General Considerations for the Use of New Approach Methodologies in Drug Development; Guidance for Industry - Draft Guidance

Precigeneics, Inc., a nonclinical drug development platform company, strongly endorses the draft guidance and its four-pillar validation framework. They provide fourteen specific recommendations aimed at making the framework more operationally credible for integrated, AI/ML-enabled New Approach Methodologies (NAMs) without lowering evidentiary standards.

Nexus Concordat Inc., a company led by an inventor of AI/ML-related patents, supports the FDA's draft guidance but argues that the current framework fails to address the architectural non-determinism of commercial Large Language Models. They propose a two-tiered acceptance framework that distinguishes between "procedurally wrapped" models and "substrate-level credentialed" architectures that ensure reproducibility and auditability by construction.