The U.S. Food and Drug Administration (FDA) has issued a direct final rule that updates agency regulations to clarify that non-animal methods can be used where appropriate for testing the safety of drugs and biological products intended for human use. The update reflects scientific and technological advances that have expanded the range of testing options available in human drug development, including methods using human cells, organs-on-chips, computer models, and other advanced technologies.
The rule replaces specific terms such as "animal tests" and "animal studies" with the terms "nonclinical tests" and "nonclinical studies." Related terms, including "preclinical" and "in vitro," are also replaced. The rule defines these new terms in line with the Food and Drug Omnibus Reform Act of 2022 (FDORA), which recognizes newer methods that do not use animals alongside traditional animal studies as possible ways to provide evidence needed to begin studies in people.
The rule removes language that could suggest animal testing is the only acceptable way to generate safety information for regulatory decisions in products intended for human use. However, the agency notes that it does not eliminate or prohibit animal studies, change evidentiary standards, or impose new costs or requirements on drug developers. Developers may use New Approach Methodologies (NAMs)—innovative testing methods that may better reflect human biology—when the methods are adequately validated and appropriate for the product and regulatory question.
To demonstrate the practical application of these methods, the FDA also launched a database featuring specific uses of NAMs. The initial release includes 25 examples drawn from publicly available FDA review materials. The agency is inviting the public, including clinicians, parents, caregivers, the scientific community, industry, and others, to comment on the rule. If the FDA receives significant adverse comments on the direct final rule, the agency will withdraw it and continue rulemaking through the standard notice-and-comment process using a companion proposed rule.
