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

• Deconstruct the ADC’s mechanism into discrete steps to identify biologically relevant activity to measure for potency assays, ensuring the method reflects the product’s therapeutic function
• Select or engineer a cell line that accurately expresses the target antigen to create a bioassay that is specific and responsive to the ADC’s activity, enabling reliable potency methods that detect changes in product quality
• Incorporating effector function assays when they are part of the intended MoA to fully capture the multifaceted activity of the ADC, providing a complete picture of potency for molecules designed to engage immune cells

• Implement a single cell-killing assay where the combined effect is the primary driver of efficacy to simplify the control strategy and provide a direct measure of potency, streamlining development and validation for late-stage and commercial control
• Developing two orthogonal assays when it is critical to monitor each payload’s function independently, ensuring consistent quality and function of both therapeutic components
• Use mechanism-specific inhibitors or engineered resistant cell lines in bioassays to determne the contribution payload within a single assay, gaining deep product understanding without the resource burden of developing and validating separate methods

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

• Structure the analytical sections to tell a compelling story of product understanding and control, going beyond simply presenting data to demonstrating a state of control, increasing reviewer confidence and facilitating a smoother BLA approval process
• Choosing characterization and comparability studies essential for submission to avoid unnecessary data while providing critical evidence, enabling a focused and efficient BLA preparation
• Integrate complex data sets for attributes like DAR distribution and impurity fate into a coherent narrative to facilitate regulator assessment of product consistency and control, reducing the risk of major objections and expedite the path to market

• 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

The regulatory landscape for ADCs is at a tipping point, evolving from a “case-by-case” model towards a new paradigm for complex biotherapeutics. This panel will explore how industry leaders can proactively collaborate with global health authorities to shape future guidance, rather than just reacting to it. This discussion will address the most pressing gaps for novel modalities, the role of real-world evidence, and strategies for true global harmonization.

Join us to gain a forward-looking perspective on influencing the next generation of ADC regulation by:

• Defining the critical data needed from industry to justify novel control strategies for bispecific, dual-payload, and high DAR ADCs, moving beyond the small molecule vs. biologic dichotomy to establish a new regulatory framework
• Debating the feasibility of a unified global submission package and identifying the key compromises and scientific principles needed by both industry and regulators to make it a reality
• Exploring how artificial intelligence and advanced data visualization in eCTDs could transform regulatory reviews, enable a more dynamic assessment of complex CMC data and accelerating patient access

• Analyze common “non-hold” comments from recent BLA reviews, to clarify the level of evidence expected by agencies like the FDA at each development stage, enabling sponsors to prepare more targeted and successful submissions from IND to BLA
• Apply a “fit-for-purpose” justification strategy for complex attributes like DAR and impurities, to provide a rationale in the absence of formal ADC-specific guidance, and streamline the approval pathway for novel ADC formats
• Leverage insights from direct regulatory feedback on stage-appropriate characterization to allocate resources more effectively and avoid both under- and over-characterization, therefore accelerating timelines and reducing CMC development costs