BETHESDA, Md. — Guidelines that come out of the US Food and Drug Administration's drug-diagnostic co-development "concept paper," released last week, might eventually aid diagnostic firms and drug developers to more painlessly produce "theranostic" companion products. But as a very preliminary draft, the paper, which can be read here leaves companies in the dark regarding several issues, including the question of how this new process squares with the voluntary genomic data submissions (VGDS) guidance — a "critical issue" in the eyes of one diagnostic giant.
"I think they've worked hard on this," Chris Webster, chair of the genomics group at the Pharmaceutical Research and Manufacturers of America, said at DIA's Pharmacogenomics in Drug Development and Regulatory Decision Making meeting, held here this week. "There are lots of issues that we'd like to see them address — industry always likes to have certainty … they never get certainty. But I think there are some issues here that we've identified, like the role of the VGDS process," he said.
"The question is, as far as using both the drug and the diagnostic together — how would they deal with that?" Webster said. "It hasn't perhaps been explored to the extent that we might like it to be explored — what's going on here and how can it really be used?"
Webster, who is also director of regulatory strategy and intelligence at Millennium Pharmaceuticals, said PhRMA would probably submit consensus comments compiled from among its members "around September."
At the DIA meeting, during two sessions entitled "Issues related to the draft drug-test co-development guidance: next steps," Webster, another industry representative, and four FDA officials presented several concerns noted by industry after a July workshop on co-development. This was followed by a hypothetical co-development case for discussion. The fit of the VGDS process into co-development was briefly considered during the session — it vied for time with other issues and the audience's struggle to digest the newly released document — but it remains murky, and, along with several other concerns, it is not addressed in the concept paper.
In her portion of a DIA session devoted to the concept paper, Lois Hinman, director of regulatory affairs at Hoffman-La Roche, said the interaction of co-development procedures with the VGDS process were among a list of "industry critical issues." She said general concerns included "interaction with the [FDA Interdisciplinary Pharmacogenomics Review Group]" and "timing and strategy in relation to VGDS." And in an outline of session, procedures of sharing information with the FDA, including "transition from the Voluntary Pharmacogenomic Data Submission process," are mentioned as "of particular concern" to drug-test sponsors.
A hypothetical drug-test sponsor company would most likely request dialogue with the IPRG concerning preliminary biomarkers "certainly before the decision was made to enroll patients in a clinical trial — for example before the 2a or 2b — when using the test," said Larry Lesko, director of the FDA Office of Clinical Pharmacology and Biopharmaceutics, in a comment from the audience during the co-development session.
But perhaps the VGDS process will grow seamlessly into the theranostic guidance structure. "The voluntary submissions guidance essentially fit into any point in time during that development process," with the same decision tree as in the pharmacogenomics guidance, said Felix Frueh, director of the IPRG. Frueh said that he had seen versions of the concept paper with the IPRG's role mentioned, but the final version omitted it.
A chart of the co-development process, featured as Figure 2 of the Co-Development Concept Paper, depicts voluntary submissions continuing from the end of basic research into the stage at which a sponsor files for approval — essentially lasting for the whole process.
Along with the MaPP describing the responsibilities of the IPRG, the regulatory process detailed in the concept paper outlines the group's role in drug-test co-development. Part of that role is to provide "consults" on genomic data as part of applications for approval, including those involving co-development projects, Frueh said. "This is really where the rubber meets the road, because that's the area where the co-development is going to be either an IND or an NDA or an IDE or whatever it is between CDER or CDRH, for example," he said. The IPRG lacks decision-making power, he added.
The co-development concept can be seen as an extension of the pharmacogenomics guidance, said Frueh. "'How do you coordinate that co-development? At what stage should you be talking to CDRH? At what stage should you submit an IND? And when do you have to have your validation of clinical usefulness shown?' Put that into the context of the drug and the device," he said. The eventual guidance will help usher sponsors through the field of decisions concerning therapeutic area, device complexity, biomarker quality, and market applicability, he said.
Would the IPRG be interested in looking at biomarker data from device companies? "We'd be very interested in seeing that — seeing proof of the use of the device," said Frueh. "If it's data that's going to be useful in an exploratory setting … absolutely," he said. "As a matter of fact, we've gotten a lot of requests from device companies to come in an present their devices, and we sort of rejected them … because CDER is not the place to do that — 'Why don't you generate data with your device and come back to us?' It might be interesting to look at these data sets as a [VGDS]," he said.