Roles of Bioassay Subject Matter Experts in Developing Potency Methods and Managing Chemistry, Manufacturing, and Controls Deliverables

Abstract Bioassay subject matter experts (SMEs) play an increasingly important role in chemistry, manufacturing, and controls (CM&C) organizations as biologic therapeutics become more complex. This review describes how bioassay SMEs support potency method development and CM&C deliverables from early discovery through commercialization. As therapeutic modalities progress, bioassay control strategies have become more sophisticated, evolving from using simple binding assays to multi-attribute, orthogonal testing approaches. The review summarizes the SME’s expanding contributions to assay design, optimization, method transfer, phase-appropriate qualification and validation, lot release, stability testing, comparability, and regulatory submissions. A case study on ADC potency assay cell-line selection illustrates how biochemical and biological factors affect assay specificity and impurity discrimination. The review also addresses key scientific, technical, and cross-functional challenges, including assay variability and the need for effective leadership across analytical, regulatory, and quality functions. As biologic modalities continue to diversify, interdisciplinary bioassay SME training will be critical to support regulatory-compliant potency strategies.