The FDA must be “a consistent catalyst for innovation,” insisted FDA commissioner Margaret Hamburg, M.D., in a July 13 letter to colleagues. That determination couldn’t come at a more critical time.
The scientific, logistical, and administrative challenges are significant. “Innovative products that are truly transformative create unique scientific and regulatory challenges,” Dr. Hamburg acknowledged. The food, drug, and cosmetic industries have a global reach and a global supply chain, with international regulatory hurdles. Administratively, the FDA faces the challenges of any large organization—providing the resources and training necessary to keep its staff of 12,000 performing at peak efficiency.
Following the April release of its Strategic Priorities 2011–2015 document, the FDA has released several proposals to streamline drug testing, nanotechnology, and low-risk diagnostics, as well as draft companion diagnostics guidance, in an attempt to increase regulatory uncertainty and the speed and accuracy of reviews.
But, as Dr. Hamburg recently wrote to colleagues, “The most obvious change is that the Agency’s programs will be divided into directorates that reflect the core functions and responsibilities of the Agency.” Her goal is to better support core functions and to link programs that share common regulatory and scientific foundations. The seven existing centers, she emphasized, will remain under their current leadership.
To enhance consistency, the position of Deputy Commissioner for Medical Products and Tobacco is being established to oversee the “Special Medical” programs and to provide “high-level coordination and leadership” across the seven centers. The FDA is also establishing the Directorate of Global Regulatory Operations and Policy, to move the FDA from “an organization regulating domestic products to one overseeing a worldwide enterprise.”
The Office of the Chief Scientist will continue its efforts to “improve FDA’s science and address issues of cross-cutting scientific concern.” The National Center for Toxicological Research will report to this office. The FDA is also forming the Office of Foods to implement the Food Safety Modernization Act, and the Office of Operations to oversee administrative functions, including information technology and finance.
This implementation shares some commonalities with the improvements proposed by BIO CEO Jim Greenwood in his keynote speech at this year’s BIO International convention in Washington, D.C. There, he advocated establishing the FDA as an independent agency, updating its mission statement to create a clear mandate to encourage the development of innovative products, creating a chief innovation officer, and developing a progressive approval pathway.
BIO proposes making the FDA an independent agency, like the Environmental Protection Agency, with a fixed term of office for the commissioner. “That would insulate the agency from being second-guessed by external stakeholders and provide additional ability to advocate for funding through the appropriations process,” explained Andrew Emmett, managing director for science and regulatory affairs, BIO.
Allowing a fixed term for the FDA commissioner would increase the likelihood of continuity within the FDA, Emmett continued. Currently, the FDA commissioner is appointed by the Administration so, electing a U.S. President typically triggers the appointment of a new FDA commissioner and a change in FDA priorities.
A fixed appointment—perhaps six years—would insulate the commissioner to some degree from the political gammoning that plagues the position.
Independence could also improve the FDA’s budgetary situation. Currently, the agency submits its proposed budget to the Department of Health and Human Services, which balances FDA requests against those of its sister organizations, and submits a significantly pared down version to the Congressional Office of Management and Budget (OMB). As a separate agency, however, the FDA would submit its budget request directly to the OMB, thus increasing its chances of obtaining the budget it needs. The National Cancer Institute, although not independent, submits its budget this way now, Emmett added.
The products the FDA regulates represent 20% to 25% of every consumer dollar spent in the U.S., Dr. Hamburg pointed out. “That’s a gigantic percent of the country’s gross domestic product,” Tim Rodell, M.D., CEO of GlobeImmune (www.globeimmune.com) and a member of the BIO board of directors, said. “Given the FDA’s importance, it warrants being a cabinet-level agency.”
In the long term, the main issue is how the FDA can facilitate an influx of novel medicines to significantly improve patient outcomes.
21st Century Medicine
Molecular diagnosis and personalized medicine provide opportunities to bring effective therapeutics to patients sooner by allowing biopharma companies to develop faster, more targeted trials that, consequently, require fewer patients.
“Co-development of diagnostics and therapeutics is an area of great interest and concern,” noted Paul Radensky, M.D., J.D., partner with McDermott Will & Emery. Recognizing that, the FDA released the new draft guidance for in vitro companion diagnostic devices on July 14 to resolve issues between the Clinical Laboratory Improvement Amendments of 1988 process and the FDA’s 2007 Draft Guidance for Industry, Clinical Laboratories, and FDA Staff: In Vitro Diagnostic Multivariate Index Assays.
The draft guidance recognizes the importance of co-development, while providing flexibility to accommodate multiple timelines.
“One of the challenges with regulating in vitro diagnostics as medical devices,” Dr. Radensky said, “is that we’re talking about the accuracy, reliability, and reproducibility of the test with respect to the information furnished by the test.” The Coalition for 21st Century Medicine, a group of laboratories, venture capitalists, and patient groups interested in advanced diagnostics, is examining the issues associated with personalized medicine.
The Coalition is working with Senator Orrin Hatch (R-UT), who is considering options for an oversight framework based upon the potential for inaccurate test results to harm patients.
The application of molecular medicine opens a huge opportunity for companion diagnostics, noted Kevin Hrusovsky, president and CEO of Caliper Life Sciences. “So far, 14 drugs have been approved requiring companion diagnostics, and approximately 56 recommend using molecular diagnostic tests. This is a major technology innovation.
“Unfortunately, many drug companies didn’t start their biomarker work early.” Instead, many waited until their therapeutic entered Phase III trials to begin developing a companion diagnostic program. “They didn’t have a diagnostic infrastructure in place and didn’t understand the challenges of diagnostic approval, so were quite frustrated.”
Moreover, they did not have the benefit of stratification to mitigate clinical risks in terms of safety and efficacy, which led to an unnecessarily high failure rate. “Now, pharmaceutical developers are embracing these opportunities and initiating biomarker/companion diagnostics programs much earlier in the discovery process,” he said.