Abstract: Potency is a fundamental critical quality attribute (CQA) and serves as a key measure of product consistency, stability, and biological activity throughout the product lifecycle. Unlike small-molecule drugs, biological products often exhibit complex mechanisms of action and inherent manufacturing variability, creating unique challenges for the development and validation of potency assays. While potency methods are intended to reflect biological activity relevant to clinical performance, many assays measure only selected functional attributes and are not direct surrogates for clinical efficacy. Regulatory agencies expect potency tests to be scientifically justified, mechanism-of-action-based, where feasible, and suitable for their intended use in product characterization, process development, lot release, stability testing, and comparability assessments following manufacturing changes. The selection and design of an appropriate potency strategy requires balancing biological relevance and inherent biological variability with method robustness, precision, accuracy, linearity, and long-term lifecycle management. The potency test must be suitable to support the intended specifications and be stability-indicating to support the product’s shelf life. This presentation will discuss current regulatory expectations for potency assay design, development, and validation, with examples from a variety of biological products, including vaccines and CAR-T cell products. Specific examples for managing the method’s inherent variability, expressing reportable results, and addressing the challenges in demonstrating stability-indicating capability will be discussed. Participants will gain practical insights into designing potency methods that align scientific understanding of product biology with evolving regulatory expectations.

Contributing Authors:
RAJESH GUPTA
Biologics Quality & Regulatory Consultants, LLC, North Potomac, MD, USA