The U.S. Food and Drug Administration (FDA) has updated its regulations to formally recognize the use of non-animal testing methods in the development of drugs and biological products, expanding opportunities for human-relevant technologies such as organ-on-a-chip systems, human cell-based models, and computational approaches.
Announced on September 21, 2026, the FDA issued a direct final rule clarifying that non-animal methods may be used, when appropriate, to generate safety evidence before investigational therapies are tested in humans. The regulatory change is intended to provide drug developers with greater flexibility while maintaining existing standards for safety and scientific evidence.
From “Animal Studies” to “Nonclinical Studies”
A central part of the regulatory update is a change in terminology.
The FDA is replacing terms including “animal tests” and “animal studies” with broader terms such as “nonclinical tests” and “nonclinical studies.” Related terminology, including “preclinical” and “in vitro,” is also being revised.
The definitions align FDA regulations with the Food and Drug Omnibus Reform Act of 2022 (FDORA), which recognizes both traditional animal studies and newer non-animal approaches as potential sources of evidence supporting the transition of investigational drugs into human studies.
Importantly, the new rule does not prohibit animal studies or change the evidentiary standards required of drug developers. Instead, it removes regulatory language that could imply animal testing is the only acceptable method for generating safety information.
Human Cells, Organs-on-Chips and Computer Models
Advances in biomedical science have created new ways of assessing the safety and biological effects of potential therapies without relying exclusively on conventional animal models.
The FDA specifically highlighted approaches involving human cells, organs-on-chips, computer models and other advanced technologies. These approaches form part of a broader category known as New Approach Methodologies (NAMs).
NAMs may be used to generate safety information when they are adequately validated and appropriate for the particular product and regulatory question. The FDA has emphasized that the goal is not to substitute one mandatory testing framework for another, but to allow scientists to select methods suited to the scientific question being addressed.
Acting FDA Commissioner Kyle Diamantas, JD, said:
“It gives scientists and drug developers greater flexibility to use the testing approach that best addresses their scientific question.”
He emphasized that the agency intends to support rigorous science that can include animal studies when appropriate as well as validated alternatives capable of providing the evidence needed to protect patients.
FDA Launches Database of New Approach Methodologies
Alongside the regulatory change, the FDA launched a new database showing how New Approach Methodologies have already been applied in regulatory settings.
The initial database contains 25 examples drawn from publicly available FDA review materials, providing developers with practical examples of circumstances in which alternative methodologies have been used.
The database is intended to provide greater regulatory clarity as researchers and pharmaceutical developers consider incorporating NAMs into drug development programs.
What Could This Mean for Cancer Drug Development?
The regulatory shift could be particularly relevant to oncology, where increasingly complex therapeutic approaches, including targeted therapies, monoclonal antibodies and other biologic medicines, require models capable of capturing human-specific biology.
Human cell-based systems, organ-on-a-chip platforms and computational models could potentially complement conventional animal studies during nonclinical development, particularly where validated methods can provide information that is more directly relevant to human biology.
However, the FDA’s action does not mean that animal testing will immediately disappear from cancer drug development. The appropriate testing strategy will continue to depend on the investigational therapy, available scientific evidence, validation of alternative methods and the specific regulatory question being addressed.
A Living Library of Cancer: New Models Could Help Researchers Find Better Treatments
Part of a Broader FDA Shift Toward Modern Drug Development
The rule is part of a broader FDA and U.S. Department of Health and Human Services effort to modernize drug development.
The agency said expanding the use of NAMs aligns with its Innovation and Global Leadership public health pillar and complements Operation TrialBlazer, an HHS initiative focused on modernizing clinical research and accelerating the development of new treatments.
By clarifying regulatory terminology and expectations, the FDA aims to reduce uncertainty for sponsors as they generate nonclinical evidence and prepare applications to begin human clinical trials.
The FDA is now inviting comments from clinicians, researchers, patients, caregivers, industry representatives and other members of the public.
Because the regulation was issued as a direct final rule alongside a companion proposed rule, the FDA said it may withdraw the direct final rule if significant adverse comments are received and proceed through the standard notice-and-comment rulemaking process instead.
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