Safety Assessment of Genome Editing in Human Gene Therapy Products Using Next-Generation Sequencing; Draft Guidance for Industry

The Alliance for Regenerative Medicine (ARM) supports the FDA's draft guidance on the safety assessment of genome editing in human gene therapy products. They recommend refining the guidance to ensure it remains risk-based, modality-specific, and proportionate to the biological risk of different editing technologies.

The American Society of Gene & Cell Therapy (ASGCT) supports the draft guidance on NGS-based safety assessment of human genome editing products. They request additional clarity on assay performance principles, emerging editing modalities, and specific parameters for off-target and chromosomal integrity analysis to ensure consistent implementation across the industry.

PhRMA, representing leading biopharmaceutical companies, supports the FDA's draft guidance on genome editing safety assessments. They advocate for a risk-based, "fit-for-purpose" regulatory framework that provides more clarity on analytical thresholds, off-target site filtering, and specific requirements for different editing modalities to ensure regulatory predictability and innovation.

CureDuchenne, an advocacy organization for Duchenne muscular dystrophy, supports the FDA's draft guidance on genome editing safety assessments but urges the agency to adopt a more flexible, risk-based approach. They argue that for severe rare diseases, the regulatory framework should prioritize timely patient access by allowing for alternative model systems and staged data generation to avoid development delays.

Christopher Freeman supports the FDA's efforts to establish a rigorous framework for genome editing safety but argues that the guidance should be more flexible for rare and ultra-rare diseases. He recommends a "fit-for-purpose" approach that accounts for limited biological samples, emphasizes non-animal methods, and prioritizes the functional relevance of off-target findings over simple enumeration.