Author: Site Editor Publish Time: 2026-10-12 Origin: Site
The U.S. Food and Drug Administration (FDA) has published a direct final rule titled Nonclinical Testing Terminology in the Federal Register, updating terminology across selected regulations governing the safety assessment and reporting of human drugs and biological products. Published on September 22, 2026, the rule replaces certain references to “animal tests” and “animal studies” with the broader terms “nonclinical tests” and “nonclinical studies,” reflecting the growing role of scientifically valid New Approach Methodologies (NAMs) in drug development.
The rule is scheduled to take effect on February 4, 2027, subject to FDA’s direct final rulemaking procedures. The public comment deadline is December 7, 2026.
The FDA’s regulatory update aims to remove terminology that may imply animal testing is the only scientific approach available for nonclinical safety assessment. It establishes broader definitions of nonclinical testing and aligns terminology across selected provisions of the agency’s regulations.
The amendments cover specified provisions of Title 21 of the Code of Federal Regulations, including Parts 312, 314, 315, 361 and 601, which address aspects of investigational drug development, drug safety and reporting, and biological products.
Under the updated terminology, nonclinical testing may encompass a wider range of scientifically valid methods, including:
Human cell-based in vitro models: Laboratory systems using human-derived cells to investigate biological responses and potential safety risks.
Organ-on-a-chip and microphysiological systems: Models designed to reproduce selected functions of human organs or tissues.
Computational modeling: In silico approaches that use computational methods to evaluate biological processes, drug effects or potential toxicological risks.
Other biology-based testing methods: Emerging approaches, including bioprinting and other relevant experimental systems.
Animal studies: Existing animal-based methods remain within the scope of nonclinical testing.
The central change is the recognition of a broader range of nonclinical methodologies in regulatory terminology, rather than a mandate to replace one testing method with another.
No. The FDA’s rule does not prohibit animal studies, lower existing safety evidence standards or introduce new regulatory requirements.
Animal testing remains an available option in drug development. Alternative methods may be considered when they are scientifically valid and suitable for addressing the specific safety questions relevant to a drug candidate or biological product.
The regulatory significance of this change lies in the flexibility to consider different sources of nonclinical evidence. The scientific relevance, reliability and applicability of the evidence remain central to determining whether a particular method is appropriate for its intended regulatory purpose.
For pharmaceutical developers, the update should therefore be understood as a terminology and regulatory alignment measure that supports broader consideration of nonclinical approaches—not as an automatic exemption from established safety assessment requirements.
New Approach Methodologies (NAMs) encompass emerging and alternative approaches used to investigate biological mechanisms, predict human responses and assess potential safety risks. Depending on the technology and its intended application, NAMs may provide information that complements existing nonclinical studies or, where scientifically justified and accepted by the relevant regulator, supports alternative approaches to specific assessment questions.
Their potential value extends beyond reducing animal use. Human-relevant models may help researchers investigate biological responses that are difficult to characterize using conventional models alone. Computational approaches can also support the integration of experimental findings, mechanistic information and other relevant datasets.
However, the regulatory applicability of a NAM depends on more than the novelty of the technology. Important considerations include:
Scientific validation: Whether the method has adequate evidence supporting its reliability and reproducibility.
Context of use: Whether the method is appropriate for the specific biological endpoint, drug type, development stage and regulatory question.
Human relevance: Whether the model or approach meaningfully represents the biological processes relevant to the intended assessment.
Data quality and interpretation: Whether the resulting evidence is sufficiently robust to support scientifically justified conclusions.
Regulatory engagement: Whether early discussions with the relevant authority can clarify expectations for study design, data interpretation and submission.
NAMs should therefore be viewed as part of an evolving evidence framework. Their value depends on the quality of the method and its suitability for the specific scientific and regulatory purpose.
The FDA’s terminology update forms part of a broader movement toward evaluating nonclinical evidence according to scientific relevance and the intended regulatory application.
In September 2026, the European Medicines Agency (EMA) launched a voluntary data submission pilot for NAMs. The initiative allows eligible stakeholders—including pharmaceutical companies, method developers, contract research organizations and academic laboratories—to submit and discuss NAMs data outside marketing authorization applications.
The EMA pilot aims to increase regulatory experience with NAMs, facilitate scientific dialogue, encourage international harmonization and support the development of a sustainable framework for incorporating these methods into medicines regulation.
Although the FDA rule and EMA pilot are distinct initiatives, both highlight the importance of generating relevant data and building regulatory understanding of emerging nonclinical approaches.
For companies developing products for international markets, these developments reinforce the need to consider the intended use of a testing method, the strength of its supporting evidence and the expectations of the relevant regulatory authority.
For pharmaceutical companies, the expanding role of NAMs creates opportunities to reassess how nonclinical evidence is generated and integrated throughout drug development.
First, R&D teams may benefit from evaluating whether human-relevant models or computational methods can address specific uncertainties earlier in development. When scientifically appropriate, these approaches may complement conventional studies and help prioritize further investigation.
Second, nonclinical development strategies should be designed around defined safety questions rather than the assumption that a single testing approach will be suitable for every product. This requires coordination among pharmacology, toxicology, analytical science, computational modeling and regulatory affairs teams.
Third, companies should distinguish between the scientific promise of an emerging method and its acceptance for a particular regulatory purpose. Early engagement with regulators and careful documentation of a method’s validation, limitations and context of use can help clarify its potential role in a development program.
For API and finished pharmaceutical product manufacturers, NAMs may also be relevant to the broader development ecosystem, particularly where new technologies can contribute to mechanistic understanding, early-stage risk assessment or the evaluation of drug-related biological responses. Their application to a specific product or regulatory submission must nevertheless be assessed on a case-by-case basis.
At LONCOM, we view the development of NAMs as part of a broader evolution in pharmaceutical R&D and regulatory science. The key question is not simply whether one testing technology can replace another, but which combination of evidence can most reliably address the scientific questions that matter for human safety.
As nonclinical research continues to evolve, pharmaceutical developers will need to integrate experimental models, analytical technologies, computational approaches, data science and regulatory expertise into coherent development strategies.
For companies pursuing international development and market access, this means keeping pace with regulatory developments while maintaining a disciplined focus on scientific validity, evidence quality and product-specific requirements.
As the FDA, EMA and other regulatory authorities continue to build experience with NAMs, the industry should monitor emerging guidance, regulatory precedents and opportunities for scientific engagement. The long-term opportunity lies in developing fit-for-purpose evidence strategies that are scientifically robust, context-specific and aligned with applicable regulatory expectations.
LONCOM will continue to monitor international pharmaceutical regulatory developments and their implications for drug development, nonclinical research and global market access.
1. FDA — Nonclinical Testing Terminology, Direct Final Rule Read the official Federal Register rule.
2. FDA — Nonclinical Testing Terminology, Companion Proposed Rule Read the companion proposed rule.
3. EMA — New approach methodologies to replace and reduce animal testing: Voluntary data submission pilot Read the EMA pilot overview.
