FDA draft guidance aims to improve CGT manufacturing

The US Food and Drug Administration (FDA) has published its draft recommendations for managing cell and gene therapy (CGT) manufacturing changes.

The new draft recommendations outline actions for sponsors of Investigational New Drug Applications (INDs) and applicants of Biologics License Applications (BLAs) for CGT products.

The draft guidance covers the FDA’s thinking on the management of manufacturing changes for CGT products and compatibility studies to assess final product quality. This advice will “improve product quality, expand product supply, or improve manufacturing efficiency”, says the FDA.

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Currently, CGT products are assessed under the same regulatory framework as biological products. This poses challenges as the manufacturing of CGT products is generally more complicated and often requires manufacturing changes.

Manufacturing changes “can fundamentally alter the design or nature of the product,” says the FDA, therefore, the new recommendations will help prevent problems down the line, for instance CGT products being out-of-specification (OOS).

The guidance advises to plan risk assessment strategies to evaluate the risk caused by each manufacturing change. Comparability studies should then be performed to assess the impact of the change, either through analytical methods or additional clinical studies.

All manufacturing changes should be reported to the FDA through altering an existing IND. Any manufacturing changes that alter the final product fundamentally should have a separate IND submitted to the FDA.

The FDA concludes, “we recommend that sponsors and applicants of CGT products prospectively discuss proposed significant manufacturing changes with FDA’s Centre for Biologics Evaluation and Research (CBER), particularly when such manufacturing changes would be implemented during later stages of the product lifecycle.”