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FDA updates nonclinical testing terminology to recognise NAMs as part of animal-reduction drive

🇺🇸 FDA CBER · Fri 06 Nov 2026

A direct final rule clarifies that nonclinical tests can include cell-based assays, organs-on-chips and computer models, without mandating any method or changing evidentiary standards.

The US Food and Drug Administration has updated the CBER-hosted New Approach Methodologies (NAMs) page. It now reports that, in September 2026, the agency issued a direct final rule revising terminology in the regulations governing human drug and biological product development.

According to the agency, the rule reflects federal law by recognising that nonclinical tests may include NAMs, such as cell-based assays, organs-on-chips and computer models, alongside nonhuman in vivo testing. The FDA stresses that it does not require a particular method and does not change its evidentiary standards. A companion proposed rule was published in the same issue of the Federal Register, so the agency can proceed by that route if the direct final rule is withdrawn after significant adverse comments.

The page also points to a follow-up report, Reducing Animal Testing in Nonclinical Studies: Year One Progress and the Path Forward. It summarises progress on the agency's roadmap and sets out next steps. The FDA says it has launched several key initiatives since the roadmap was published and describes the first-year goals as achieved. It argues that over 90% of drugs found safe in animals fail in humans, and presents NAMs, including AI-powered models, organ-on-a-chip systems and real-world data, as better predictors of human response.

The FDA defines NAMs as innovative methods and strategies for assessing the safety, efficacy and quality of FDA-regulated products. These include in vitro human-based systems and in silico modelling that can collectively evaluate immunogenicity, toxicity and pharmacodynamics. The page lists several routes for engaging with the agency: the ISTAND programme, Critical Path Innovation Meetings, INTERACT meetings, pre-IND meetings and Drug Development Tool qualification programmes. It also links to a database of NAM use-case examples drawn from publicly available application review materials.

A separate data request seeks information on whether the pH cycling test model should be accepted as a nonanimal testing procedure for fluoride toothpaste under OTC Monograph M021 (Anticaries Drug Products for OTC Human Use). The page does not give a deadline for responses.

What it means for your team

  • The direct final rule changes terminology only. The FDA says it imposes no required method and leaves evidentiary standards unchanged, so existing nonclinical packages are not affected by it alone.
  • Regulatory teams considering NAM-based data can use the interaction routes the FDA lists (ISTAND, CPIM, INTERACT, pre-IND meetings, DDT qualification) to test acceptability early.
  • Teams should monitor the Federal Register for the outcome of the direct final rule, because the companion proposed rule would apply if significant adverse comments force its withdrawal.
  • Sponsors of OTC fluoride dentifrice products may wish to review the data request on the pH cycling test model under monograph M021.

Official source: FDA CBER ↗

Article written by VigiEye from the official source (FDA CBER). AI-assisted; check the source before acting.

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