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by Aisha Khan, PhD, MBA
Clinical Research Cellular Manufacturing Program
Interdisciplinary Stem Cell, University of Miami Miller School of Medicine

The FDA has issued a draft guidance aimed at addressing the complex considerations involved in the use of human- and animal-derived materials in the production of Cell and Gene Therapy (CGT) products and Tissue-Engineered Medical Products (TEMPs)1. This guidance highlights critical areas of focus, including the risks of transmitting adventitious agents, ensuring material consistency, and managing risk in the manufacturing process. By providing clear recommendations on the safe use of these materials, the guidance seeks to ensure the safety, quality, and efficacy of advanced therapeutic products.

Key Features of the FDA Guidance:

1. Introduction and Background: Manufacturing CGT products and TEMPs often requires the use of human- and animal-derived materials, including cells, proteins, and reagents. These materials introduce unique safety and quality challenges, particularly related to the transmission of infectious agents and material consistency. Recognizing the potential for contamination and variability, the FDA’s guidance offers manufacturers comprehensive recommendations for mitigating risks and ensuring the safety and integrity of these products.
2. Ensuring Safety and Risk Management: A key focus of the guidance is the management of risks associated with adventitious agents, such as viruses, bacteria, mycoplasma, and transmissible spongiform encephalopathies (TSEs), which could be introduced through human- or animal-derived materials. The FDA emphasizes the need for thorough material testing, validation of manufacturing processes, and proper risk management protocols to prevent contamination. Manufacturers are advised to adopt a systematic approach to assessing risks at every stage of production, ensuring that human- and animal-derived materials are thoroughly screened and appropriately managed.
3. Material Testing and Consistency: The guidance underscores the importance of material identity and consistency. Differences between material lots, such as variations in growth media supplements, can lead to product inconsistencies. To address these concerns, manufacturers are encouraged to implement stringent testing protocols and acceptance criteria for all human- and animal-derived materials. The use of well-characterized, high-quality materials is critical for ensuring the reproducibility of manufacturing processes and the quality of the final product.
   Regulatory Submissions and Compliance: Manufacturers of CGT products and TEMPs must submit detailed Chemistry, Manufacturing, and Control (CMC) information to the FDA as part of an investigational new drug (IND) application. The guidance outlines the necessary documentation for human- and animal-derived materials, including supplier qualifications, material sourcing, and testing procedures. Compliance with Good Manufacturing Practice (GMP) regulations2-4 is also emphasized, with manufacturers expected to maintain rigorous quarantine and material acceptance protocols.
4. Focus on Innovation and Safety: The FDA encourages the use of alternative materials that are free from human- and animal-derived components, such as recombinant proteins and synthetic culture media. These alternatives reduce the risks of contamination and variability associated with biological materials while supporting the development of safe and consistent products.

The FDA’s guidance on the use of human- and animal-derived materials in CGT and TEMP manufacturing provides a robust framework for ensuring product safety and consistency. By following these recommendations, manufacturers can better manage risks, improve product quality, and ultimately advance the development of safe and effective therapies.

References:

1. U.S. Food and Drug Administration. (2024). Considerations for the use of human-and animal-derived materials in the manufacture of cell and gene therapy and tissue-engineered medical products. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-human-and-animal-derived-materials-manufacture-cell-and-gene-therapy-and-tissue
2. U.S. Food and Drug Administration. (2016). Q7 good manufacturing practice guidance for active pharmaceutical ingredients; Guidance for industry. https://www.fda.gov/media/71518/download
3. U.S. Food and Drug Administration. (2020). Chemistry, manufacturing, and control (CMC) information for human gene therapy investigational new drug applications (INDs); Guidance for industry. https://www.fda.gov/media/113760/download
4. U.S. Food and Drug Administration. (2008). Guidance for FDA reviewers and sponsors: Content and review of chemistry, manufacturing, and control (CMC) information for human somatic cell therapy investigational new drug applications (INDs). https://www.fda.gov/media/73624/download