Potency assays are an integral part of the overall control strategy and should be designed for each product to measure its specific ability or capacity to effect a given result. The activity measured should represent the intended clinical mechanism of action (MOA) of the product, which can present with unique development challenges for products with multiple active modalities, or for novel product platforms intended for multiple individual or combined targets. These types of products generally function by binding to two or more soluble (e.g., cytokines) or surface-associated target antigens found on different cells (e.g., bridging of two different cells to mediate a response) or on the same cell type. The complexity of MOA(s) create unique development considerations, such as limited ability to leverage prior knowledge, greater reliance on product characterization studies to build product understanding over time (e.g., structure-function studies), and development of new analytical tools capable of predicting whether biologically relevant responses are elicited. This can be a challenge for implementing potency assays that not only reflect the MOA(s), but that are also capable of supporting the control strategy (e.g., detecting changes in relevant CQAs), and are suitable for routine testing in the QC laboratory environment. Challenges in assay development can include, understanding the binding affinity of each modality and overall avidity, the need for multiple targets to be engaged simultaneously to have the intended biological outcome, the possibility for additive or synergistic effects and need for one or more assays to provide a meaningful assessment of the intended clinical response. Therefore, the potency assays for these types of products are more likely to evolve during clinical development as additional product understanding is gained. These unique considerations for development and implementation of potency assays for these novel products will be covered in this session from both the industry and regulator perspectives.
Session Speakers: 13:30 - 13:55 Expectations on Potency Assays for Antibody-based Novel Modalities – A Regulatory Perspective Nailing Zhang, CDER. FDA 13:55 - 14:20 Cell-based Potency Assay: Design and Considerations Janani Kumar, Molecular Templates 14:20 - 14:45 A Potent Solution to a Low Affinity Problem: Potency Release Methods for an NK Cell Targeted Cytokine Morgan Wilson, InhibRx, Inc. 14:45 - 15:10 A High-Throughput Cell-Based Assay for Measuring mRNA-LNP Vaccine Product Potency Nicole Smiddy, Merck & Co., Inc.