FDA Formalizes Non-Animal Testing Methods in New Rule

FDA has issued a direct final rule updating its regulations to clarify that non-animal methods can be used, where appropriate, to test the safety of drugs and biological products intended for human use before they are tried in humans, the agency announced September 21, 2026.¹ The rule replaces terms such as "animal tests" and "animal studies" with "nonclinical tests" and "nonclinical studies," reflecting advances in testing methods that include human cells, organs-on-chips, and computer models.¹

"This new rule supports the Trump Administration's push to explore ways to complement, or where appropriate, replace animal studies with methods that may better predict how medicines will actually affect people," said Kyle Diamantas, JD, acting FDA commissioner, in an agency press release.¹ "It gives scientists and drug developers greater flexibility to use the testing approach that best addresses their scientific question. Our goal is not to replace one rigid approach with another. It is to support rigorous, modern science—including animal studies when they remain appropriate and validated alternatives when they can provide the evidence needed to protect patients."

What does the new rule change?

The rule defines "nonclinical test" and "nonclinical study" in line with the Food and Drug Omnibus Reform Act of 2022, which recognized newer non-animal methods and traditional animal studies as possible ways to generate evidence needed to begin studies in people.¹ The rule removes language that could suggest animal testing is the only acceptable way to generate safety information for regulatory decisions, but it does not eliminate or prohibit animal studies, change evidentiary standards, or impose new costs or requirements on drug developers. To demonstrate practical application, FDA also launched a database of new approach methodologies (NAMs) examples, with an initial release of 25 examples drawn from publicly available FDA review materials.¹

How does this fit into FDA's broader NAMs strategy, and what are industry perspectives?

The rule builds on earlier FDA guidance encouraging non-animal approaches, including a December 2025 draft guidance on streamlined non-clinical safety studies for monoclonal antibodies that could reduce or eliminate long-term primate toxicology studies,² and a March 2026 draft guidance formalizing computational models and in vitro human-based systems as primary evidence in safety packages.³

Speaking about how these guidances affect antibody developers whose platforms rely on human-derived data, Wyatt McDonnell, PhD, CEO of Infinimmune, said in a previous interview with BioPharm International®, an Industry Sciences 1 brand, "Every species transition is a chance for something to break or to select for a false negative, and every re-engineering cycle costs both time and money."⁴ McDonnell noted that animal studies have not been eliminated entirely under the new guidelines, but that they shift how much animal-derived data is required in an investigational new drug package.⁴

What else is FDA doing to advance this effort?

These actions align with Pillar 1, Innovation and Global Leadership, of FDA's Public Health Pillars, and complement Operation TrialBlazer, a Department of Health and Human Services initiative to modernize clinical research and accelerate treatment development.¹ The agency is inviting public comment on the rule, including from clinicians, caregivers, the scientific community, and industry. If the agency receives significant adverse comments on the direct final rule, it will withdraw it and continue rulemaking through the standard notice-and-comment process using a companion proposed rule published simultaneously.¹

What are the limitations?

The rule updates terminology and regulatory flexibility rather than establishing new validation standards for specific non-animal methods. Under the new rule, developers must still demonstrate that any method used is adequately validated and appropriate for the specific product and regulatory question. The rule remains subject to public comment and could be withdrawn if significant adverse comments are received.

References

1. FDA. FDA updates regulations to advance innovative alternatives to animal testing. Press release. Published September 21, 2026. Accessed September 23, 2026. https://www.fda.gov/news-events/press-announcements/fda-updates-regulations-advance-innovative-alternatives-animal-testing
2. FDA. FDA releases draft guidance on reducing testing on non-human primates for monoclonal antibodies. Press release. Published December 2, 2025. Accessed September 23, 2026. https://www.fda.gov/news-events/press-announcements/fda-releases-draft-guidance-reducing-testing-non-human-primates-monoclonal-antibodies
3. FDA. FDA releases draft guidance on alternatives to animal testing in drug development. Press release. Published March 18, 2026. Accessed September 23, 2026. https://www.fda.gov/news-events/press-announcements/fda-releases-draft-guidance-alternatives-animal-testing-drug-development
4. Mirasol F, McDonnell W. Dr Wyatt McDonnell, Infinimmune CEO, highlights why human-derived antibody platforms align with FDA's non-animal model framework. BioPharm International. Published June 29, 2026. Accessed September 23, 2026. https://www.biopharminternational.com/view/wyatt-mcdonnell-infinimmune-ceo-human-derived-antibody-fda-non-animal-model