FDA Updates Nonclinical Testing Terminology in Drug Regulations
A direct final rule replaces animal-focused wording in selected drug and biologic regulations with broader nonclinical terminology. It is scheduled to take effect on 4 February 2027, subject to the direct-final-rule process.
- Issuing Authority
- Food and Drug Administration
- Jurisdiction
- United States
- Document Covered
- Nonclinical Testing Terminology, direct final rule, 91 FR 59988; published 22 September 2026; scheduled effective 4 February 2027 subject to the stated rulemaking process.
A Broader Definition in Existing Regulations
FDA published its Nonclinical Testing Terminology direct final rule on 22 September 2026. The rule updates selected provisions governing human drugs and biological products so that their wording accommodates scientifically valid non-animal methods. It follows statutory changes made through the Food and Drug Omnibus Reform Act of 2022 and aligns regulatory language with the wider range of evidence already used in drug development.
The amendments affect parts 312, 314, 315, 361 and 601 of Title 21 of the Code of Federal Regulations. They replace specified references to animal tests or studies with nonclinical tests or studies and make corresponding changes to some uses of preclinical and in vitro. This gives developers a common term for evidence generated through different experimental and computational approaches.
What Nonclinical Testing Includes
The definitions cover in vitro, in silico and in chemico tests or studies, as well as nonhuman in vivo work. Listed examples include cell-based assays, organ chips and microphysiological systems, computer modeling, other human- or nonhuman-biology-based methods such as bioprinting, and animal studies. The examples are illustrative, allowing the definition to accommodate further scientifically valid approaches.
The regulatory definitions focus on the type of evidence. FDA omitted the statutory wording about tests occurring before or during a clinical trial because the provisions being amended address data requirements at different points in development and reporting. The term nonclinical therefore describes the evidence category without imposing a single development-stage cutoff.
How the IND Provisions Change
One important amendment concerns section 312.23(a)(8), which describes pharmacology and toxicology information in an investigational new drug (IND) application. The revised wording calls for adequate nonclinical information supporting the proposed clinical investigation. The nature, duration and scope of testing remain linked to the clinical study being proposed.
The provision continues to address pharmacological effects, mechanisms of action and available information on absorption, distribution, metabolism and excretion. Toxicology information includes an integrated summary and detailed data tables for studies primarily supporting clinical safety. Related changes extend the same terminology to investigator brochures, safety reports and annual reporting.
Scope and Implementation
FDA states that the rule adds no new testing requirements. Developers remain responsible for providing evidence adequate to support human safety, and FDA will assess that evidence in the context of the development program. Existing animal-testing options remain within the new definition alongside non-animal approaches.
The change is limited to the specified provisions. The Animal Rule, orphan-drug designation regulations and the separate definition of nonclinical laboratory study under the good laboratory practice regulations are outside its scope. These boundaries are particularly relevant when deciding which regulatory provisions apply to a proposed NAM.
A Scheduled Effective Date
The rule is scheduled to become effective on 4 February 2027. FDA set a comment deadline of 7 December 2026 and published a companion proposed rule. Significant adverse comments can lead to withdrawal of the direct final rule, with the comments then considered through the ordinary rulemaking process.
If FDA receives no significant adverse comments, it intends to publish confirmation of the effective date within 30 days after the comment period closes. For drug developers, the immediate development is a published terminology change with a defined implementation process; its scheduled effective date and the adequacy of each nonclinical evidence package remain separate considerations.