Precigenetics Public Comment to FDA on New Approach Methodologies

Precigenetics submitted a public comment to the FDA for Docket No. FDA-2025-D-6131, responding to the draft guidance for industry, General Considerations for the Use of New Approach Methodologies in Drug Development.

The comment supports FDA's effort to create a clearer path for human-relevant New Approach Methodologies while asking for targeted, technology-neutral clarifications that would help sponsors, technology developers, rare-disease programs, and FDA review divisions evaluate integrated NAM evidence in practice.

Summary of requested changes

Precigenetics asks FDA to make the final guidance more practical for integrated, information-rich, human biology-based NAM platforms. The requested changes focus on how sponsors should define, validate, submit, and review NAM evidence.

• Recognize integrated NAM systems. Clarify that context of use can apply to a complete measurement method or platform, not only to isolated assays or single endpoints.
• Allow modular validation. Permit multi-component NAMs to validate separable modules instead of requiring every integrated system to be treated as one indivisible black box.
• Value longitudinal evidence. Add validation considerations for continuous, time-resolved, information-rich measurements that capture biological trajectories rather than one destructive endpoint.
• Strengthen human biological relevance. Give clearer weight to non-destructive methods, expanded endpoint sets, human cell sources, and mechanism-led model composition.
• Modernize technical characterization. Expand expectations for multimodal, AI/ML-enabled, mechanism-grounded NAMs, including data quality, model behavior, reference materials, and necrosis accounting.
• Clarify fit-for-purpose review. Add an objective for integrated platform NAMs and acknowledge settings where the animal comparator is weak rather than assuming any legacy method is ground truth.
• Address rare disease and low-data settings. Clarify how FDA will weigh NAM evidence when patient-derived biology, mechanistic plausibility, and limited comparator data are central to decision-making.
• Create operational templates. Publish a structured NAM context-of-use briefing template and use structured information requests for NAM-supported submissions.
• Align incentives with better evidence. Consider cost savings, review efficiency, and Executive Order 14192 when encouraging methods that can replace low-predictive animal studies.
• Improve institutional learning. Support a public cross-species discordance registry and strengthen reviewer rubrics, specialist pairings, and NAM review capacity.

Together, these changes would help FDA evaluate NAMs by the quality and relevance of the evidence they generate, especially when newer human biology-based systems are more informative than traditional animal comparators.

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