Day Two

• Develop antigen-binding assays to verify the structural integrity of bispecific molecules, ensuring both binding arms remain functionally intact, and the product retains its intended activity
• Apply a strategic cell line selection approach for cytotoxicity assays to develop a physiologically relevant bioassay that accurately models the MoA of ADCs
• Optimize and streamline bioassay method transfer from ARD to QC to accelerate implementation while ensuring robustness, reproducibility, and regulatory compliance

• 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

• Design and qualify an early-phase, MoA-relevant cell-based potency assay – capturing target binding, internalization, and payload-driven response.
• Adopt linear regression to model the concentration-response relationship — reducing bias and enabling accurate potency estimates across the working response range.
• Identify and resolve key technical challenges to ensure late-phase readiness for the selected candidate.

Exploring the future of potency, where assays must mimic the tumor microenvironment and measure integrated functions beyond cytotoxicity. This panel will debate the practical limits of complexity, the role of surrogate assays, and how to validate a “systems biology” approach to potency.

Join a strategic discussion on building the agile ADC development organization of the future by:

• Debate how complex a potency assay should become to feasibly develop co-culture assays incorporating immune cells and stromal components to reflect the in vivo mechanism of action
• Explore the potential for non-cell-based binding assays, combined with AI models to serve as validated potency methods, reducing variability and resource strain while linking clinical efficacy
• Define the line between necessary scientific rigor and impractical method proliferation for dual-mechanism ADCs, to understand the minimum number of assays needed to ensure product quality

• Establishing an ADC-specific control strategy framework that addresses critical quality attributes to reduces clinical holds
• Implementing a dynamic, phase-appropriate method and specification roadmap to align analytical rigor with patient risk and accelerating progression through Phases 1 to 3
• Deploying a proactive post-submission readiness plan ensuring a streamlined review and securing timely market authorization for patient access

• Implement a holistic comparability strategy that integrates mass spectrometry-based characterization with forced degradation studies, to move beyond a checklist of attributes and identify critical quality shifts
• Develop a risk-based comparability protocol focused on novel ADC-specific attributes to prioritize patient safety and mechanism of action, for faster regulatory approval
• Structure the comparability report as a compelling scientific story linking analytical data to clinical impact, to transform complex datasets into a clear demonstration of product understanding and control, increasing reviewer confidence