By Turna Ray

Drug/diagnostic co-development is not the ideal scenario presented by the US Food and Drug Administration's 2005 concept paper, which describes regulatory and evidentiary guidelines for the simultaneous development of a single test in conjunction with a single drug, a white paper issued by the Personalized Medicine Coalition this week asserts.

The reality of developing personalized therapeutics — involving a genetic test to determine dosing, predict response, or gauge adverse reactions — is often confounded by varying evidentiary criteria for drugs and diagnostics; differing development timelines for tests and therapeutics; and divergent business motivations of pharmaceutical and diagnostic firms. As a result, PMC argues in its white paper, any forthcoming FDA guidelines on drug/diagnostic co-development must delineate areas of regulatory flexibility and address alternative development models to account for the realities of this strategy.

Rx/Dx co-development is considered the linchpin of personalized medicine. But since issuing a concept paper more than four years ago, the FDA has not put forth more definitive guidance explaining how sponsors should develop combination products or how the agency plans to coordinate its drug and diagnostic divisions to review such products.

Meanwhile, genomic advances have marched on, bringing to market hundreds of new genetic tests and several new genetically targeted drugs. Even the FDA has updated labeling for several drugs to recommend or require genetic testing prior to administration. This rapidly evolving area of pharmacogenomically guided medicine requires the FDA to revisit its now outdated concept paper on Rx/Dx co-development, which is something the agency has realized.

PMC's white paper, written at the suggestion of the FDA, comes at a time when the agency is going back to the drawing board on crafting regulatory policy for genomic medicine. Recognizing that the field of pharmacogenomics has rapidly advanced since 2005, the agency is planning to hold public hearings and issue a series of white papers outlining the most up-to-date knowledge on the issue [see PGx Reporter 04-22-2009].

"The concept paper, as currently drafted, comprehends only a narrow slice of innovative diagnostic development," the PMC noted in the white paper. "Overall, the concept paper implies that the diagnostic and the drug are manufactured either by the same company or by two companies with common interests. This is often not the case.

"Given the different timelines associated with the development of drugs versus diagnostics, many requirements contemplated in the concept paper could add significantly to the time required for commercialization of products (both drugs and diagnostics) and hamper the ability of independent diagnostic companies to innovate," the PMC stated.

In addition to issuing the white paper, PMC has also proposed a list of topics for FDA public workshops or white papers on drug/diagnostic co-development. The topics include: regulatory process for companion diagnostic approval and drug labeling updates; evidence requirements for combination products; pre-clinical pilot feasibility studies; adaptive trial designs; FDA interagency coordination in reviewing drug/diagnostic combination products; as well as issues beyond the stated scope of FDA's concept paper.

Non-Ideal as the Norm

Over the four-year period since FDA first issued its concept paper, the agency has updated several drug labels with genetic information, and a number of drug and diagnostic firms have gained experience with launching combination products. One thing that has become clear is that although FDA might prefer the simultaneous development of a drug/diagnostic product, the reality doesn't always play out in such an idyllic fashion.