Approval of novel biomarkers: FDA's perspective and major requests.

FDA has been regulating diagnostic tests (including biomarkers) since passage of the Medical Device Amendments of 1976. Although always of interest as diagnostic tools, biomarkers (particularly genetic/genomic) have become of increased interest because of their potential impact on the development and personalized use of drugs. Unfortunately, there seem to be uncertainties among translational researchers as to the specific analytical and clinical measurement criteria needed for the approval of these novel biomarkers. This meeting presentation describes the current FDA perspective and major requirements and data for the validation/approval of an in vitro diagnostic device (IVD) based on a biomarker. The approval process for an IVD based on a biomarker used in the identification of a disease or condition (diagnosing, screening, monitoring) is well established, and is essentially identical to the process to generate sufficient analytical and clinical data for the approval of regular diagnostic devices. On the contrary, approvals for IVDs based on biomarker which may be designed to evaluate the efficacy or answer safety questions for new drug entities are less streamlined. The clinical studies are more complex, resulting in higher ethical standards, increased costs and requiring complex statistical evaluation. There is a small but growing literature on new models for co-development of drugs and diagnostics which will be discussed. Regulators like the FDA develop and bring a flexible regulatory toolbox to the table and are committed to assuring that scientific and regulatory thresholds are tempered to assure rapid access to new technologies while protecting public health.