Science to the Rescue

FDA wants more respect and less second-guessing of its regulatory actions. The strategy is to build in-house scientific expertise and improve evaluation methods so that a decision to approve a drug for market—or to require postmarketing studies—doesn't draw criticism on the political front or challenges from experts with differing opinions.

Jill Wechsler

Strengthening FDA's science base has been a leading theme for Commissioner Margaret Hamburg since she took the helm at the agency a year ago. Hamburg has gained modest recognition for this effort from the Obama administration, which earmarked money for a small science program in the 2011 budget plan, and from the National Institutes of Health (NIH), which is funding research on ways to improve the science of evaluating new drug safety and efficacy.

Up until now, the field of regulatory science has not received the resources, or the intellectual energy, that it deserves, Hamburg stated in announcing the FDA-NIH collaboration in February. "We have allowed the arm of regulatory science to become weak and under-developed," she said, adding that if this situation is not fixed "we will row in circles."

Discoveries and Investment

Hamburg and others are dismayed that the nation's huge investment in biomedical research, epitomized by decoding the human genome, has not translated into important new treatments. For that to happen, Hamburg stated at a February meeting of the Personalized Medicine Coalition (PMC), biomedical discoveries "must be married to a robust investment in regulatory science." This includes developing new tools and standards to assess medical product safety, effectiveness, potency, quality, and performance. Hamburg is looking for standards for novel cell-based therapies, reagents to test flu vaccine potency, and strategies for screening compounds for serious adverse events, among other advances.

Regulatory science is key to advancing personalized medicine by providing the research community with a better understanding of the genetics of drug metabolism and an idea of which patients may be at risk for adverse effects from a particular drug, Hamburg explained. The discovery of genetic markers, for example, has led to labeling to prevent use of certain colon cancer drugs by patients with the K-RAS mutation, who are unlikely to benefit. And biomarker validation projects have produced new rodent assays that can pick up early signs of kidney toxicity.

Hamburg promises to issue long-awaited draft guidance this year on biomarker qualification and the co-development of drugs and diagnostics. At the same time, the commissioner is seeking agreement across FDA centers about the kind of evidence needed to rely on a test result to shape a drug trial, or product approval and relabeling. Hamburg also plans more guidance on clinical trial design—particularly for smaller trials—and more flexible endpoints for rare disease treatments.

Leverage and Collaboration

Because FDA has very limited resources to expand its scientific capabilities, Hamburg is looking for assistance from other government agencies and from industry. In February, Health and Human Services (HHS) secretary Kathleen Sebelius joined Hamburg and NIH director Francis Collins in announcing a collaborative effort to promote regulatory science and ensure speedier patient access to therapies. The three-year, $6.75 million program is tiny by NIH standards, but won praise as an important first step towards developing new approaches to biomedical product development. NIH and FDA are providing $2 million and $250,000 each year, respectively, which will support two or three annual grants to academic researchers.

Collins and Hamburg will co-chair a Joint Leadership Council composed of leading scientists from both agencies. The council will define the research agenda with help from the broader research community at a public meeting this spring. The panel also will encourage NIH officials to consider regulatory issues in building the institute's research programs, and seek to integrate the latest science into FDA's review process.

Many of these issues were examined at a workshop sponsored by the Institute of Medicine (IOM) Drug Forum in late February. That group has been discussing the need to improve FDA's science base since it issued a 2007 report on drug safety, which highlighted this gap in agency expertise. Hamburg noted that FDA's partnership with NIH might provide a model for similar relationships with other government agencies, such as the National Institute of Science & Technology (NIST) and HHS' Biomedical Advanced Research & Development Authority (BARDA).

Barely Breaking Even

Despite Hamburg's vigorous campaign to strengthen science at FDA, the commissioner has limited resources to carry out her plans. The Obama administration's FDA budget plan for 2011 provides $25 million for an Advancing Regulatory Science initiative—an amount that reflects the overall squeeze on FDA funding for next year. Only by collecting $1.5 billion in user fees does FDA's total budget reach $4 billion, representing the 25 percent increase highlighted by the White House. With just a 6 percent rise in appropriations, FDA barely breaks even, explained consultant Steven Grossman.

Moreover, much of that $25 million is targeted to specific projects, such as improving FDA expertise in nanotechnology and stem cell research, and setting standards for biosimilars. FDA chief scientist Jesse Goodman would have $3 million to oversee research and collaboration. But there's a paltry $4.5 million allocated for FDA's much larger Critical Path Initiative, which has been struggling to support biomarker validation collaborations and to modernize clinical research.

The proposed amount will enable FDA to bring in a handful of scientists to bolster these initiatives, expand staff training, and provide support for research projects. There is talk of forming a network of academic "centers of excellence," and of an independent research entity to help FDA answer tricky questions about product efficacy and safety—but those require much more money to move off the back burner. At the IOM workshop, HHS deputy secretary Bill Corr emphasized the administration's commitment to these efforts, describing the admittedly modest funding of science at FDA as a "foundation for more to come."

However, some policymakers are skeptical that FDA needs more resources to do its job. Rep. Rosa DeLauro (D-CT), chairman of the House Appropriations subcommittee that oversees FDA funding, declared that "FDA has many problems that won't be solved by throwing money at it." DeLauro is unhappy that drug safety issues continue to erupt, and that FDA has trouble implementing programs that are already on the books.

One optimistic note, observed Eli Lilly vice president Gail Cassell, is that other government agencies such as NIH and BARDA are becoming more aware of FDA's importance in developing new therapies and countermeasures against biological threats. Cassell recently chaired another IOM meeting on strategies for developing medical products for public health emergencies, which examined FDA's critical role in facilitating access to such treatments and to products with low commercial viability.

Hamburg acknowledged that current initiatives don't provide enough money to do all that needs to be done, "but it's a start." At a minimum, the commissioner hopes to systematize how the agency addresses regulatory science and expands collaborations with external partners. The larger task of restoring the confidence of policymakers and the American people in FDA requires sustained funding and autonomy to do its work without being "buffeted by outside forces."

But even modest funding for regulatory science will draw the attention of academia, noted New England Journal of Medicine editor Jeffrey Drazen. And, he added, it may help get the politicians off of FDA's back.

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at jwechsler@advanstar.com