FDA details CMC flexibilities for cell and gene therapy BLAs

Lieutenant Commander Jessica Dunn, associate director in the Center for Biologics Evaluation and Research’s Office of Compliance and Biologics Quality, and Dr. Kimberly Schultz, director of Division 2 in CBER’s Office of Gene Therapy in the Office of Therapeutic Products, presented a webinar explaining a May 2026 FDA guidance that consolidates CMC flexibilities for human cellular and gene therapy products being developed for Biologics License Applications (BLAs).

The guidance groups possible regulatory judgment in four categories: flexibilities during clinical development, process‑validation flexibilities, commercial‑specification flexibilities, and additional flexibilities such as stability and alternative analytical approaches. "In this presentation, we will walk you through how FDA applies regulatory judgment to CMC requirements," Dunn said, describing the consolidation as intended to promote consistent application and expedite development and patient access.

Schultz emphasized a life‑cycle approach to product development. She noted that early‑phase clinical studies that focus on safety may be subject to different current good manufacturing practice expectations than later phases and advised sponsors to set acceptance criteria that focus on safety in early trials and to establish predefined acceptance criteria before phase‑2 studies. "We recommend that you discuss plans with your review team to establish acceptance criteria to support interpretation of clinical efficacy studies," Schultz said.

On process validation, Schultz said FDA does not specify a minimum number of process performance qualification (PPQ) batches and will consider context‑specific factors such as product complexity and the level of process understanding. For rare‑disease programs, agency staff may accept a flexible approach that allows completion of PPQ after licensure when supported by an approved PPQ protocol, and clinical‑stage PPQ batches may be used in clinical studies if they meet current clinical quality expectations.

The guidance also describes ways sponsors can leverage prior knowledge and shared data across related products for CMC elements such as assay and process validation, while noting that product‑specific verification data may still be required. For commercial specifications, the agency gave examples including the use of a single representative lot for assay validation with scientific justification, and the option to commit to reevaluate acceptance criteria after approval when limited lots are available at the time of BLA submission.

On stability, FDA generally recommends submitting real‑time data from three commercial lots with at least six months of data to support expiration dating, but the agency will consider alternatives supported by a risk evaluation and may accept stability data from clinical lots or highly similar products when representative of the commercial product. Schultz also encouraged sponsors to consider innovative rapid detection or alternative analytical methods for lot release testing and referenced 21 CFR 610.12 as an example of a regulation that can be applied flexibly for sterility testing.

Throughout the webinar, both presenters urged sponsors to engage early and often with their FDA review teams to discuss proposed uses of regulatory judgment, justification for leveraged data and planned acceptance criteria. "Sponsors are strongly encouraged to engage with FDA early and throughout product development," Dunn said in closing.

The presenters directed sponsors to the guidance text and to contact information on the slides for further questions and resources. The guidance is intended to clarify how FDA may apply regulatory judgment while maintaining standards to ensure products are safe, pure and potent before licensure.