Comment from ProtaGene CGT

ProtaGene appreciates the opportunity to comment on the FDA draft guidance, “Safety Assessment of Genome Editing in Human Gene Therapy Products Using Next-Generation Sequencing” (Docket No. FDA-2026-D-1255), and supports the Agency’s efforts to provide a clear and science-based framework for the safety assessment of genome-edited human gene therapy products. ProtaGene is a contract research organization (CRO) supporting the biopharmaceutical and cell and gene therapy industries. From research through commercialization, ProtaGene provides biosafety assessment services, including on- and off-target analysis, integration site analysis, and genome integrity assessment using next-generation sequencing technologies. We agree that comprehensive characterization of intended and unintended genome editing outcomes is essential to ensure patient safety. In particular, sensitive detection of low-frequency off-target events, unintended on-target modifications, and broader impacts on genome integrity should be a key component of safety assessment. Our comments focus on strengthening the guidance through greater clarity regarding sequencing technology selection, assay performance expectations, use of clinically relevant cell models and editing conditions, off-target nomination and confirmation strategies, and genome integrity assessments. We also emphasize the importance of evaluating a broad range of structural genomic alterations and highlight integration site analysis as a critical element of safety assessment whenever DNA-based editing reagents, donor templates, or delivery vectors are used. Overall, we believe the draft guidance provides an important foundation for the application of NGS technologies in genome editing safety assessment. Additional clarification in the areas outlined in our comments would further support consistent implementation across the field and the safe development of genome-edited human gene therapy products.See attached file(s)