Greater Clarity on Coverage Urged for Companion Diagnostics Guidance

Draft guidance on companion diagnostics development needs more clarity on what products it covers and greater detail on clinical trial criteria, trade groups said in comments on the draft.

Companion diagnostics are on the rise, the Pharmaceutical Research and Manufacturers of America (PhRMA) observed in its comments to the FDA. Nearly 30 drugs and biologics with an IVD companion diagnostic have been approved as of June of this year, with many more under development by biopharmaceutical companies, wrote Kristin Dolinski, PhRMA’s director for science and regulatory advocacy.

“Therefore, it is critical that both biopharmaceutical and diagnostic sponsors have a clear and predictable pathway for the development and regulatory review of such products,” she indicated.

Geared toward makers of therapeutic drugs and in vitro diagnostics (IVDs) that “codevelop” drugs and accompanying IVDs, the guidance outlines the regulations that govern the development of these products. It also describes what product developers should consider in obtaining marketing authorization and initiating clinical trials, and the administrative issues involved with submitting a codeveloped IVD/therapeutic product.

Detail on Trial Criteria

Several commenters want more information from the FDA on clinical trials, including what criteria should be set for investigational IVD companion diagnostics that are studied in trials of therapeutic drugs.

To assist product sponsors, PhRMA suggested that the FDA in an appendix to its guidance provide instructive examples on setting risk determination criteria. “Since risk determination is evaluated in the context of a specific therapeutic clinical trial design, risk evaluation for an investigational IVD can be somewhat subjective,” Dolinski explained. The appendix could address topics such as using archived versus fresh biopsy material and the types of “invasive” biopsy sampling procedures that pose significant risk, the comment paper suggested.

Although it applauded the FDA’s efforts to allow use of clinical trial assays (CTAs) in early phase clinical trials, executives of the American Association for Cancer Research asked that the FDA “provide further guidance on what standards such CTAs will have to meet for use in allocating patients to therapy in clinical trials.” This is to ensure that the assays used to help manage trial subjects are accurate, they emphasized.

AdvaMed Seeks Clarity on Scope

AdvaMedDx, a division of the Advanced Medical Technology Association (AdvaMed) whose members produce IVD products, asked how the guidance would address follow-on companion diagnostics—those not associated with the original trial. It also suggested that the FDA offer examples of products the guidance would cover.

“In that vein, we suggest the scope of the guidance be more clearly outlined as not to create indiscriminate application to other diagnostic tests. This will avoid confusion among sponsors not otherwise meeting the definition under the guidance,” wrote Khatereh Calleja, AdvaMed’s senior vice president for technology and regulatory affairs, technology and regulatory affairs.

The guidance, for example, could be mistakenly applied to a diagnostic that tracks the efficacy of a therapeutic drug by monitoring blood concentrations of certain chemical substances or analytes, Calleja wrote.

For the most part, AdvaMedDx praised FDA’s effort, claiming it underscores the agency’s expertise in the field of personalized medicine “and is a positive step in supporting innovators who are bringing new safe and effective diagnostic technologies to the U.S. to advance personalized medicine.”

Read the draft guidance here: www.fdanews.com/10-21-16-TherapeuticProduct.pdf. Read the comments on the draft guidance here: https://www.regulations.gov/docketBrowser?rpp=25&so=DESC&sb=commentDueDate&po=0&dct=PS&D=FDA-2016-D-1703. — Jennifer Lubell