Validating Bioanalytical Methods for Biomarker Quantitation: A Regulatory Document Review

INTRODUCTION. Biomarkers are used to assess normal physiological processes in the body; to diagnose and select therapy for various diseases; and to develop new drugs. The increasing use of biomarkers as drug development tools necessitates improvements in analytical quantification methods. AIM. This study aimed to review and summarise data on validation of bioanalytical methods for biomarker quantification. DISCUSSION. The analysed regulatory documents were issued by International Council for Harmonisation (ICH), as well as Food and Drug Administration (FDA), including the Biomarker Assay Collaborative Evidential Considerations Writing Group and Critical Path Institute (C-Path); European Medical Agency (EMA); Eurasian Economic Commission (EEC); and other publicly available research platforms (including PubMed, Web of Science, RSCI (eLIBRARY.RU), and Google Scholar online databases) primarily published in 2014–2024. Analytical and clinical biomarker validation was examined, alongside with analytical validation stages and key validation parameters of the bioanalytical method depending on the objective (analysis for pharmacokinetics, bioequivalence, and toxicokinetics studies; biomarker analysis in drug development and for diagnosis in preclinical and clinical studies). Proposed is an algorithm for choosing biomarker analytical validation level depending on the method (chromatography, ligand-binding methods using reagent kits for various purposes) and the issues to be addressed. CONCLUSIONS. Confirming biomarker method suitability as per the objectives is similar to a common validation procedure of bioanalytical methods. A broad and detailed scientific discussion of biomarker analysis validation is needed, since a comprehensive scheme developed for this complex procedure will contribute to more reliable use of biomarkers, improved quality of studies within this process, and resulting safe and effective new medicinal products.