Why is Biomarker Assay Validation Different from that of Pharmacokinetic Assays?

The Food and Drug Administration (FDA) issued a long awaited guidance document on Bioanalytical Method Validation for Biomarkers (BMVB) (1) in January 2025, which replaces the 2018 FDA guidance on Bioanalytical Method Validation (BMV) (2). Since then, the AAPS Biomarkers and Precision Medicine Community Leadership Team has held community-wide discussions on the interpretation of this new guidance and its impact on practical approaches involved in biomarker method validation. The 2025 FDA BMVB guidance recognizes that analytical validation of assays that measure biomarkers differs from the validation of assays that measure drug concentrations, and states “a fit-for-purpose (3) approach should be used when determining the appropriate extent of method validation.” However, the 2025 FDA BMVB redirects to ICH M10 (4), which was established for pharmacokinetic (PK) method validation, as the starting point for the analytical validation of biomarker assays. At the same time, it acknowledges that many aspects of ICH M10 cannot be directly applied to various bioanalytical platforms used to measure biomarkers, and different characteristics should be considered, justified, and reported accordingly.