FDA issues final potency assurance guidance for cell and gene therapies

The U.S. FDA has issued final guidance outlining a science- and risk-based approach to potency assurance for cell and gene therapy products, recommending that manufacturers integrate potency controls throughout product development, manufacturing and postapproval monitoring.

The guidance, Potency Assurance for Cellular and Gene Therapy Products, issued November 2, replaces the agency’s 2011 guidance on potency testing and finalizes a draft released in December 2023. It provides recommendations for developing a comprehensive potency assurance strategy to help ensure that every released product lot has the biological activity needed to achieve its intended therapeutic effect.

The strategy takes a broader approach than relying on a single potency assay, incorporating manufacturing process design and controls, raw material controls, in-process testing and potency assays used for lot release. The FDA emphasizes that manufacturers should use quality risk management principles to identify factors that could affect potency and establish controls appropriate to the product and its stage of development.

The recommendations address the full product lifecycle, from early-phase IND submissions through BLA approval and continued postmarket verification. The level of potency assurance should evolve as manufacturers gain a better understanding of their products and manufacturing processes.

The guidance also addresses challenges specific to CGT manufacturing, including variability in raw materials, products with short shelf lives, viral vector-based gene therapies and patient-specific treatments. For example, manufacturers of individualized therapies should account for variability in patient-derived starting materials when developing potency assurance strategies.

The FDA said the final guidance incorporates additional recommendations on integrating potency assurance into existing quality systems, conducting risk assessments and engaging with regulators. It also includes expanded practical examples and refined terminology compared with the 2023 draft.

“By giving manufacturers a clear, predictable roadmap, this guidance supports faster access to safe and effective therapies for patients who often have no other treatment options,” the agency said in its announcement.

CBER will host a virtual webinar on December 10, 2026, to discuss the guidance and help manufacturers understand its recommendations.