FDA Issues Final Guidance on CMC Flexibility for Cell and Gene Therapy BLAs

The Food and Drug Administration released final level 2 guidance on Tuesday outlining how it applies chemistry, manufacturing and controls (CMC) flexibility for human cellular and gene therapy (CGT) products submitted under biologics license applications (BLAs).

The guidance describes a risk-based, flexible approach to CMC requirements intended to support more efficient development and review of CGT products, particularly those targeting serious or life-threatening conditions with unmet medical needs. It also outlines where flexibility may be applied, including phase-appropriate manufacturing controls and, in some cases, acceptance of smaller or evolving datasets early in development for complex or low-volume products.

FDA emphasized that the guidance provides information on when CMC flexibilities may be appropriate for the development of CGT products 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 (42 U.S.C. 262). The agency advised sponsors to consider this guidance alongside other applicable CMC recommendations when developing CGT products.