Change Agent

January 6, 2010
Jill Wechsler, Pharm Exec's Washington Correspondent

Jill Wechsler is Pharm Exec's Washington Corespondent

Pharmaceutical Executive, Pharmaceutical Executive-12-01-2009, Volume 0, Issue 0

FDA Commissioner Margaret Hamburg has a history of health advocacy and a clear mandate to transform the agency. But can she succeed where others have failed?

The role of FDA Commissioner has in recent years become a graveyard for professional reputations, with occupants of the post roundly criticized on everything from undisclosed ownership of drug industry shares to failure to anticipate the presence of salmonella in tomatoes and hot peppers. In terms of impact on the public at large, the post ranks near the top of the executive branch, as the agency's regulatory mandate covers more than a quarter of all consumer-led economic activity in the US. Yet despite this high profile, Commissioners spend much of their time negotiating the boundaries around Congressional mandates that amount to "mission creep" accompanied by ad hoc—and never sufficient—additions to already constrained resources.

In office for six months, Commissioner Margaret (Peggy) Hamburg believes that a more focused public health orientation, diverse management, and an organization-wide commitment to following good science will break the bureaucratic model of "best enough and no more," restoring the FDA as an exemplar of government efficiency and responsiveness. Not surprisingly, Hamburg's main complaint is that she has only 24 hours each day to accomplish all these tasks. But last month she took time from her schedule to discuss her priorities and policies in a one-on-one interview with Pharmaceutical Executive at FDA's campus in White Oak, MD.

— The Editors

One of the first things one notices about Peggy Hamburg is her candor. When the Obama administration rolled in at the beginning of the year, Hamburg admits she was not on any short list of possible FDA commissioners. Although she had been in and out of Washington research institutions and health agencies for 30 years, she was not closely associated 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 management experience at a large city (New York) health agency. The White House wanted an outsider at FDA to tackle food safety, tobacco marketing, and the looming influenza pandemic. The fact that she had no ties to the drug industry was also a plus.

Hamburg sped through the Senate confirmation process last May, with the same candid style in which she readily admitted she was unfamiliar with many of the complex issues raised by the legislators. Her earnest approach drew plaudits from Senators on both sides of the aisle, and her confirmation marked a note of contrast with the recent past: Support was bipartisan and quickly rendered. The new Commissioner kept up the momentum with a well-timed message of solidarity with FDA staff, as well as securing a hefty budget increase.

She and deputy commissioner Joshua Sharfstein co-authored a May 26 editorial in The New England Journal of Medicine that cut through the bureaucratic murk to lay out FDA's central role in protecting public health. It advanced three major policy themes: FDA should (1) help advance science for the products it regulates; (2) assess imported food and drugs more thoroughly; and (3) minimize the risks associated with pharmaceuticals through education, regulation and enforcement. The underlying message is that FDA should not be measured by the number of facilities inspected or drugs approved, but by how well it meets the larger goal of promoting health and preventing illness.

Before Hamburg's confirmation, there was speculation that she and Sharfstein, who ran FDA during the first months of the Obama administration, would divvy up agency oversight and operations, with Hamburg handling food and tobacco, and Sharfstein overseeing drugs and medical products. Again, in a burst of candor, Hamburg moved to dispel such notions, asserting that if confirmed, "I would be the Commissioner."

Policy: The Art of What's Practical

That strong affirmation of singular leadership was good news for pharma. Hamburg's background as an AIDS researcher and in tuberculosis treatment exposed her to the importance of biomedical innovation and drug development in providing doctors with tools to treat serious diseases. After attending medical school in the 1970s, the emerging AIDS epidemic lured her away from academia. During those early days of clinical trials for AIDS treatments, "I decided I wanted to work at the intersection of medicine with broader social, legal, economic and service issues." She saw how important it was to support those discoveries and translate them into "real-world care for the people who need them."

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

More Leeway on Managing Risk?

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 could help detect safety problems and identify fruitful pathways for research that can lead to the 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 that can to distinguish responses and effects on smaller patient groups.

Hamburg promises a more consistent, more integrated approach to evaluating medical products related to personalized medicine, citing plans to issue draft guidance on biomarker qualification and on co-development of drugs and diagnostics. FDA also hopes to spur development of new biomarkers that can identify patient subpopulations most likely to respond to a drug, or to have an adverse reaction.

Better Infrastructure for Good Science

For FDA to support the translation of discoveries into medical products, Hamburg believes it's important to define more effective and efficient regulatory pathways for emerging products. This involves recruiting and retaining top scientists and giving them the facilities and opportunities they need to do their jobs.

It also means stronger collaboration with the scientific community on ways to streamline the drug review process. One idea is to bring together academia, industry, and government at centers for regulatory excellence in order to assess biomarkers and develop new strategies for clinical trial analytics. The Commissioner envies Europe's Innovative Medicine Initiative, which has 2 billion Euros to spend on developing biomarkers, diagnostics, and translational research. Hamburg would like to start a similar interconnected program in the US.

One vehicle for a replenished regulatory science base could be the Reagan-Udall Foundation, which so far has been undermined by a lack of Congressional funding. Hamburg supports it, recognizing that the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention have benefitted from their ability to tap outside resources to support important projects. As a regulatory agency, FDA is "a little bit different," according to Hamburg, and needs clearly defined standards and guidelines to avoid conflicts of interest. But Reagan-Udall, she believes, could be valuable in providing access to new research.

Credible, well-funded regulatory science is equally critical to improving readiness for the next pandemic flu crisis. FDA has taken some of the blame for delays in providing an effective H1N1 vaccine this fall, and Hamburg admits to being frustrated that the production process was not smoother. Still, she prefers to regard the response from FDA and industry as "quite remarkable in terms of how much has been mobilized in response to a previously unrecognized strain of flu virus."

Keeping the Process Honest

Peggy Hamburg is also interested in tackling the sensitive issue of conflicts of interest, and whether eliminating such conflicts is always in the best interest of science. Informed evaluation of new drugs requires input from experts outside the agency, and Hamburg acknowledges the importance of populating FDA advisory boards with people who have the appropriate knowledge.

The problem is that many top experts have relationships with companies developing products. Hamburg notes that a range of stakeholders have advised her not to exclude necessary experts from discussions.

"[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," notes Hamburg.

Commitment to Enforcement

In addition to promoting science and safety, Hamburg wants to enhance FDA's clout in enforcing compliance with its rules. In a high-profile address last August, the Commissioner outlined a more aggressive, more efficient FDA compliance program, and issued the agency's expectations that manufacturers of drugs and medical products will take an equally serious stance in this area. Setting clear enforcement policy, she said, will increase public confidence in FDA oversight, while 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 says, citing problems with product quality, false and unlawful labeling, and misleading advertising. She explained that she wants to limit the back-and-forth between FDA and regulated companies, and encourage fast resolution of enforcement actions.

The "carrot" for manufacturers is a "close-out letter" for companies to inform investors and customers when a facility or product is no longer tainted. The stick for frequent and serious violations is product recalls or seizures, even before issuing a warning letter in situations that raise serious health and safety issues.

FDA's success in spurring compliance "should be measured not by the number of warning letters or injunctions or seizures, [but by] our impact on the health and welfare of the public," says Hamburg. Failure to meet FDA standards not only puts the public at risk, she notes, it is also "jeopardizing the public's confidence in industry."

The message is that FDA is determined to share responsibility for public health problems with industry, as evidenced by the proliferation of post approval safety studies the agency is now requiring as a condition for market authorization.

DTC Promotion and New Media

In her enforcement speech, Hamburg cited an agency crack-down on fraudulent Internet promotion of products that supposedly would protect consumers from swine flu. This development, along with concerns about drug companies posting unbalanced ads on search engines, has prompted a broad initiative to clarify FDA rules for marketing medical products via Web sites and social media.

"FDA is very concerned about fraudulent claims," Hamburg says, adding that US marketers need to "maximize the educational benefits of talking to consumers about health conditions."

Hamburg also understands that some policymakers want to impose a DTC advertising moratorium on newly approved drugs and adopt curbs on drug advertising similar to other nations. Her response is to express curiosity about standards in other countries—including New Zealand, the only other OECD country where drug DTC is officially allowed —and to urge marketers to provide "a stronger educational component" in medicines advertising. Hamburg recognizes that there are many under-treated health problems and poor compliance with medication regimens that could benefit from sound communication by industry. But she also is concerned about consumers "getting accurate and constructive information about important medical conditions. There are opportunities currently being missed," she says.

These issues will be addressed in a broader effort to modernize the rules governing prescription drug promotion, as proposed in FDA's Strategic Plan for Risk Communication unveiled in September. Current rules reflect a time when drug marketing was focused on health professionals, and not consumers, and thus overburden patients with detailed labeling information and technical data that is confusing and often uninformative.

FDA is drafting several possible new approaches, including a one-document method that provides patients with useful written information at the pharmacy. Other priorities are to finalize guidance on presentation of risk information in medical product promotions, and to conclude the ongoing effort to revise the brief summary of drug prescribing information. The overall plan is to evaluate FDA regulation of drug advertising, labeling, and sponsor interactions with healthcare professionals, and weigh the need for new legislation or rule making.

Key Mission: Restoring FDA's Reputation

Improved public confidence in FDA is "mission critical" for Hamburg, mainly because she recognizes that this is essential to securing a steady level of funding and resources. One of her key roles, she acknowledges, is to be an advocate for FDA and its needs. Policymakers must understand the importance of FDA's mission—quite simply, there is no other government agency, academic entity or private organization that can "step in and backstop" for the agency.

"It's astounding to me that given our centrality to the health and well-being of all Americans, we have been under-appreciated and under-resourced for so many years," says Hamburg. Digging out of the agency's depleted funding state will take some time, she acknowledges. "There is no quick fix. It's not a one-time funding increase."

Meanwhile, new legislation continues to expand FDA responsibilities. Congress established a new program to regulate tobacco products, which Hamburg considers vitally important for protecting public health. Support to fund this new responsibility will come through a user fee program, but it remains unclear whether this will be sufficient to meet the needs. Similarly, new food safety legislation will require a major expansion in inspection of food production and imports that may not be fully covered by added revenues. In addition, a required two-year inspection schedule for manufacturers that export to the US would be totally unmanageable and would far exceed proposed fees to support this assignment—all of which Hamburg told Congress a few months ago.

This, in particular, is where FDA is on the hot seat over conflicts of interest. Expansion of user fees to support these and other FDA activities raises concerns about the agency's over-reliance on industry funds. And the issue is sure to resurface as FDA begins to negotiate the next round of the Prescription Drug User Fee Act (PDUFA), which is up for renewal in 2012.

Hamburg does not feel that user fees compromise the integrity of the FDA review process. She believes that it's appropriate for regulated companies to contribute a share, along with public funding through the appropriations process. "What matters to me is that our work is important, and it has to be recognized that our responsibilities outstrip the available resources," says the Commissioner.

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. Hamburg is anticipating such an event, and is working to manage it by leveraging the current goodwill. How?

"We need to explain who we are, what we do, and how we do it so well, given all the constraints."

A New Breed of Regulator: Advocate for Public Health

Like many past FDA commissioners, Peggy Hamburg trained to be a doctor and medical researcher. Born in 1955 to two prominent physicians, she grew up on the Stanford University campus and went to Harvard for college and medical school. Her father, David Hamburg, is a past president of the Institute of Medicine; her mother, Beatrix, was the first African-American woman to earn a medical degree from Yale University. Peggy finished her medical training at Cornell University Medical Center and Rockefeller University in New York. But in the 1980s she disappointed her professors by dropping neuroscience research to go to Washington to work on AIDS treatment policy, first in the HHS Office of Disease Prevention and Health Promotion, and then at the National Institute of Allergy and Infectious Disease at NIH.

The year 1990 marked a critical new path in Hamburg's career when she joined the New York public health department, where she was named commissioner after only a year. There, she learned the tools for successful engagement in a broader agenda rife with politics and the passion of interest groups—not to mention the complexities of coping with large organizations whose broad priorities are often hard to reconcile because they are rooted in social conflict. She recalls her years in New York city government as difficult and demanding due to severe budget constraints, the spread of the AIDS virus, and an emerging tuberculosis epidemic. Among other achievements, she instituted controversial needle-exchange programs, boosted childhood immunization, and established an innovative treatment plan to halt the spread of drug-resistant TB.

A sign of her impact was that she was one of the few officials kept on board when Republican Mayor Rudolph Giuliani took office in 1994. She was elected a member of the Institute of Medicine at that time—one of the youngest ever to earn that honor.

Hamburg returned to Washington in 1997 as assistant secretary for policy and evaluation at HHS during the Clinton administration, where she created a bioterrorism initiative and led planning for pandemic flu response. In 2001 she joined the Nuclear Threat Initiative, a non-profit organization focused on reducing the threat to public health and safety from chemical, biological and nuclear weapons.

Health Reform: Defining FDA's Role

The current healthcare reform issue that involves FDA most directly is the proposal to establish an approval pathway for follow-on biologics. FDA officials have testified that they have the capacity to establish testing and regulatory standards for such products and that they prefer some flexibility in how they evaluate these complex therapies. But it will be a challenge to steer these products through the regulatory process, suggesting approvals may not come as quickly as some in the industry might like.

Commissioner Hamburg also sees FDA playing a supportive role in reforming the nation's healthcare system to provide more quality care and to avoid waste and harm. "Clearly the work that we do affects the availability of critical medical products, which, down the road, affects costs to the health care system," she tells PE. FDA's new Safe Use initiative aims to reduce unnecessary, preventable medical illness and complications due to the misuse or inappropriate use of medications and medical devices. "And that will clearly have an impact on cost and reduce the burden of disease," says Hamburg.

There are expectations that increased funding of comparative effectiveness research could expand the amount of information considered. FDA is "one of many players that makes decisions about the ultimate use of medical products," she notes. Hamburg does anticipate more collaboration with the Centers for Medicare and Medicaid Services to facilitate reimbursement of newly approved medicines. But that is on the back burner until the current health reform debate concludes and an official CMS administrator comes on board, one of the more prominent administration health positions that has not been filled.

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