Federal draft guidance focuses on alternative methods to animal testing

Officials with the FDA have released a draft guidance that aims to help drug developers validate new approach methodologies (NAMs) that can be used in place of animal testing. Based on human-centric data, safe and effective drugs would be brought to the market sooner, according to the agency.¹

The draft guidance marks a significant milestone in the implementation of the FDA’s roadmap to reducing animal testing, and reflects the FDA's commitment to moving away from using animal testing as the default method for gaining drug safety information. The draft guidance describes the Center for Drug Evaluation and Research’s (CDER’s) general recommendations to consider for validating NAMs when nonclinical NAMs data are provided in support of a drug application or regarding an order issued under section 505G of the FD&C Act for an over-the-counter monograph.

Under the FDA’s regulations, drug sponsors must submit nonclinical pharmacology and toxicology data before investigational drugs can proceed to clinical trials. Although many studies have traditionally been conducted in animals, CDER routinely reviews data from NAMs when the methodology demonstrates reliability and scientific validity.

"Technological advances are allowing us to move beyond animal testing in drug development, which has a poor track record of predicting safety and efficacy in humans," Marty Makary, MD, MPH, commission for the FDA, said in a news release. "This guidance will facilitate the adoption of modern alternatives to animal testing in regulatory submissions."

Examples of NAMs include testing approaches such as complex and 2-dimensional in vitro studies; 3-dimensional models such as organoids, spheroids and organs on chips; chemical reactivity studies; computer simulations or in-silico modeling; and studies using “phylogenetically lower” animals such as zebrafish or C. elegans, according to the FDA. There are also several examples of validated NAMs outperforming unvalidated animal models in predicting human responses to drugs. NAMs can identify toxicities, demonstrate how the investigational drug works, improve predictivity of nonclinical studies, and enhance the safety of future clinical trials.

This draft guidance establishes four core validation principles for NAMs:

• Context of use: Clear definition of NAMs’ intended regulatory purpose
• Human biological relevance: Demonstration of how NAMs can assess toxicity
• Technical characterization: Establishment of scientific confidence through robust, reliable, and reproducible methods
• Fit-for-purpose: Assurance that NAMs help in regulatory decision-making (eg, drug review and potential approval)

Although the guidance provides general validation considerations for NAMs used in drug development, it does not address specific methodologies or drug discovery applications. The FDA encourages drug developers to consult with the agency’s appropriate review division when considering NAMs, particularly for indication-, disease-, organ-, and endpoint-specific applications.

“It is time for the FDA to shift the drug development paradigm away from the current default of using animals to predict human responses to one where these data are obtained through human-centric models which can more reliably, efficiently and ethically predict human drug reactions prior to clinical trials,” Tracy Beth Hoeg, MD, PhD, acting director for the CDER, said in the release.

The FDA’s release of this new draft guidance follows draft guidance released in December 2025 for the reduction of testing on nonhuman primates for certain monoclonal antibodies. Additionally, the FDA has announced a level 2 revision of the final guidance titled, “Guidance for Industry Pyrogen Endotoxins Testing–Questions and Answers,” to clarify the agency’s current thinking on pyrogen endotoxins testing. This action provides clarity to manufacturers seeking to transition to the use of recombinant reagents for bacterial endotoxin testing of drugs and devices regulated by FDA.

Reference

FDA releases draft guidance on alternatives to animal testing in drug development. News release. FDA. March 18, 2026. Accessed March 19, 2026. https://www.fda.gov/news-events/press-announcements/fda-releases-draft-guidance-alternatives-animal-testing-drug-development