FDA Proposes To Strike The Words Animal Test From Its Drug Rules, And Prices The Change At Zero

The Food and Drug Administration published two notices in the Federal Register on 22 September 2026 that remove the terms "animal test", "animal study", "preclinical test" and "in vitro test" from 38 provisions of its drug and biologics regulations and put "nonclinical test" or "nonclinical study" in their place. The amendments reach five parts of Title 21 of the Code of Federal Regulations, covering the investigational new drug application, new drug approvals, diagnostic radiopharmaceuticals, drugs used in research and licensing. Eighteen of the amended provisions sit in part 312, twelve in part 314, three in part 315, one in part 361 and four in part 601.

The machinery matters more than the vocabulary. The first notice is a direct final rule; the second is a companion proposed rule carrying the same amendments, published as the fallback if the first is withdrawn. Both run under RIN 0910-AJ27 and Docket No. FDA-2026-N-5347. The direct final rule states an effective date of 4 February 2027, and comments on either notice close on 7 December 2026, a 75-day period, with comments filed against the proposed rule counting against the direct final rule as well.

That effective date is conditional. If FDA receives no significant adverse comment, it will publish a document confirming the date within 30 days of the comment period closing. If it receives one, it will publish a withdrawal of the direct final rule within 30 days and start again under the proposed rule by ordinary notice and comment. The agency reserves the right to sever, so a comment aimed at one part need not take down the rest. The procedure follows FDA's own 1997 direct final rulemaking document at 62 FR 62466, and is reserved for changes nobody is expected to contest.

The agency prices the change at nothing

The economic analysis states plainly what this rule is. Estimated annualised benefits are $0 million per year at either a 3 or a 7 percent discount rate. Costs are the same figure at either rate, over a 10-year horizon, in millions of 2025 dollars.

"This rule imposes no new requirements on industry and so is expected to generate no costs."
— FDA, direct final rule, Executive Summary

FDA writes that it "already permits the use of nonanimal studies and this rule will not preclude sponsors from using any types of studies that are currently permitted; industry will continue to provide information on the nonanimal studies that they use and rely on." On the provisions that previously paired the words "animal" and "in vitro", the notice states that sponsors have already been submitting in silico and in chemico data under them, and that FDA has already accepted such data where appropriate, because those provisions turn on whether information is significant or relevant to human safety rather than on the method that produced it.

So nothing becomes admissible on 4 February 2027 that was inadmissible on 21 September 2026, and nothing becomes mandatory either. Every one of the 38 provisions is described as imposing no new testing requirement. This is a rewrite of vocabulary, and the agency says so in as many words.

Two things that do move

The first is the definition itself, added at 21 CFR 312.3(b) and, for studies alone, at 21 CFR 314.3, 315.2 and 601.31.

"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. Such test or study may include the following: (1) Cell-based assays. (2) Organ chips and microphysiological systems. (3) Computer modeling. (4) Other nonhuman or human biology-based test methods, such as bioprinting. (5) Animal tests or studies."
— the definition added to 21 CFR 312.3(b), direct final rule

Organ chips, microphysiological systems and computer modeling now appear by name in the text of the CFR, where the regulation previously named only animals and in vitro work. The wording is adapted from section 505(z) of the Federal Food, Drug, and Cosmetic Act, added by the Food and Drug Omnibus Reform Act of 2022. FDA widened it twice over, adding "study" alongside "test" because parts 314, 315 and 601 speak of studies, and dropping the statutory clause confining such a test to the period before or during clinical trials.

The second is one provision. At 21 CFR 312.23(a)(3)(iv)(f), FDA states that replacing "animals" with "nonclinical studies" expands the types of studies that may supply the basis for identifying risks of particular severity in a general investigational plan, while imposing no requirement to run additional tests. At 21 CFR 312.32(c)(1)(iii) the paragraph heading "Findings from animal or in vitro testing" becomes nonclinical, which places a finding from a computer model or an organ chip unambiguously inside the 15-day safety report. FDA presents that as clarifying a longstanding position rather than creating a duty.

Two registers that do not match

Against all of this sits the agency's own announcement of 10 April 2025, headlined as a plan to phase out the animal testing requirement for monoclonal antibodies and other drugs.

"This initiative marks a paradigm shift in drug evaluation and holds promise to accelerate cures and meaningful treatments for Americans while reducing animal use."
— Martin A. Makary, FDA Commissioner, 10 April 2025

These two September notices describe the same programme in the opposite key: noncontroversial, no new requirements, no costs, and, in the agency's phrase, "not expected to affect industry practice". Whoever expected the roadmap to arrive as regulation should read the pricing. Animal testing is not restricted here. Animal tests and studies are the fifth item in the new definition of a nonclinical test. The Animal Rule, at 21 CFR part 314 subpart I and part 601 subpart H, is excluded outright, as is part 316, the orphan-drug regulations, under which supporting animal studies remain limited to preclinical efficacy work in an animal model.

What the record does not carry

No significant adverse comment is reported here. The docket closes on 7 December 2026, and the February date holds only if none arrives. Nothing on the record says whether the monoclonal antibody pilot programme announced in April 2025 was launched, who joined it, or what it found. Neither notice gives a figure for the number of animals used annually in FDA-regulated drug safety testing, or for how far that number should fall. No specific new approach methodology is named as formally qualified for a safety use through the Drug Development Tools or ISTAND programmes, which the notices name as the route. FDA says sponsors have filed data from these methods and that it has accepted it, but gives no count. The draft guidance published in March 2026 is not recorded as finalised. And no party outside FDA is on the record here: no industry group, no patient organisation, no animal welfare body.