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
Key facts
- Regulatory action: FDA direct final rule on nonclinical testing terminology
- Effective change: Replaces "animal tests/studies" with "nonclinical tests/studies"
- Legal basis: Aligned with Food and Drug Omnibus Reform Act (FDORA) of 2022
- New resource: NAMs database launched with 25 initial examples from FDA review materials
- Scope: Does not eliminate or prohibit animal studies; no new costs/requirements imposed
- Related guidance: December 2025 (mAb primate testing); March 2026 (broader NAMs guidance)
- Industry perspective: Human-derived antibody platforms already align with new framework
- Public comment: Open; rule could be withdrawn if significant adverse comments received
- Policy framework: Aligns with FDA Public Health Pillar 1 and Operation TrialBlazer
- Geography: US federal regulatory action
"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
