FDA Rule Clarifies Use of Non-Animal Methods for Drug Safety Testing

The FDA issued a direct final rule updating regulations to clarify that non-animal methods may be used, where appropriate, to evaluate the safety of human drugs and biological products before clinical trials. These approaches include human-cell systems, organs-on-chips and computer models. The changes align regulatory terminology with the Food and Drug Omnibus Reform Act of 2022.

The rule replaces terms such as “animal tests” and “animal studies” with “nonclinical tests” and “nonclinical studies,” removing wording that could imply animal testing is the only acceptable source of safety evidence. It does not eliminate or prohibit animal studies, change evidentiary standards, or impose new costs or requirements on developers. The FDA also launched a New Approach Methodologies database containing 25 examples drawn from publicly available agency review materials.

For clinical researchers and drug developers, the update clarifies that alternative methods can support safety assessments when adequately validated and appropriate to the product and regulatory question. The announcement does not establish that these methods universally outperform animal studies. The FDA is seeking public comments; if it receives significant adverse comments, it will withdraw the direct final rule and proceed through standard notice-and-comment rulemaking using a companion proposed rule.