The U.S. Food and Drug Administration has updated its regulations to make clear that drug and biological product developers can use non-animal testing methods when appropriate to evaluate safety before products are tested in humans.

The direct final rule reflects advances in scientific and technological methods available for human drug development, including testing involving human cells, organs-on-chips, computer models and other emerging technologies, a news release from the agency said.

“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 Acting FDA Commissioner of Food and Drugs Kyle Diamantas, J.D. in the release. “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.”

Under the updated regulations, terms such as “animal tests” and “animal studies” will be replaced with “nonclinical tests” and “nonclinical studies.” Related terminology, including “preclinical” and “in vitro,” also is being replaced.

The rule defines “nonclinical test” and “nonclinical study” in accordance with the Food and Drug Omnibus Reform Act of 2022, or FDORA. The law recognizes both newer methods that do not use animals and traditional animal studies as potential ways to generate evidence needed before human studies begin.

The FDA said the changes remove language that could imply animal testing is the only acceptable method for producing safety information used in regulatory decisions involving products intended for human use.

The rule does not eliminate or prohibit animal studies. It also does not change existing evidentiary standards or impose new costs or requirements on drug developers.

Alongside the regulatory update, the FDA launched a database showing specific applications of New Approach Methodologies, known as NAMs. The initial database includes 25 examples drawn from publicly available FDA review materials.

NAMs are innovative testing approaches that may better reflect human biology. Drug developers may use the methods to generate safety information when they have been adequately validated and are appropriate for the product and the regulatory question being addressed.

The new rule and database are part of several actions being taken by the Department of Health and Human Services, including the FDA, to advance drug development using NAMs.

The actions also align with Pillar 1, Innovation and Global Leadership, of the FDA’s Public Health Pillars, the release said. The agency said formally recognizing a broader range of scientific approaches will allow its regulatory framework to keep pace with emerging technologies while supporting its role in regulatory science.

The FDA said encouraging the use of NAMs also complements Operation TrialBlazer, an HHS initiative focused on modernizing clinical research and accelerating the development of life-saving treatments.

The agency said clearer terminology and regulatory expectations could reduce avoidable uncertainty for sponsors as they develop nonclinical evidence and prepare applications to begin clinical trials.

The FDA is seeking public comments on the rule from clinicians, parents, caregivers, members of the scientific community, industry representatives and others.

Additional information is available through the Federal Register notices announcing the direct final rule, the companion proposed rule and the comment period.

The FDA said it will withdraw the direct final rule if it receives significant adverse comments and continue the rulemaking process through the standard notice-and-comment procedure using the companion proposed rule. The agency published both rules at the same time so the rulemaking process can proceed efficiently under either scenario.