Read Our Comments on FDA Guidance: Supporting Safe and Effective Cell and Gene Therapies

ASGCT is committed to advancing the field of genetic and cellular therapies to alleviate human disease. We appreciate FDA’s continued efforts to streamline and accelerate the development of safe and effective new therapies. In recent comments, ASGCT addressed two crucial draft guidance documents: Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products and Considerations for the Use of Human- and Animal-Derived Materials in the Manufacture of Cellular and Gene Therapy and Tissue-Engineered Medical Products.

Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products 

ASGCT appreciates FDA’s proactive approach in addressing the safety of human allogeneic cell-based therapies, which are rapidly advancing in the field of cell and gene therapy (CGT). This draft guidance provides a structured framework for safety testing across three categories of primary cells: extensively expanded cells, limited expansion cells, and cells administered to a few individuals. Our key asks include: 

• Clarity on Gene Editing Risks: ASGCT recommends FDA include gene editing as a distinct risk in the safety assessment of allogeneic cells, as this step may introduce unintended mutations. This addition would align with existing guidelines on genome-edited products.  

• Definition of Terms: Clear definitions for terms such as "small to midsize cell banks" and "a few individuals" are necessary to avoid ambiguity and ensure consistent application of the guidelines. 

• Interpretation of WGS Data: The large amount of data generated by whole genome sequencing (WGS) poses challenges and uncertainties in interpretation. To address this, ASGCT recommends the inclusion of a risk-based approach tailored to the stage of drug product development.  

• Use of Advanced Methods: To align with previous ICH guidelines, comments propose incorporating advanced methods such as next-generation sequencing (NGS) or high-throughput sequencing (HTS) for in vitro adventitious virus testing. 

Considerations for the Use of Human- and Animal-Derived Materials in the Manufacture of Cellular and Gene Therapy and Tissue-Engineered Medical Products 

ASGCT welcomes the FDA’s efforts in harmonizing guidelines related to the use of human- and animal-derived materials, ensuring consistency and clarity across related documents. ASGCT broadly believes that this guidance is a helpful guide for sponsors. Key asks in the Society’s response to this guidance include: 

• Stage Appropriateness: Additional phase-appropriate benchmarks or expectations for sponsors would provide much-needed clarity on the intended stage of development for this guidance. 

• Alternative Pathways: The field is increasingly moving towards chemically derived options over human- and animal-derived materials. ASGCT requested updated guidance on sponsors' use of these alternative pathways. 

• Identity Testing: The guidance suggests that sponsors should perform across-the-board identity testing for materials in Phase 1, which is not in line with generally accepted practice. ASGCT requested additional detail on the kinds of identity testing FDA recommends; as an example, starting materials and raw materials may have different considerations.  

• Data Provision: In some sections of the guidance, sponsors are asked to provide information on manufacturing materials that they may not have access to. In another area, FDA asks sponsors to provide information that should be sufficiently covered by cross-referencing a licensed product’s BLA or Master File.  

ASGCT appreciates FDA’s work to develop clear, comprehensive guidance documents that support the safety and efficacy of cell and gene therapies throughout the product lifecycle. By addressing the concerns and recommendations highlighted in our comments, the FDA can further streamline the regulatory process, reduce development delays, and ultimately enhance patient access to these transformative therapies. 

We look forward to continued collaboration with the FDA and other stakeholders to ensure that the regulatory environment supports innovation while maintaining the highest standards of patient safety. For more information on ASGCT’s comments, please read our full letters on the respective draft guidances. 

Andrew Liermann is ASGCT's Regulatory Affairs Manager.

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