Recent Progress in Biomarker Bioanalysis and Target Engagement Assessment

Abstract

Biomarkers include a diverse array of modalities, from blood chemicals, nucleotides, and proteins to functional imaging. As such, biomarker bioanalysis leverages a variety of technical platforms to meet the analytical needs in drug development. The “fit-for-purpose” assay validation principle has provided a unifying approach for validating biomarker assays on different technical platforms and for different context of use. This chapter reviews recent progress in biomarker bioanalysis with a focus on emerging consensus addressing unique challenges in biomarker assay validation, and their application in the development of quantitative target biomarker assays using ligand binding assay, liquid chromatography-mass spectrometry, and flow cytometry. It provides examples on how knowledge of target levels can inform decisions during clinical drug development. Calibrator material is of paramount importance for assay quality. Target levels and target engagement assessment provide important information for understanding the pharmacokinetics-pharmacodynamics relationship and dose selection.