FDA 发布 CGT 效价保证策略最终指南

The FDA’s CBER director said patients should have assurance that administered products will work as intended.

Despite moving to loosen certain cell and gene therapy (CGT) quality requirements earlier in the year, the US Food and Drug Administration (FDA) is now tasking manufacturers with placing a higher priority on potency standards through the development lifecycle.

In final guidance for a potency assurance strategy, the FDA wants to ensure that all products “meet a required level of what it is supposed to do therapeutically” before reaching a patient.

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The guidance replaces the FDA’s 2011 potency testing guidance for CGT products and applies to treatments for serious and often life-threatening conditions. By law, manufacturers are expected to verify that their products work as intended, from the time of approval through post-approval monitoring.

The move comes as potency assessment remains a major bottleneck in CGT development, with regulatory scrutiny of inadequate assays delaying the progress of therapies despite promising clinical data.

“Patients who receive CGTs 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,” said Karim Mikhail, director of the Center for Biologics Evaluation and Research (CBER).

“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,” he added.

The FDA has provided manufacturers with recommendations on how to integrate potency considerations throughout a product’s lifecycle – from early-phase investigational new drug (IND) submissions through biologics license application (BLA) approval and continued post-market verification.

Effectively, the framework should ensure that each batch of a CGT is biologically active in a way that matches its intended therapeutic effect. This means checking variability in raw materials, testing during manufacturing, and continued lab tests.

For example, a 2023 study on CAR-T cell therapies found that transduction efficiency varied from 23% to 81% across clinical manufacturing batches. Despite all batches meeting potency criteria, the study’s authors suggested that variability in patient starting material and viral vector batches could have contributed to the large range.

Despite the tightening of potency standards, the FDA increased the flexibility for CGT manufacturers earlier this year. In January, the agency loosened quality requirements as part of efforts to expedite patient access to the therapies. These came under the leadership of former FDA commissioner Marty Makary. It is unclear how the latest guidance interacts with the earlier reforms, though there appears to be regulatory tension between the two.

Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva.

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