FDA Finalizes Potency Assurance Guidance for Cell and Gene Therapies: What Changes
On November 2, 2026, the FDA's Center for Biologics Evaluation and Research (CBER) issued final guidance titled "Potency Assurance for Cellular and Gene Therapy Products." It replaces the agency's January 2011 guidance on potency tests and finalizes a draft first released in December 2023, RAPS reported.
Potency is a product's specific ability to produce its intended effect. For a gene therapy, that might mean how well a vector makes its protein inside cells. For a CAR-T product, it might mean how well the cells kill their target. Every lot a patient receives has to work as intended, and proving that has been one of the hardest manufacturing problems in the field.
From one test to a strategy
The biggest shift is conceptual. Instead of relying on a single release test, the FDA wants developers to build a potency assurance strategy: "a comprehensive approach to help ensure that every lot of a product will have the specific ability" to achieve its intended effect. That strategy combines process design, material controls, in-process testing and potency assays, guided by a risk-based understanding of the product and its mechanism of action.
Key recommendations
Phase-appropriate expectations: potency information should scale with development, from early INDs through licensure and post-market verification.
Lot release: for studies meant to support approval, at least one qualified assay that measures a potency-related quality attribute, with release and in-process assays validated before a BLA.
Mixed methods: a combination of physicochemical and biological assays may be appropriate. A separate bioassay for every biological activity is not necessarily required, and in vitro assays are preferred over animal testing when feasible.
Viral vectors: early release testing generally should measure transgene mRNA or protein expression, or protein activity, in transduced cells.
Short shelf-life products: physicochemical and in-process testing can support release, with bioassays started after manufacture and evaluated after release.
Missing potency information can be grounds for a clinical hold on an IND.
Sources: Targeted Oncology and RAPS.
What changed from the 2023 draft
The risk-based lifecycle framework is the same. The final version adds advice on fitting potency work into existing quality systems, more detail on risk assessments, recommendations for engaging with regulators early, new examples and refined terminology. According to DLA Piper, it also adds a mention of new approach methodologies (NAMs) and computational methods, and endorses pre-IND and other formal meetings.
Why it matters
Cell and gene therapies are often made in small batches, sometimes one patient at a time, and their biology is complex. Clear potency expectations help developers plan earlier and can reduce late surprises during review. CBER Director Karim Mikhail said patients receiving these therapies "deserve the assurance that the product administered to them will perform as intended," BioPharm International reported.
The FDA will hold a webinar on the guidance on December 10, 2026.
New to how cell and gene therapies are made and tested? The Life-Changing Power of Gene Therapy (affiliate link) covers the basics.
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