FDA Finalizes Potency Guidance for Cell and Gene Therapy Products

The FDA has issued final guidance outlining a comprehensive, science- and risk-based approach to assuring the potency of cellular and gene therapy (CGT) products, emphasizing the importance of integrating quality controls throughout product development, manufacturing, and postapproval monitoring.^1,2

Released November 2, 2026, the guidance, Potency Assurance for Cellular and Gene Therapy Products, replaces the agency's 2011 guidance on potency testing. It provides recommendations for manufacturers developing strategies to ensure that each product lot retains the ability to achieve its intended therapeutic effect, addressing manufacturing process design, material controls, in-process testing, and potency assays used for lot release.

The guidance applies to CGT products regulated as biological products under section 351 of the Public Health Service Act, including cellular therapies and tissue-engineered medical products. It does not apply to vaccines for infectious disease indications, bacteriophage products, live biotherapeutic products, fecal microbiota for transplantation products, or allergenic products.

"Patients who receive cellular and gene therapies are often battling serious or life-threatening conditions, such as cancers and rare diseases, and they deserve the assurance that the product administered to them will perform as intended," Karim Mikhail, MS, director of the Center for Biologics Evaluation and Research, stated in a news release. "This guidance reflects the FDA's commitment to ensuring America remains the best place in the world to innovate — and that innovation is matched by the highest standards of product quality and patient safety."

Comprehensive Potency Assurance Strategy

A product’s potency can be affected by factors ranging from its mechanism of action to variability in starting materials and manufacturing processes. Manufacturers should assess these risks by considering the product’s intended therapeutic effect, potency-related critical quality attributes (CQAs), and critical process parameters.

Rather than relying on a single release test, a Potency Assurance Strategy should combine controls appropriate to the product and its stage of development. These may include process design and qualification, material specifications, in-process testing, and potency assays.

For cell-based products, relevant attributes may include cell viability, growth, and phenotype. Manufacturers of autologous therapies should also account for variability in patient starting material, including potential effects of underlying disease and prior treatment.

Potency Testing and Assay Development

Selecting appropriate assays is central to determining whether a product consistently retains its intended biological activity. A combination of physicochemical and biological assays may be appropriate; separate bioassays for every biological activity are not necessarily needed if the overall testing strategy adequately addresses risk. The guidance also encourages in vitro bioassays over animal testing when feasible.

For certain higher-risk clinical investigations, or studies intended to provide substantial evidence for a marketing application, the strategy should include at least 1 qualified physicochemical assay or bioassay for lot release that quantifies a potency-related CQA. Release and in-process assays should be validated before a biologics license application.

For products with very short shelf lives, completing a bioassay before administration may not be feasible. Manufacturers may instead use physicochemical release assays and in-process testing, with bioassays initiated after manufacture and evaluated after release.

For gene therapies using viral vectors administered directly to patients, early release testing generally should measure transgene messenger RNA or protein expression, or protein activity, in transduced cells. For patient-specific, vector-transduced cell products, each vector lot's biological activity should be assessed before use, in addition to testing the final product.

Applying the Strategy Throughout Development

The level of potency assurance should evolve as manufacturers gain a better understanding of the product and its manufacturing process. Release assays should have quantitative acceptance criteria, including a lower limit to ensure adequate potency and, when relevant, an upper limit to address potential safety concerns from excessive potency. For licensed products, criteria should be linked to clinical lots shown to be effective.

Early engagement with the FDA's Center for Biologics Evaluation and Research may help manufacturers address questions about their strategies, particularly when considering changes for higher-risk products. The agency will host a webinar on the guidance on December 10, 2026.

REFERENCES

1. Potency Assurance for Cellular and Gene Therapy Products: Guidance for Industry. US Food and Drug Administration. November 2026. Accessed November 3, 2026. https://tinyurl.com/2yt2m73w

2. FDA Provides Clarity to Support Cell and Gene Therapy Development and Quality. News release. US Food and Drug Administration. November 2, 2026. Accessed November 3, 2026. https://tinyurl.com/4w4cu9js