What NAMs are

Definition

New approach methodologies (NAMs) are non-animal or animal-sparing methods used to assess the safety, efficacy or pharmacokinetics of drugs and chemicals. FDA groups them into in vitro human-based systems, in silico models and other platforms. EPA uses the term new approach methods for the same idea in chemical regulation.

The method families

• In vitro: human cell assays, 3D spheroids and organoids, organ-on-chip and other microphysiological systems (MPS), engineered and bioprinted tissues.
• Ex vivo: donated human tissue and whole organs kept functional by perfusion.
• In silico: QSAR and read-across, PBPK and QSP models, and machine learning models for toxicity and ADMET.
• In chemico: cell-free reactivity assays, for example peptide reactivity tests for skin sensitization.

What a NAM is not

A NAM is not automatically better than an animal study. Acceptance depends on a defined context of use: the question, the decision the data informs, and evidence that the method answers it reliably.

Why now

Three shifts converged.

1. Law. The FDA Modernization Act 2.0 (December 2022) removed the statutory animal-testing requirement for new drugs.
2. Policy. FDA's April 2025 roadmap, NIH's reorganization around human-based research, EPA's 2035 goal, the UK strategy (November 2025) and the EU chemicals roadmap (June 2026).
3. Technology. Organ-chips and organoids reached higher throughput, and AI models now train on large human-relevant datasets.

What has not changed

Most regulatory packages still include animal data. FDA's review of 15 years of submissions found NAM data concentrated in in silico and conventional in vitro methods. Organ-chip and 3D model data were less common. The shift is real but early.