January 11, 2026 - The U.S. Food and Drug Administration (FDA) issued a landmark announcement today, declaring a more flexible regulatory strategy to optimize Chemistry, Manufacturing, and Controls (CMC) requirements for Cell and Gene Therapy (CGT) products. This initiative aims to accelerate the research and development process for these products and provide clearer guidance for Biologics License Applications (BLA).
FDA Commissioner Dr. Marty Makary stated, "For highly complex and personalized therapies like CGTs, regulatory policies must be tailored. These pragmatic reforms take into account the unique characteristics of CGTs and will help stimulate more innovation."
Over the past decade, the FDA's Center for Biologics Evaluation and Research (CBER) has approved nearly 50 CGT products, leading to an explosion in product filings. As many CGT projects directly target life-threatening diseases with significant unmet medical needs, the immense potential of these therapies has not only ignited hope among patient groups but also greatly fueled R&D enthusiasm within the industry.
Traditionally, CBER applied relatively uniform CMC standards to all products, including small-batch CGTs. However, CGTs are characterized by high individuality, complex manufacturing processes, and tight time windows. Based on extensive review experience accumulated in recent years, CBER has identified and implemented a series of more adaptive regulatory measures within the existing legal framework. These measures balance technical specificities while ensuring product safety, purity, and potency.
Previously, CBER typically applied such flexibility on a "case-by-case" basis, which often led to a lack of clear expectations among stakeholders regarding regulatory standards. Through this proactive and broad communication, the FDA aims to ensure that all companies-regardless of which review team they face-understand which scientific flexibilities are acceptable. As Dr. Vinay Prasad, CBER's Chief Medical and Scientific Officer, emphasized, increasing CMC regulatory flexibility is intended to better facilitate the development of innovative products. The FDA encourages developers to actively consult with review divisions throughout the entire product development process.
Clinical Development Stage
Before commencing Phase II or Phase III clinical trials, manufacturers are not required to fully comply with the requirements of 21 CFR Part 211 (current Good Manufacturing Practice, or cGMP) (see 21 CFR 210.2(c)). The FDA will adopt a product lifecycle perspective when reviewing the validation of manufacturing processes and analytical methods. During the clinical research stage, broader product quality release criteria are permitted, as final drug substance and drug product specifications are typically determined only after the conclusion of clinical trials. When transitioning from Phase I to pivotal clinical trials aimed at confirming efficacy, CBER will accept reasonable minor manufacturing process adjustments without requiring overly burdensome comparability studies, provided that data can demonstrate comparability before and after the changes.
Commercial Quality Standards
Considering that many CGTs target rare diseases or small patient populations, making it difficult to establish traditional release standards through a large number of production batches, CBER will allow more flexible product release standards during BLA reviews, provided they are scientifically sound and consistent with product and process characteristics. After a product is launched, if a company can demonstrate stable product quality through continuous production data, CBER also supports the re-evaluation and revision of original release acceptance criteria.
Process Validation
The provision of three Process Performance Qualification (PPQ) batches for process validation is no longer mandatory. The FDA will evaluate whether the number of PPQ batches proposed by a company is sufficient and reasonable based on their understanding of the overall process. Furthermore, in specific circumstances, PPQ batches may be released before the completion of the validation protocol execution (i.e., concurrent release).
The FDA emphasized that while regulatory requirements are becoming more flexible, there will be no reduction in the fundamental safeguards for product safety, purity, and potency. Nor will these measures weaken the scientific assessment of the therapy's benefit-risk balance and the context of the disease it addresses.
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