This requires moving beyond randomized controlled clinical trials to new test methods able to distinguish responses and effects on smaller patient groups.

Hamburg promised a more integrated approach to evaluating medical products related to personalized medicine, citing plans to issue draft guidance on biomarker qualification and on codevelopment of drugs and diagnostics this year.

Defining more effective and efficient regulatory pathways for emerging products also involves recruiting and retaining top scientists and giving them the facilities and opportunities they need to do their jobs, Hamburg says. It also means stronger collaboration with the broader scientific community on ways to streamline the drug review process. One idea is to bring together academia, industry, and government into centers for regulatory excellence to assess biomarkers and their use and to develop new strategies for clinical trial analytics.

A vehicle for expanding FDA's regulatory science base could be the Reagan-Udall Foundation, which so far has been undermined by a lack of funding from Congress. Hamburg would like to build support for the organization, recognizing the need for clearly defined standards and guidelines to avoid conflicts of interest.

Informed evaluation of new drugs requires input from experts outside the agency, and Hamburg acknowledges the importance of populating FDA advisory boards with individuals who have the appropriate knowledge. The problem is that many of the top experts also have had relationships with companies developing products, which raises conflict-of-interest issues.

Hamburg notes that a range of stakeholders have advised her "not to go too far and exclude necessary experts from discussions." Transparency can help, she observes, but the challenge is "to find the right balance of having critical expertise at the table and avoiding conflicts of interest that distort the assessment of science."

Stronger regulatory science could improve vaccine testing and production for the next pandemic flu crisis. FDA has taken some of the blame for delays in providing an effective H1N1 vaccine last fall, and Hamburg admits to being disappointed that the production process was not smoother. But she prefers to regard the response from FDA and from industry as "quite remarkable in terms of how much has been mobilized in response to a previously unrecognized strain of flu virus." Some of the disappointment may stem from over-optimism in predicting how much vaccine would be available and when. "Sadly, we know that it's the nature of manufacturing vaccines to have some unexpected delays, and it's the nature of science to have unanticipated problems emerge."

Cracking down

In addition to promoting science and safety, Hamburg wants to enhance FDA's clout in enforcing compliance with its rules. She promotes a more aggressive and more efficient FDA compliance program to increase public confidence in FDA oversight, while also establishing a level playing field for industry and keeping unsafe and fraudulent products off the market.

Too many serious violations "have gone unaddressed for far too long," Hamburg said in a major address last August, citing problems with product quality, false and unlawful labeling, and misleading advertising. FDA's success in spurring compliance "should be measured not by the number of warning letters or injunctions or seizures," she said, but by "our impact on the health and welfare of the public." Failure to meet FDA standards means that a company is "putting the public at risk," she stated, and also "jeopardizing the public's confidence in your industry."

So far, Hamburg has enjoyed strong support from the Obama administration, Congress, and FDA's many constituencies. But at some point there will be a food contamination crisis or a drug safety problem on her watch, accompanied by a wave of finger-pointing. For now, Hamburg is making a strong effort to "speak out and explain who we are, what we do," an approach that she hopes will build support to give FDA the resources it needs to "fulfill our important mission."

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