The Priority Review

Regulation

FDA rewrites drug safety rules to say “nonclinical,” not “animal,” testing

A direct final rule takes effect February 4, 2027, unless the agency receives significant adverse comments by December 7, 2026.

By The Priority Review desk

Machine-summarized from the primary sources listed below; not independently reported. How we use automation

The U.S. Food and Drug Administration on September 21 announced a direct final rule that changes how its drug and biologics regulations describe the safety testing done before a product is first given to people. The rule and a companion proposed rule were published in the Federal Register on September 22, under docket FDA-2026-N-5347.

What changes

According to the Federal Register notice, the rule:

  • replaces references to “animal” tests or studies with “nonclinical” tests or studies;
  • adds definitions of “nonclinical test” and “nonclinical study,” which the FDA says follow the Food and Drug Omnibus Reform Act of 2022 (FDORA);
  • replaces “preclinical” and “in vitro” with “nonclinical” for consistent terms.

The amendments touch Title 21 of the Code of Federal Regulations, parts 312, 314, 315, 361 and 601.

What does not change

The FDA says the rule does not eliminate or prohibit animal studies, does not change evidentiary standards, and does not impose new costs or requirements on drug developers. The Federal Register notice says the rule “adds no new requirements.” Its stated purpose is to remove language that could suggest animal testing is the only acceptable way to generate safety information.

The FDA also launched a database of specific uses of New Approach Methodologies (NAMs), such as methods using human cells, organs-on-chips and computer models. The first release holds 25 examples drawn from publicly available FDA review materials. The agency says developers may use NAMs when the methods are adequately validated and suit the product and the regulatory question.

Why it matters for trial sponsors

The FDA links the change to Operation TrialBlazer, the Department of Health and Human Services initiative to modernize clinical research. The agency says clearer terms can reduce avoidable uncertainty as sponsors prepare applications to begin clinical trials.

Dates to watch

  • Comments on the direct final rule or the companion proposed rule are due by December 7, 2026.
  • If the FDA receives no significant adverse comments, it intends to confirm the February 4, 2027, effective date within 30 days after the comment period ends.
  • If it receives significant adverse comments, it will withdraw the direct final rule and continue through the proposed rule.

Sources