FDA Publishes Draft Guidance on Human Cellular and Gene Therapy Products

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The document’s recommendations outline what studies and reports are required for changes to cell and gene therapy manufacturing.

FDA published a draft guidance document on July 13, 2023 outlining recommendations for manufacturing of products related to human cellular therapy or gene therapy (CGT). Recommendations included product compatibility and manufacturing changes regarding investigational and licensed CGT products. The draft guidance document reflected FDA’s current view on “management and reporting of manufacturing changes for CGT products based on a lifecycle approach, and comparability studies to assess the effect of manufacturing changes on product quality.”

The guidance specifically talks about considerations for the management of manufacturing changes related to risk management, stability and delivery device compatibility, nonclinical studies, and clinical students. It then covers regulatory reporting of manufacturing changes. This included chemistry, manufacturing, controls (CMC) changes requiring a new Investigational New Drug Application (IND) submission, and reporting manufacturing changes to an IND and to a Biologics License Application (BLA). Comparability assessment and reporting are also discussed, touching on risk assessment, analytical comparability study design, analytical methods, results, and statistics. There is also a section for special considerations for tissue-engineered medical products.

Due to the complexity of CGT products and the unique factors present in manufacturing and control of CGT products, making changes to their management and manufacturing may be more of a challenge than for other biological products. While product manufacturers may seek to make a manufacturing chance for many reasons, it is important that the risks to product quality be properly assessed beforehand. The guidance states, “Risk assessment should be performed for all types of manufacturing changes, regardless of the stage of product development. If a risk assessment indicates that a manufacturing change has the potential to adversely affect product quality, comparability studies should be performed to evaluate the impact of the proposed manufacturing change.”


Sponsors and applicants of CGT products were recommended to discuss significant manufacturing changes with FDA’s Center for Biologics Evaluation and Research, especially if the changes would take place in later stages of the product lifecycle.

Source: FDA