NAMs & Regulatory Acceptance – Part 2/3: How EMA and FDA Are Embracing NAMs

Published on: April 2026

EU and US regulators now offer clear routes to discuss and qualify New Approach Methodologies (NAMs — from early scientific dialogue to method qualification or validation for a defined Context of Use (CoU). This guide outlines which pathway to use, when to engage, and what type of evidence is expected.

Why this guide?

In Blogpost Part 1, we explored why regulators are accelerating the adoption of NAMs and the scientific and regulatory momentum behind this shift. This second article focuses on the “how”: the concrete EMA and FDA touchpoints, the typical timing of interactions, and the type of evidence that makes these exchanges productive.

Your fast map to EU & US pathways

In the European Union, the EMA Innovation Task Force (ITF) is often the preferred entry point for early dialogue between regulators and NAM developers, including academic researchers, SMEs, and large pharmaceutical companies.

Between 2019 and 2023, the most frequently discussed topics in 3Rs-related ITF briefing meeting requests were safety and toxicology. The main risks assessed included drug-induced liver injury (DILI) and cardiotoxicity using in vitro models, as well as in silico and in vitro prediction of off‑target effects for gene‑editing systems.

Figure 1. Medicine development topics addressed in 3Rs‑related ITF briefing meeting requests (2019–2023).
Adapted from New Approach Methodologies – EU‑IN Horizon Scanning Report, EMA/56850/2025.

Figure 2. Number of ITF briefing meeting requests focusing on a specific issue (A) or NAM (B) out of 36 ITF meeting requests, covering a total of 46 NAMs presented between 2019 and 2023.
Adapted from New Approach Methodologies – EU‑IN Horizon Scanning Report, EMA/56850/2025.

In the United States, sponsors and NAM developers are similarly encouraged to engage early with the Food and Drug Administration (FDA) on the potential use of NAMs. These discussions can take place through INTERACT meetings, Pre‑IND interactions, Type C or Type D meetings, or written responses. For discussions outside of a regulatory application, Critical Path Innovation Meetings (CPIM) are also available.

Developers may additionally present new methods to the FDA through Alternative Methods Working Group (AMWG) webinars. During 2022 and 2023, developers presented 29 webinars describing in silico models and in vitro platforms such as microphysiological systems, organoids, and engineered tissues. These methods addressed contexts including drug‑induced liver injury, neurotoxicity, and inhalation toxicity.

Seeking formal qualification of a NAM for a specific Context of Use (CoU) remains voluntary. NAMs that have not been qualified—or that are qualified for a different CoU—may still be used in regulatory applications when scientifically appropriate, subject to agreement with the relevant FDA review division or office.

For developers pursuing NAM qualification, regulatory advice is available before and throughout the process via the Innovative Science and Technology Approaches for New Drugs (ISTAND) Program. These interactions help identify challenges and opportunities, guide data generation, refine the proposed CoU, and clarify expectations regarding the level of evidence required at each stage.

What’s next?

Stay tuned for Blogpost Part 3, which will focus on validation, qualification, and fit‑for‑purpose principles, and how they help build regulatory confidence in NAMs.