FDA GUIDANCE DOCUMENT: Potency Assurance for Cellular and Gene Therapy Products

FDA’s current thinking and is not yet final document issued in December 2023, modernizes the regulatory approach for ensuring the potency of cell and gene therapy (CGT) products. It introduces the Potency Assurance Strategy (PAS), a comprehensive, lifecycle-based approach grounded in quality risk management. This strategy shifts the focus from reliance on a single final potency test to a holistic system where potency is proactively built into the product through manufacturing process design, process controls, material controls, and in-process testing.

This draft guidance for cellular and gene therapy products, which will replace the 2011 version, introduces the Potency Assurance Strategy (PAS).

The PAS is a comprehensive, risk-based strategy to ensure each product lot achieves its intended therapeutic effect. It emphasizes a well-controlled manufacturing process to manage risks to potency-related Critical Quality Attributes (CQAs) throughout the product's lifecycle.

While a key component, the potency assay is just one part of the PAS, FDA still requires scientifically justified potency assays, even if their limitations are supplemented by process- and material-controls. Its role is to confirm that CQAs are met, serving as a meaningful indicator of potency without necessarily replicating the product's full mechanism of action. The PAS must be progressively implemented with increasing rigor as a product advances; at IND submission or during ongoing development, inadequate assurance can trigger a clinical hold.