The U.S. Food and Drug Administration has released draft guidance outlining how New Approach Methodologies (NAMs) can be validated and used in regulatory submissions as alternatives to animal testing in drug development.
Written By: Sana Khan BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration has released a draft guidance outlining how New Approach Methodologies (NAMs) can be validated and used in regulatory submissions as alternatives to animal testing in drug development. The document provides recommendations from the agency’s Center for Drug Evaluation and Research (CDER) on how sponsors can generate and submit nonclinical NAM data in support of drug applications or in response to orders issued under section 505G of the Federal Food, Drug, and Cosmetic Act for OTC monographs.
According to the FDA, the guidance marks another step in the agency’s broader roadmap to reduce reliance on animal testing and promote human-relevant scientific approaches in drug development. The document outlines general validation considerations when NAM-based data are submitted to support regulatory decision-making.
HHS Secretary Robert F. Kennedy Jr. said the draft guidance is intended to advance efforts to replace animal testing with scientifically rigorous human-relevant methods. He added that clearer validation expectations could help modern technologies gain regulatory confidence and accelerate the development of safer and more effective therapies.
Similarly, FDA Commissioner Marty Makary noted that technological advances are enabling the adoption of modern testing systems that move beyond traditional animal models in regulatory submissions.
The guidance describes several categories of NAMs that may be used to support nonclinical drug development data, including complex and two-dimensional in-vitro laboratory studies; three-dimensional biological models such as organoids, spheroids, and organs-on-chips; chemical reactivity studies; computer simulations or in-silico modeling approaches; and studies involving phylogenetically lower organisms such as zebrafish or C. elegans.
According to the FDA, validated NAMs can help identify toxicities, demonstrate how investigational drugs work, improve the predictivity of nonclinical studies, and enhance the safety of future clinical trials.
The draft guidance establishes four core validation principles that sponsors should consider when validating NAMs for regulatory use. These include clearly defining the context of use, referring to the intended regulatory purpose of the methodology and how it will support decision-making in drug development or regulatory review.
The framework also requires demonstration of human biological relevance, meaning the approach should be capable of assessing toxicity or biological effects relevant to human physiology. In addition, sponsors must ensure technical characterization, demonstrating that the method is scientifically robust, reliable, and reproducible.
Finally, the NAM must be fit-for-purpose, indicating that the data generated are suitable for regulatory evaluation, including informing drug review and potential approval decisions by the FDA.
The FDA emphasized that the draft guidance provides general validation considerations rather than detailed requirements for specific technologies or drug discovery applications. Sponsors planning to use NAMs are encouraged to consult with the appropriate FDA review division, particularly when developing methods tailored to specific diseases, organs, endpoints, or indications.
Acting CDER Director Tracy Beth Hoeg said the agency aims to shift drug development toward approaches where human-centric models can more reliably and efficiently predict human drug responses prior to clinical trials.
References:
FDA Releases Draft Guidance on Alternatives to Animal Testing in Drug Development, 18 March 2026, https://www.fda.gov/news-events/press-announcements/fda-releases-draft-guidance-alternatives-animal-testing-drug-development
General Considerations for the Use of New Approach Methodologies in Drug Development Guidance for Industry, March 2026, https://www.fda.gov/media/191589/download
About the Writer
Sana Jamil Khan is a B.Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.