NAMs & Regulatory Acceptance – Part 1/3: Why Regulators Are Accelerating a Scientific Shift

Published on: April 2026

A new generation of New Approach Methodologies (NAMs) is driving NAMs regulatory acceptance, moving from scientific promise to regulatory reality.—from organ‑on‑chip to AI models—is moving from scientific promise to regulatory reality. The EU and the US have opened concrete pathways so innovators can bring NAMs into real development programs.

Figure 1. Examples of NAMs: Microphysiological systems (MPS) including Organ-on-Chip (OoC)
Adapted from EMA Concept paper on the revision of the Guideline on the principles of regulatory acceptance of 3R’s principle-testing approaches.

Why NAMs, why now?

NAMs enable human‑relevant insights earlier, improve decision quality, and advance the 3Rs—Reduce, Refine, Replace animal use—originally framed by Russell & Burch in 1959 and now embedded in modern regulatory science.

Beyond ethics, the prize is predictivity: mechanistic understanding that helps sponsors de‑risk faster and regulators weigh patient benefit–risk with more confidence.

The regulatory mood: from exploration to implementation

Regulators have already integrated specific NAMs into guidance and regulatory review. Examples include the Bovine Corneal Opacity and Permeability (BCOP) assay for ocular irritation, Reconstructed Human Epidermis models for skin endpoints, the Comprehensive in vitro Proarrhythmia Assay (CiPA) for cardiac risk using human induced pluripotent stem cell (hiPSC) cardiomyocytes, quantitative structure–activity relationship (QSAR) models for mutagenic impurities under ICH M7(R2), and weight‑of‑evidence (WoE) approaches under ICH S1B(R1).

Regulatory authorities such as the Food and Drug Administration (FDA), European Medicines Agency (EMA), Medicines and Healthcare products Regulatory Agency (MHRA), and the Pharmaceuticals and Medical Devices Agency (PMDA, Japan) have emphasized their continued commitment to integrating NAMs into regulatory science and actively encourage NAM users and developers to engage in early dialogue.

A new method will be considered when it provides meaningful added value by generating robust, reliable, and decision‑relevant information, and when it improves the predictivity, reliability, and human relevance of nonclinical tests. These attributes help regulators determine how a NAM fits within existing frameworks or whether its adoption could contribute to their modernization.

What can NAM users and developers do?

Several routes exist for NAM users and developers to engage regulators and discuss the concept, development, acceptability, or intended use of a new method. These pathways vary by region but share a common objective: ensuring that NAMs deliver robust, reliable, and decision‑relevant information to support human safety and drug development.

Early and structured engagement is key to clarifying expectations, aligning on evidentiary requirements, and maximizing the likelihood of regulatory acceptance.

What’s next?

Stay tuned for Blogpost 2, which will provide a practical overview of EU and US regulatory advice pathways, offering a clear, side‑by‑side view of available engagement mechanisms and guidance on when to use them.