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FDA Chief Commits to Completing Rx/Dx Codevelopment Guidance This Year, Improving Regulatory Science

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By Turna Ray

At a luncheon hosted by the Personalized Medicine Coalition last week, FDA Commissioner Margaret Hamburg committed the agency to completing its long-awaited drug/diagnostic codevelopment guidance by year end.

“We expect to have this guidance finished by the end of the year," Hamburg told attendees at the PMC luncheon in Washington, DC.

The idea of a forthcoming Rx/Dx codevelopment guidance was floated in a 2005 white paper, which industry observers criticized as too idealistic and out of step with the challenges of managing competing interests and aligning divergent drug and diagnostics development timelines.

The agency last year said it would go back to the drawing board on promulgating guidelines for drug/diagnostic codevelopment by holding public hearings and issuing a series of white papers. In an effort to help the agency in this process, the PMC in December issued its own white paper, after garnering input from 40 of its members, recommending the FDA embrace regulatory flexibility and propose alternative clinical trial models to accommodate a variety of co-development scenarios [see PGx Reporter 12-16-2009].

Expanding FDA's regulatory and scientific expertise to meet changing drug development paradigms in the genomic age has been a common mantra in Hamburg's public speeches of late. So it wasn't a surprise when the day before the PMC luncheon, the FDA and the National Institutes of Health announced they would work together to speed "translational science" into marketed products and improve "regulatory science" at the FDA to usher innovative treatments through the agency.

The FDA defines "regulatory science" as the "development and use of new tools, standards and approaches to more efficiently develop products and to more effectively evaluate product safety, efficacy and quality." A Joint Leadership Council will lead collaboration efforts between NIH and FDA. In addition, the two agencies have issued a request for applications for $6.75 million in grants over three years for regulatory science studies.

"The research supported through this initiative should add to the scientific knowledge base by providing new methods, models or technologies that will inform the scientific and regulatory community about better approaches to evaluating safety and efficacy in medical product development," the agencies said in a statement.

In the realm of personalized medicine, the Rx/Dx codevelopment guidance stands to be among the most significant regulatory science initiatives that could help spur the field. "As commissioner, it is clear to me that we need to develop a consistent, comprehensive and integrated approach to the evaluation and regulation of medical products, which separately, and in combination, comprise the practice of personalized medicine," Hamburg said in a speech last year to the American Association for the Advancement of Science.

"We know for developers to make a substantial investment in this still-evolving arena, they need clear guidelines setting out our expectations and approval standards," Hamburg acknowledged at the time.

Beyond the Rx/Dx codevelopment guidance and the partnership with NIH, another regulatory science improvement underway at the FDA that is likely to impact personalized medicine is the closer alignment of the agency's drug and diagnostics divisions. Efforts have been made to increase the exchange of regulatory and scientific expertise between FDA's Centers for Drug Evaluation and Research, Center for Biologics Evaluation and Research, and Center for Devices and Radiological Health.

Last June, the FDA set up a new personalized medicine group within CDRH's Office of In Vitro Diagnostics Device Evaluation & Safety. The group is tasked with improving the division's knowledge of genomic devices, pharmacogenomics, and proteomics, as well as introducing new approaches for validating complex devices.

Elizabeth Mansfield, the newly appointed director of personalized medicine at OIVD, said at a recent conference that FDA's device division is still working on a regulatory guidance for a complex subset of lab-developed tests, called in vitro diagnostic multivariate index assays [see PGx Reporter 01-20-2010].

Other regulatory science-type initiatives in the area of personalized medicine at the agency include a forthcoming guidance on the validation and use of genomic biomarkers in clinical trials. This guidance is expected to provide industry with a clearer picture of FDA's criteria for evaluating the usefulness of biomarkers in clinical trials.
FDA is "working internally to make sure we have a common understanding across all centers and throughout the agency about the kind of evidence needed when a test result is being used to shape a drug trial, or drug approval or relabeling," Hamburg said at the PMC luncheon.

The industry has asked FDA to further clarify when the agency will accept retrospective biomarker analysis in pharmacogenomic drug trials. In updating labeling for two colorectal cancer drugs, Vectibix and Erbitux, with genomic risk data, the FDA did accept retrospective pharmacogenomic analysis. The circumstances under which FDA accepted retrospective data could serve as a model for sponsors looking to develop companion tests for drugs already out on the market, particularly when prospective randomized controlled trials are not possible or unethical to conduct [see PGx Reporter 10-07-2009].

In this vein, on March 17, the FDA's Pharmaceutical Science and Clinical Pharmacology Advisory Committee will meet in Atlanta, Ga., to discuss scientific issues related to the application of pharmacogenomics in early-stage drug development.

Further clarity on how FDA/NIH's collaboration might spur personalized medicine may be provided at a public meeting the two agencies plan to hold in the spring. A date has yet to be set for this meeting.

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