FDA Direct Final Rule Replaces "Animal Testing" With "Nonclinical" in Drug Development Regulations
核心洞察
The FDA issued a direct final rule replacing references to animal tests and animal studies with nonclinical tests and nonclinical studies in drug and biologic regulations.
The rule clarifies that non-animal methods such as human cells, organs-on-chips and computer models can generate safety evidence before first-in-human trials.
The FDA also launched a database with 25 examples of New Approach Methodologies drawn from publicly available agency review materials.
The U.S. Food and Drug Administration issued a direct final rule that updates its regulations to clarify that non-animal methods can be used where appropriate to test the safety of drugs and biological products intended for human use before they are tried in humans. The rule replaces terms such as "animal tests" and "animal studies" with "nonclinical tests" and "nonclinical studies," and also replaces related terms including "preclinical" and "in vitro."
The agency said the update reflects scientific and technological advances that have expanded testing options in human drug development, including methods using human cells, organs-on-chips, computer models and other advanced technologies. The rule defines "nonclinical test" and "nonclinical study" in line with the Food and Drug Omnibus Reform Act of 2022 (FDORA), which recognizes both newer methods that do not use animals and traditional animal studies as possible ways to provide the evidence needed to begin studies in people.
Regulatory Scope and Safeguards
The rule removes language that could suggest animal testing is the only acceptable way to generate safety information for regulatory decisions on products intended for human use. The FDA stated that it does not eliminate or prohibit animal studies, change evidentiary standards, or impose new costs or requirements on drug developers.
"This new rule supports the Trump Administration's push to explore ways to complement, or where appropriate, replace animal studies with methods that may better predict how medicines will actually affect people," said Acting FDA Commissioner Kyle Diamantas, J.D. "It gives scientists and drug developers greater flexibility to use the testing approach that best addresses their scientific question. 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."
The changes cover key stages of drug development that occur before a drug can move into human clinical trials and marketing. Traditionally, the testing required to demonstrate safety and efficacy at these stages has involved extensive animal testing. The FDA said advances in human-based technologies now make it possible to avoid animal testing while better predicting drug effects in humans, and that clearer terminology and regulatory expectations can reduce avoidable uncertainty as sponsors develop nonclinical evidence and prepare applications to begin clinical trials.
New Approach Methodologies Database
Alongside the rule, the FDA launched a database featuring specific uses of New Approach Methodologies (NAMs). The initial release includes 25 examples drawn from publicly available FDA review materials. Developers may use NAMs to generate safety information when the methods are adequately validated and appropriate for the product and regulatory question.
The agency framed the actions as part of Pillar 1, Innovation and Global Leadership, of its Public Health Pillars, and said encouraging NAM use complements Operation TrialBlazer, the Department of Health and Human Services (搜索) initiative to modernize clinical research and accelerate development of life-saving treatments.
Comment Period and Rulemaking Mechanics
The FDA is inviting the public, including clinicians, parents, caregivers, the scientific community, industry and others, to comment on the rule. The agency published the direct final rule together with a companion proposed rule and a comment period. If it receives significant adverse comments on the direct final rule, the agency will withdraw it and continue rulemaking through the standard notice-and-comment process using the companion proposed rule. Publishing both simultaneously ensures the rulemaking can proceed efficiently under either scenario.
Advocacy Group Calls for Further Reform
The Physicians Committee for Responsible Medicine, which said it has advocated for the reform for nearly a decade, welcomed the change. In 2017, Physicians Committee experts identified 235 FDA regulations that should be updated to remove barriers to nonanimal methods and submitted the findings to the agency.
"Changing a few words in federal regulations can have a significant impact," said Janine McCarthy, MPH, director of research policy for the Physicians Committee. "For decades, the FDA's regulations have directed drug developers toward animal tests, even as more predictive human-based methods have become available. Today's action sends a clear message that nonanimal methods should play a central role in evaluating the safety of new medicines."
The update builds on the FDA Modernization Act 2.0, which removed a longstanding statutory preference for animal testing, and advances the goals of the FDA Modernization Act 3.0, separate versions of which have passed both chambers of Congress, which would mandate the FDA to update its regulations accordingly.
The Physicians Committee said additional reforms are still needed. The update covers only a subset of the regulations required to comprehensively modernize the drug testing framework. It leaves out the Animal Rule, which provides a pathway for approving certain medical countermeasures based solely on animal testing, as well as provisions affecting product classification requests and orphan drug designation, which the organization said are needed to replace animal testing earlier in a product's regulatory pathway.