FDA Researchers Describe How NAMs Enter Drug Review

From Scientific Methods to Reviewable Evidence

FDA researchers describe how human-relevant laboratory methods and computational approaches are moving through drug-development review in a perspective published in Clinical Pharmacology & Therapeutics. Their account covers work within the Center for Drug Evaluation and Research (CDER), interactions with developers and collaboration with other scientific organizations. The article presents the authors’ scientific views.

The perspective places recent activity within nearly two decades of CDER experience with NAMs. Computational methods and human-derived experimental systems already contribute to particular regulatory questions. A recurring task is to connect a method’s biological relevance and technical performance with the specific decision it is intended to support. That task involves review expertise, appropriate data and a clear account of how the new evidence complements other information.

Organizing Expertise Across Disciplines

The authors describe a NAMs Coordinating Committee established to connect activities across CDER. They also report a pilot NAMs Integrated Review Team launched in May 2025 to bring relevant scientific expertise into assessments that cross conventional disciplinary boundaries. An FDA-wide NAMs Program Working Group established in 2026 provides another level of coordination.

These arrangements address the fact that one method can be relevant to several therapeutic areas and types of evidence. A human cardiac model, for example, may raise questions about cell biology, electrophysiology, assay performance and clinical safety interpretation. The perspective describes cross-disciplinary coordination as a means of sharing expertise and developing more consistent approaches to the evidence.

Internal scientific reviews of cardiac and neural NAM submissions are among the activities described. They examine where methods have been used, the purposes they served and the information gaps encountered during review. This experience can inform subsequent advice, research priorities and guidance development.

Connecting Research with Regulatory Needs

The perspective discusses collaboration with the National Institutes of Health (NIH) and other partners on the development, standardization and validation of human-relevant methods. Workshops held in 2023, 2024 and 2026, together with the FDA–NIH international workshop in 2025, provided opportunities to discuss scientific progress and the evidence needed for regulatory applications.

International work is also part of the account. The authors describe updates to the ICH E14/S7B questions and answers on cardiac safety and planning for revisions to ICH S7A. Separately, FDA is a charter member of the International Medicines Regulators’ Working Group on 3Rs, with CDER serving as co-chair. Member agencies share guidance and coordinate future regulatory approaches to NAMs.

The perspective also identifies three draft guidances issued by CDER: General Considerations for the Use of New Approach Methodologies in Drug Development; Monoclonal Antibodies: Streamlined Nonclinical Safety Studies; and Quantitative Systems Pharmacology-Based Dose Selection for Minimum Anticipated Biological Effect Level in First-in-Human Trials. They address general regulatory expectations, weight-of-evidence approaches that could replace some nonhuman-primate studies and quantitative dose selection. The authors report that sponsors had already begun applying these concepts in submissions. In particular, some submissions included weight-of-evidence justifications addressing long-term safety questions for investigational monoclonal antibodies.

Two Routes for Developer Engagement

For a particular drug program, developers can discuss a proposed NAM through established interactions such as pre-IND or INTERACT meetings. The authors encourage engagement while the nonclinical strategy is being planned, including before first-in-human studies. A useful discussion connects the proposed question, the method’s role, the data available and the development decision that would follow.

A different route concerns qualification of a tool for a defined context of use. The Innovative Science and Technology Approaches for New Drugs (ISTAND) program provides a pathway for technologies outside the traditional drug-development-tool categories. Qualification can support use by multiple developers within the qualified context, whereas a program-specific review addresses the evidence needed for that particular drug.

The authors report nine NAMs qualification submissions through ISTAND in 2024 and 16 in 2025. At the time of writing in August 2026, NAMs submissions were on track to increase further. These figures describe engagement with the program; the article separately discusses the scientific work required to establish a tool’s performance and intended use.

Learning from Evidence That Reaches Reviewers

A practical difficulty is that regulators see only part of the research performed during drug development. Nonclinical work that is not submitted, proprietary datasets and uncertainty about how to present novel evidence can limit the experience available for broader learning. The authors identify data sharing and transparent scientific exchange as important ways to improve that situation.

The perspective brings these activities together as a continuing process: developers define a use, generate relevant evidence, discuss its regulatory role and refine the approach as experience accumulates. Its central contribution is an account of the people and pathways needed to make a scientifically promising method usable in a concrete drug-development decision.