The 2018 FDA Guidance on Bioanalytical Methods Validation (BMV) included biomarker assay validation, the focus was on understanding the challenges posed in validating biomarker assays and the importance of having reliable biomarker assays when used for regulatory submissions, rather than definition of the appropriate experiments to be performed. Different from PK bioanalysis, analysis of biomarkers can be challenging due a number of factors including the presence of target analyte(s) in the control matrices used for calibrator and quality control (QC) sample preparation and greater difficulty in procuring appropriate reference standards representative of the endogenous molecule. The situational nature of biomarker applications results in the need for fit-for-purpose (FFP) validation including method validation requirements be consistent with the proposed context-of-use (COU) for any given biomarker. This presentation will provides specific recommendations for BAV by LC-MS, for both small and large molecule biomarkers from an AAPS Bioanalytical Community working group white paper. The consensus recommendations include: creation of a validation plan that contains definition of the context of use of the assay, use of the PK assay validation elements that support the COU and their acceptance criteria, and definition of assay validation elements adapted to fit biomarker assays and their acceptance criteria.
Learning Objectives:
Understand the need to customize biomarker assays and their validations based on the biomarkers use in developing a therapy for a particular disease (the context of use).
Understand the differences required for validating a biomarker vs drug assay by LC-MS.
Implement best practices for specific experiments required to validate a biomarker assay.
