The FDA has announced additional details regarding its flexible approach to overseeing chemistry, manufacturing, and control (CMC) requirements for cell and gene therapies, which the agency expects to help expedite product development and guide the evaluation of development strategies necessary for the preparation of biologics license application (BLA) submissions.1,2
The update, released on January 11, 2026, describes how the FDA will apply regulatory flexibility across clinical development, commercial specifications, and process validation to better align oversight with the unique scientific, manufacturing, and clinical characteristics of cell and gene therapies.
“Regulatory flexibility must be tailored for cell and gene therapies,” FDA Commissioner Marty Makary, MD, MPH, commented in a news release.2 “These are common-sense reforms that will address the unique characteristics of cell and gene therapies and foster more innovation.”
FDA CMC Flexibility Updates for Cell and Gene Therapies
- The FDA has shared information on its new flexible approach to CMC oversight for cell and gene therapies to help speed development and inform BLA strategies.
- The agency noted that it reviews process and method validation using a product lifecycle framework; as part of its approach, the FDA does not require manufacturers to comply with 21 CFR part 211 prior to product manufacturing in phase 2/3 trials and may allow permissive release criteria and minor changes with comparability data.
- The FDA may also offer flexibility in process validation, and will consider flexibility, when appropriately justified, in establishing product release specifications during BLA review.
How is the FDA increasing CMC flexibility during clinical development for cell and gene therapies?
As part of its approach, the FDA reiterated that manufacturers are not expected to comply with current good manufacturing practice requirements under 21 CFR part 211 in the code of federal regulations before an investigational product is manufactured for phase 2 or phase 3 clinical trials.1
The agency noted that it reviews process and method validation using a product lifecycle framework, recognizing that validation strategies are refined as development progresses. Because final specifications for drug substance and drug product are not expected until the end of the investigational process, investigational new drug (IND) applications may include permissive product quality release acceptance criteria that are appropriate for investigational use and aligned with applicable quality requirements.
As sponsors advance from phase 1 studies to trials designed to establish efficacy for licensure, the FDA’s Center for Biologics Evaluation and Research (CBER) indicated that it will allow minor manufacturing changes, provided they are supported by data demonstrating comparability between pre-change and post-change product and do not require overly burdensome comparability data packages.
How is the FDA increasing flexibility around commercial specifications?
The FDA noted that its approach to commercial specifications reflects the need to ensure product quality and regulatory compliance while accounting for the small patient populations often targeted by cell and gene therapies, which may limit the number of manufacturing lots available to support traditional product release specifications.
The FDA’s CBER stated that it will consider flexibility, when appropriately justified, in establishing product release specifications during BLA review; this flexibility should be consistent with the nature of the product and its manufacturing process. In addition, the agency will also consider submissions seeking to re-evaluate and revise product release acceptance criteria based on post-approval manufacturing experience, particularly when manufacturers can demonstrate consistent product quality over time.
How does the FDA’s revised approach increase process validation flexibility for cell and gene therapies?
With respect to process validation, the FDA outlined additional flexibility tailored to cell and gene therapies manufacturing, including that there may be circumstances in which specific process performance qualification lots are designed for release and distribution before all protocol execution steps are completed (i.e. concurrent release).
The FDA also clarified that process validation does not require three process performance qualification lots to be supplied. Instead, the agency’s review may evaluate whether the process performance qualification protocol adequately justifies the number of lots proposed, based on overall process understanding and product-specific considerations.
“There has been tremendous enthusiasm amongst product developers resulting in an explosive growth of cell and gene therapy submissions, many of which target serious or life-threatening conditions with an unmet medical need,” Vinay Prasad, MD, MPH, chief medical and scientific officer and director of the FDA’s CBER, concluded in the news release.2 “CBER is eager for stakeholders to know that our effectiveness at exercising greater regulatory flexibility around chemistry, manufacturing and control requirements furthers innovative product development.”
References
- Flexible requirements for cell and gene therapies to advance innovation. FDA. News Release. January 11, 2026. Accessed January 12, 2026. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/flexible-requirements-cell-and-gene-therapies-advance-innovation?utm_medium=email&utm_source=govdelivery
- FDA increases flexibility on requirements for cell and gene therapies to advance innovation. FDA. Updated January 11, 2026. Accessed January 12, 2026. https://www.fda.gov/news-events/press-announcements/fda-increases-flexibility-requirements-cell-and-gene-therapies-advance-innovation
