FDA Finalizes Guidance on Manufacturing Flexibility for Cell and Gene Therapy Filings

The US Food and Drug Administration has issued final guidance describing how it applies flexibility to chemistry, manufacturing and controls (CMC) requirements for cell and gene therapy products headed for a biologics license application (BLA). The guidance, dated May 2026 and issued by the Center for Biologics Evaluation and Research (CBER), was released on Tuesday, May 5, according to AABB, which described it as final level 2 guidance.

"Consistent with the statutory and regulatory requirements for biological products, FDA uses a flexible approach to ensuring applicable CMC requirements are met for CGT products," the agency states on the guidance page. It says that approach "serves to help expedite development, review, and patient access to safe and effective CGT products to treat serious or life-threatening conditions that represent significant unmet medical needs."

The FDA also says the document covers when flexibilities may be appropriate but "does not comprehensively address the CMC information and data necessary to support CGT product licensure" under section 351 of the Public Health Service Act. Sponsors are told to read it alongside the agency's other CMC guidances for these products.

Where the flexibility applies

The guidance took immediate effect, Regulatory Focus reported on May 8. According to its summary, FDA acknowledged that traditional development strategies can be hard to apply to these products because of complex processes, individualized manufacturing, small patient populations, fewer manufacturing runs and short shelf lives.

Development-stage flexibilities listed in the guidance include phase-appropriate current good manufacturing practices, release acceptance criteria suited to the stage of the investigational study, a risk-based approach to comparability studies, use of prior knowledge and use of voluntary consensus standards, Regulatory Focus reported.

For process validation, sponsors can develop a process performance qualification (PPQ) approach that "scientifically supports the number of PPQ batches submitted to the BLA." FDA wrote that it "may consider allowing concurrent release of PPQ batches for commercial use after BLA approval if the batches meet the commercial release specification and are within the commercial shelf life."

On commercial specifications, the guidance allows a release strategy matched to the "nature of the product, the manufacturing process, and the number of lots available," and sponsors may consider using fewer lots, including a single representative lot, if the analytical method validation strategy is scientifically supported, Regulatory Focus reported. Other provisions cover using clinical-lot stability data to set commercial expiration dates, possible exceptions to reserve-sample retention for small or individualized lots, and alternative test methods that use less sample or time.

Meet first, FDA says

The guidance applies to products regulated by CBER, and FDA said sponsors should meet with the agency to discuss a CMC approach before putting it into practice, according to Regulatory Focus. Regulatory Focus described it as the third cell and gene therapy guidance FDA has released in 2026, after draft guidances on genome editing safety assessments and on a plausible mechanism framework for individualized therapies.

At a recent public meeting hosted by Friends of Cancer Research and the Parker Institute for Cancer Immunotherapy, Allogene Therapeutics chief technical officer Ben Beneski said he thinks the final guidance would be "really helpful in real-world situations" where products have limited engineering runs or data, the publication reported. Kimberly Schultz, a division director in CBER's Division of Cellular and Gene Therapies, said at the same meeting that FDA promotes "a lifecycle approach to specification setting."

Comments on the guidance can be submitted to docket FDA-2026-D-4692 at any time, according to the FDA page.