The attention to biomarkers in the Draft Guidance reflects the importance attributed to them in the FDA’s Critical Path Initiative (see GEN, FDA News & Analysis, January 15, 2005).
In the context of that Initiative, the Agency anticipates that today’s biomarkers will become tomorrow’s diagnostics, and continued progress in biomarker development will have wide applicability from in vitro diagnostics to therapeutic monitoring and assessment.
The recent market clearance issued by the Center for Devices and Radiological Health (CDRH) for the first DNA microarray diagnostic test (the Affymetrix GCS 3000Dx system for analyzing the genes from the cytochrome p450 family) is a case in point.
A set of charts are appended to the Draft Guidance to help sponsors understand when or whether pharmacogenomic data should be submitted, with the variables being the nature of the filing, the sponsor’s intentions regarding the data, and the classification of the data as a known or probable valid biomarker.
While it may be that the present experimental nature of most pharmacogenomic data will make it unreliable for regulatory decision making, the authors of the Draft Guidance clearly hope that the framework they have articulated for characterizing that data in that context will encourage sponsors to submit such data where they would not have in the past.
Such voluntary submissions, when aggregated under the auspices of the IPRG, could help establish future known valid biomarkers that will move the field of pharmacogenomics closer to its promise of individualized therapy.
Several pharmaceutical and biotechnology companies have submitted written comments to the Draft Guidance docket. Many of these comments offer extensive evaluations of the document while a number of others offer specific changes to be made to the text.
Although the commentators are almost uniformly supportive of the Agency’s interest in expanding the use of pharmacogenomic data in its regulatory decision making, many raised a number of questions regarding the document’s apparent interposition of a sponsor’s “decision making” with its “regulatory decision making” for purposes of identifying required submissions as well as the process for and subsequent treatment of voluntary submissions.
Several comments noted that pharmacogenomic data may be used through the discovery process to prioritize drug candidates without subsequently serving to address questions of safety or efficacy during the development testing of specific candidates.