Implementing a tiered approach to bioanalytical method validation for large-molecule ligand-binding assay methods in pharmacokinetic assessments

Abstract Bioanalytical methods must enable the delivery of data that meet sound, scientifically justified, fit-for-purpose criteria. At early phases of biotherapeutic drug development, suitable criteria of a ligand-binding assay could be met for pharmacokinetic (PK) in-study sample testing without a full validation defined by regulatory guidelines. To ensure fit-for-purpose methods support PK testing through all phases of biotherapeutic development, three tiers of method validation – regulatory, scientific and research validations – are proposed. The three-tiered framework for method validation outlines the differences in the parameters that should be assessed, the acceptance criteria that may be applied, and the documentation necessary...