The FDA’s draft guidance introduces the Potency Assurance Strategy (PAS), a significant shift from focusing on a single potency test to a holistic, risk-based framework for cellular and gene therapy products.
Key Concepts:
- Core Philosophy: The PAS treats potency like sterility—it’s an attribute built into the entire product lifecycle through process design and control. The final potency assay serves to confirm the strategy worked, not to create the potency itself.
- The Process: Developers must identify potency-related Critical Quality Attributes (CQAs), assess risks to them (from manufacturing to administration), and mitigate those risks. The cornerstone of mitigation is a well-designed and controlled manufacturing process, not just the final test.
- Role of Assays: Potency assays are a necessary component used to confirm that CQAs are met. However, they are only one part of the strategy, and the framework allows flexibility—stronger process controls can compensate for limitations in available assays.
- Lifecycle Approach & Consequences: The PAS must evolve, with expectations for rigor increasing from early to late-stage development. An inadequate PAS can lead to a clinical hold, particularly in pivotal studies where it might compromise the study’s integrity or when it poses a significant risk to patients.
