The Food and Drug Administration issued a direct final rule Monday that would replace “animal tests” and “animal studies” with “nonclinical tests” and “nonclinical studies” in its human-drug regulations. The rule itself says it “adds no new requirements”; FDA’s release says it “does not eliminate or prohibit animal studies.” It takes effect Feb. 4, 2027 unless FDA withdraws it, and was filed for public inspection Monday for publication in the Federal Register on Tuesday, Sept. 22.
What the rule changes
The rule, titled “Nonclinical Testing Terminology,” amends parts 312, 314, 315, 361 and 601 of the Code of Federal Regulations. It covers only human drugs and biological products. The rule says the amendments “are intended to remove an emphasis, in certain places, on the use of animal testing as the only scientific methodology to assess the safety of a drug in the nonclinical setting.”
It also adds a definition. The rule adds this definition to section 312.3(b): “Nonclinical test and nonclinical study mean a test or study conducted in vitro, in silico, or in chemico, or a nonhuman in vivo test or study.” Its examples are cell-based assays; organ chips and microphysiological systems; computer modeling; other nonhuman or human biology-based test methods, such as bioprinting; and “Animal tests or studies.”
The concrete edits are substitutions, and the rule also replaces “preclinical” and “in vitro” with “nonclinical.” Section 312.88’s “review of animal studies prior to initial human testing” becomes a review of nonclinical studies. In 314.50(d)(2), “animal and in vitro studies with drug” becomes “nonclinical studies with the drug.”
Background: the 2022 law
The rule says section 3209 of the Food and Drug Omnibus Reform Act of 2022 replaced “preclinical tests (including tests on animals)” in the federal drug law with “nonclinical tests,” and that the rule “aligns” FDA’s regulations with that change. The rule cites Public Law 117-328, the Consolidated Appropriations Act, 2023, and gives the year 2022 but no enactment day.
What it does not do
It excludes the “Animal Rule,” which sits in subparts of parts 314 and 601 and is the rule for efficacy data “from studies conducted in carefully vetted animal models” under narrow conditions; part 316 on orphan drugs; and part 58 on nonclinical laboratory studies. The rule also says “there remain areas where animal testing is important and necessary.”
What FDA says it expects
In the rule, FDA says it is “optimistic” that scientifically valid new methods will lead to “a reduced need for animal testing.” FDA expects “an incremental shift by some sponsors from animal testing to other types of nonclinical testing, when appropriate.” The rule’s own tables list its quantified costs and benefits as $0, and FDA says it does not expect to be able to quantify the benefits.
How a direct final rule works, and the dates
FDA used the direct route because it believes the changes are “noncontroversial changes in terminology that are not expected to affect industry practice.” Comments are due Dec. 7, 2026, at regulations.gov under docket FDA-2026-N-5347. The rule is scheduled for publication Tuesday, Sept. 22, and takes effect Feb. 4, 2027 unless withdrawn.
If FDA receives no significant adverse comments, it “intends to publish a document confirming the effective date” in the Federal Register within 30 days after the comment period ends. If it receives timely significant adverse comments, FDA says it will publish a withdrawal within 30 days after the comment period ends, and the companion proposed rule “provides a procedural framework within which the rule may be finalized.”
FDA’s press release and database
FDA’s release is headlined “FDA Updates Regulations to Advance Innovative Alternatives to Animal Testing”; the rule text itself is a terminology change.
In FDA’s release, Acting FDA Commissioner of Food and Drugs Kyle Diamantas said: “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.”
FDA says it also launched a database of uses of new approach methodologies, with an initial 25 examples from public FDA review materials. The page says it “is not an exhaustive list, does not constitute FDA guidance or approval of a method for any other use, and should not be interpreted as a recommendation that a particular method will be acceptable in a future submission”.
What FDA’s year-one report says
FDA’s April 2026 year-one report on reducing animal testing, which calls itself “an accountability document,” grades FDA’s own progress; it says “validated alternatives exist for some endpoints (skin sensitization, mutagenic impurities) but not others (developmental toxicity, chronic toxicity).”
What we could not check
On Monday, the two Federal Register documents we read — the direct final rule and its companion proposed rule — are public-inspection copies; the Federal Register page says “This document is unpublished.” The regulations.gov docket returned an access error, so we have no comment count. We read the 2022 law only as the rule describes it. We found no reaction from an independent outlet, advocacy group or lawmaker in the pages we opened.
Sources and further reading
- FDA Updates Regulations to Advance Innovative Alternatives to Animal Testing
- Nonclinical Testing Terminology (direct final rule), document 2026-19350
- Nonclinical Testing Terminology (companion proposed rule), document 2026-19349
- New Approach Methodologies (NAMs) Database of Use Case Examples
- Reducing Animal Testing in Nonclinical Studies: Year One Progress and the Path Forward (April 2026)