Personalized Medicine Will Require Greater CDER, CDRH Cooperation

Drug regulation during an era of personalized medicine will require cultural if not structural changes on the part of FDA.

The agency's current structure of discrete review centers impedes a unified regulatory approach to the emerging treatment paradigm, C-Path Institute President Raymond Woosley said at the Personalized Medicine Coalition's conference on personalized and evidence-based care Sept. 19.

"If you look at the FDA, they started regulating food - they added a door for drugs, they added a door for diagnostics, they added a door for devices and ... they are very different cultures, they have different languages, they have different approval paths. People in CDER don't know what a 510(k) is, people in diagnostics don't really understand what a supplemental NDA is," Woosley said.

Combining drugs and diagnostics is a central part of personalized medicine. As more information about drug effects on patient subpopulations becomes available, drug utilization will increasingly be linked with diagnostic tools that can identify patients or optimize therapy.

"More and more of personalized medicine will be focused on diagnostics. That will be the means by which we can trigger this customization," Department of Health and Human Services Secretary Michael Leavitt said at the meeting.

HHS has made effectuating personalized medicine a department priority, and FDA seems prepared to take steps in that direction. Commissioner Andrew von Eschenbach has said that the FDA of the future should approve solutions to medical problems and not simply medical products.

FDA is working to establish a regulatory approach to manage the expected influx of drug applications with associated diagnostics. The agency issued a concept paper on drug-diagnostic co-development in 2005 and is expected to release a draft guidance on the topic this year (¹ , p. 29).

A successful step FDA has taken was the creation of the Office of Combination Products in 2002. The office serves to coordinate products that include a combination of drugs, biologics and devices - however, regulatory review and oversight of combination products is still assigned to one of the centers.

The personalized medicine approach of drugs and companion diagnostics will require greater coordination between the Center for Drug Evaluation and Research and the Center for Devices and Radiological Health. Thus far, there has not been a great deal of precedent, as most diagnostics are developed separately after the drug is marketed.

Harmonizing FDA's review centers is not "going to be simple, and ... it is going to take some bending, but not dilution of the environment - we don't want to take short cuts," Woosley said. "We want to ... change the barriers that have been there to innovation."

In its first report on personalized health care, released Sept. 18, HHS indicated that the advancement of personalized medicine may require more than greater inter-center and possibly inter-agency cooperation and that structural changes to FDA may be necessary.

In order to ensure development of clinically useful products, "appropriate regulatory structures will be needed to support innovation and adoption of safe and effective drugs, diagnostics and procedures," the report states.

An example of how creating a dedicated group to concentrate on a policy topic and springboard rhetoric toward real accomplishment is FDA's Office of Translational Science, which was created to oversee the agency's Critical Path Initiative. Prior to setting up the separate office, FDA officials used to comment that working on the Critical Path was a "night job" at the agency - but with a staff and resources, significant progress has been made (² (Also see "“Critical Path” Is On The Road Forward; FDA Reports Industry Activity Is High" - Pink Sheet, 22 Jan, 2007.), p. 29).

Greater organization and dedicated resources could also help personalized medicine gain traction. Before companies will fully buy into the personalized medicine concept, FDA needs to provide industry with a clear regulatory approach to targeted therapies, Avalere Health President Dan Mendelson suggested. "The more clarity there is as to where the policy changes are going the easier it is for companies to make good decisions about what to develop and how."

- Brian Marson ([email protected])