FDA Finalizes Cell and Gene Therapy Potency Guidance, Replacing 2011 Document

The US Food and Drug Administration has issued final guidance telling makers of cell and gene therapies how to build potency assurance into a product's development and manufacture, replacing a 2011 guidance on potency testing. The agency announced the guidance on November 2, and the notice of availability appeared in the Federal Register on November 3.

The document, titled "Potency Assurance for Cellular and Gene Therapy Products," finalizes a draft of the same name issued on December 28, 2023.

What the guidance recommends

The Federal Register notice describes a potency assurance strategy as an approach that reduces risks to potency through manufacturing process design, manufacturing process control, material control, in-process testing and potency lot release assays. It says the goal is to ensure that every lot released "will have the specific ability or capacity to achieve the intended therapeutic effect."

The FDA said the recommendations cover every stage from early-phase investigational new drug submissions through biologics license application approval and post-market verification. Key topics include controls for variability in raw materials, testing during manufacturing and lab tests confirming that each batch is biologically active in a way that matches its intended effect. The agency said the guidance also addresses products with short shelf lives, viral vector gene therapies and patient-specific therapies.

According to the notice, changes from the draft include 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 throughout.

The notice cautions that because cell and gene therapy products are diverse and potency assays are product-specific, its recommendations on selecting and designing those assays "are necessarily general."

Expectations by development stage

Regulatory Focus, published by the Regulatory Affairs Professionals Society, reported on the document's details. It said the guidance explains that a biologics license application must demonstrate that a product is safe, pure and potent, and that each lot must be tested for potency with an assay performed after the manufacturing steps that could affect potency are complete, though alternative approaches may be allowed if they provide equal or greater assurance.

The report said the amount of information FDA expects in an investigational application scales with the phase of development. It also said the agency warns it may place a study on hold if an application lacks the potency information needed to assess risk to participants, or, for Phase 2 and 3 studies, if a trial's design falls short of meeting its stated objectives.

The report quoted the guidance as saying product lots planned for Phase 2 or 3 studies "should be sufficiently potent, otherwise the product lots may not have the capacity to achieve the intended therapeutic effect."

Status and next steps

"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, director of the FDA's Center for Biologics Evaluation and Research, said in the agency's announcement.

The notice says the guidance represents the agency's current thinking and is not binding on the FDA or the public, and that an alternative approach may be used if it satisfies applicable statutes and regulations. Comments on agency guidances may be submitted at any time under docket number FDA-2023-D-4299.

The FDA said it will host a webinar on December 10, 2026, on understanding and implementing the guidance.