Designing Potency Assays to Demystify the Mechanism of Action to reflect multiple Bioactivities of the Molecule
- Health Authority expectations include defining the primary, payload-mediated MoA and characterization of secondary MoAs (e.g., ADCC, ADCP, CDC) based on IgG subclass/engineering, target biology, and potential impact on efficacy and safety
- Fc effector functions as secondary MoA in ADC molecules can be demonstrated in vitro via ADCC, ADCP, and CDC assays. Fc determinants like glycosylation and Fc engineering should be monitored across Process lots and batches
- In vitro evidence of effector activity does not always translate to in vivo relevance; carefully designed in vivo studies with appropriate controls are often needed to confirm and finalize the MoA