On September 21, 2026, the U.S. Food and Drug Administration issued a direct final rule clarifying that non-animal testing methods may be used, when appropriate, to generate safety information for drugs and biological products intended for human use before those products are tested in people. The rule aims to expand the range of acceptable testing approaches in human drug development while maintaining existing standards for protecting patients.
The agency described the change as a response to scientific and technological advances that have broadened options for safety assessment, including human-cell models, organs-on-chips, computational models and other advanced technologies.
The rule replaces language such as “animal tests,” “animal studies,” “preclinical,” and “in vitro” with the terms “nonclinical tests” and “nonclinical studies.” These definitions were aligned with the Food and Drug Omnibus Reform Act of 2022 (FDORA), which recognizes both newer methods that do not use animals and traditional animal studies as potential sources of evidence to support initiation of studies in people.
By standardizing terminology, the FDA seeks to reduce ambiguity in regulatory expectations and to make explicit that non-animal approaches can be appropriate evidence sources for regulatory decisions when they are suitable for the product and question at hand.
The rule removes language that could be interpreted as implying that animal studies are the only acceptable approach to generate safety information for human-use products. It does not, however, prohibit animal studies nor does it change evidentiary standards for regulatory review. The FDA stated the rule will not impose new costs or requirements on drug developers.
Acting Commissioner Kyle Diamantas, J.D., explained the intent: the change is meant to allow scientists and developers greater flexibility to select the testing approach that best addresses their scientific question, supporting rigorous and modern science, including animal studies when they remain appropriate and validated alternatives when they can provide the necessary evidence.
To illustrate practical applications of non-animal methods, the FDA launched a database of New Approach Methodologies (NAMs) that contains specific use-case examples. The initial release includes 25 examples drawn from publicly available FDA review materials.
The database is intended to show how NAMs have been used in real regulatory contexts and to help developers identify appropriate methods when preparing nonclinical evidence for investigational applications and other submissions.
Developers may use NAMs to generate safety information when the methods are adequately validated and appropriate for the product and regulatory question. The agency emphasized that NAMs can better reflect human biology in some contexts and that encouraging their use complements broader HHS efforts to modernize clinical research.
The rule’s definitions follow FDORA. The FDA framed the action within Pillar 1 — Innovation and Global Leadership — of its Public Health Pillars, noting that formally recognizing a wider range of scientific approaches helps the agency keep pace with emerging technologies and strengthen regulatory science leadership.
The announcement also linked the change to HHS initiatives such as Operation TrialBlazer, which aims to modernize clinical research and accelerate development of treatments. Clearer terminology and expectations are intended to reduce avoidable uncertainty for sponsors developing nonclinical evidence and preparing applications to begin clinical trials.
The direct final rule was published simultaneously with a companion proposed rule and Federal Register notices. The FDA invited public comment from clinicians, parents, caregivers, the scientific community, industry and other stakeholders.
If the agency receives significant adverse comments on the direct final rule, it will withdraw the direct final rule and continue rulemaking through the standard notice-and-comment process using the companion proposed rule. Publishing both documents at once allows the agency to proceed efficiently under either scenario.
The FDA noted that these actions do not change regulatory evidentiary standards or create new obligations for sponsors; they clarify terminology and broaden recognition of valid scientific approaches for nonclinical evidence.
The release includes links to the Federal Register notices for the Nonclinical Testing Terminology Direct Final Rule and the companion proposed rule, the FDA’s direct final rule procedures, and other related materials. The agency also referenced a progress report titled “Reducing Animal Testing in Nonclinical Studies: Year One Progress and the Path Forward.”
The FDA provided a media contact and a general consumer contact number and encouraged stakeholders to use the formal comment processes linked in the Federal Register notices.
For clinicians, researchers and industry stakeholders, the principal takeaways are that the FDA now explicitly acknowledges nonclinical tests that do not use animals as acceptable approaches when scientifically appropriate, that practical examples of NAMs use cases are publicly available, and that the agency will accept public input during the comment period.