FDA finalises potency-assurance guidance for cell and gene therapies

The Food and Drug Administration has finalised its guidance on how manufacturers should assure the potency of cell and gene therapies, the engineered biological products that account for a growing share of new approvals. The notice announcing the final guidance, "Potency Assurance for Cellular and Gene Therapy Products," was published in the Federal Register on 3 November 2026 under docket number FDA-2023-D-4299 [s1].

What potency assurance means

Potency is a measure of whether a product can do what it is supposed to do. The FDA's goal, stated in the guidance, is "to ensure that every lot of a product released will have the specific ability or capacity to achieve the intended therapeutic effect" [s1]. For cell and gene therapies — products the agency regulates as biological products under section 351 of the Public Health Service Act — that is harder than for a conventional drug, because the products are living or genetically complex and vary from batch to batch.

The guidance sets out what the agency calls a potency assurance strategy: a multifaceted approach that reduces risks to a product's potency through five elements. These are manufacturing process design, manufacturing process control, material control, in-process testing, and potency lot release assays [s1]. The agency describes the overall approach as grounded in quality risk management [s1]. The framing matters because it shifts the emphasis away from treating a single end-of-line potency assay as the sole guarantee of quality, and toward building potency assurance in across the whole manufacturing process.

Development versus licensure

The guidance treats products differently depending on where they are in their lifecycle. For investigational products — those still in clinical trials — the FDA describes how a developer should progressively implement a potency-assurance strategy during development, and offers additional considerations for products undergoing rapid clinical development [s1]. For licensed products, the document describes the requirements for potency assurance, including the testing required for lot release assays [s1].

The FDA also acknowledges the limits of prescriptive advice here. Because of the diversity of these products and the product-specific nature of potency assays, it writes, its recommendations on the selection and design of potency assays "are necessarily general" [s1]. The guidance emphasises that potency assays and their acceptance criteria should be designed to make meaningful contributions to potency assurance by reducing risks, and it provides illustrative examples of assay-development approaches [s1].

What changed from the draft

This final guidance finalises a draft of the same title that the FDA issued on 28 December 2023 [s1]. The agency says it received several comments on that draft and considered them in finalising the document. The summary of changes it lists includes advice on integrating potency assurance into existing quality systems, expanded risk-assessment guidance, advice on regulatory engagement pathways, and additional practical examples with refined terminology, along with editorial changes to improve clarity [s1].

The status of guidance

It is worth being precise about what a guidance document is. The FDA states that the document is being issued consistent with its good guidance practices regulation and "represents the current thinking of FDA" on the subject [s1]. It "does not establish any rights for any person and is not binding on FDA or the public," and a manufacturer "can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations" [s1]. The guidance itself contains no new collection of information, the agency notes, though it refers to previously approved collections [s1].

That is a different legal weight from a rule. The dialysis and organ-procurement payment changes the FDA's sister agencies issue as rules carry the force of regulation; a guidance signals how the FDA intends to exercise judgement, and comments can be submitted at any time [s1].

What is settled

What is fixed by this action is that a final, dated guidance now exists, replacing the 2023 draft, and that it lays out a five-element, risk-based framework for potency assurance across the product lifecycle [s1]. For developers of cell and gene therapies, the practical significance is that the agency's current expectations — from early development through lot release of a licensed product — are now set out in a single finalised document rather than a draft. The guidance is available through the FDA's biologics guidance pages and on the federal rulemaking portal [s1].