FDA drafts guidance on animal testing alternatives
The US Food and Drug Administration (FDA) has released draft guidance aimed at assisting pharmaceutical manufacturers in transitioning from animal studies to non-animal alternatives for drug development. The agency is urging companies to adopt new approach methodologies (NAMs), incorporating in vitro human-based systems, such as organs-on-chips and in silico modeling, to assess drug safety.FDA announced that the guidance “marks a major milestone in the implementation of the FDA roadmap to reducing animal testing and reflects the FDA's commitment to moving away from using animal testing as the default method for gaining drug safety information.”
"Technological advances are allowing us to move beyond animal testing in drug development, which has a poor track record of predicting safety and efficacy in humans," said FDA Commissioner Marty Makary. "This guidance will facilitate the adoption of modern alternatives to animal testing in regulatory submissions."
Efforts to eliminate animal testing have been underway for some time. In December 2022, Congress passed the FDA Modernization Act 2.0 that confirms non-animal alternatives can be used to support an Investigational New Drug (IND) application or a biosimilar biologics license application (BLA) instead of conducting animal studies.
Following up on this legislation, in April 2025 FDA announced a plan to phase out animal testing by implementing NAMs to evaluate drug safety. (RELATED: FDA seeks to reduce animal testing requirements for mAbs, other drugs, Regulatory Focus 11 April 2025)
Then in December 2025, FDA announced that it would reduce the use of monkeys for safety testing of monoclonal antibodies. (RELATED: FDA guidance would cut back on using monkeys for safety testing of monoclonal antibodies, Regulatory Docus, 2 December 2025)
This draft guidance establishes four core principles for using NAMs: context of use (COU), human biological relevance, technical characterization, and fit-for-purpose.
The guidance states that the COU should clearly outline the intended use and regulatory purpose of the NAM to address a specific drug development decision context. An adequate COU must address a data gap and fulfill one or more objectives related to drug development.
Human biological relevance of a NAM refers to the connection between the data generated from the NAM and its potential impact on assessing the drug's effects in the context of human testing. This includes predicting toxicities that cannot be measured during clinical trials.
The technical characterization of a NAM is crucial for establishing scientific confidence in the data generated using this platform. It ensures that the method is robust, reliable, and reproducible enough to accurately quantify specific endpoints.
A NAM is considered fit for purpose if it helps FDA’s Center for Drug Evaluation and Research (CDER) in making regulatory decisions. For example, this method could be used to fill a data gap or provide additional safety information on drugs when traditional nonclinical models are unavailable. The guidance states that “an in vitro NAM might help to understand a mechanism of toxicity or mechanism of action seen in humans which cannot be modeled in animals due to species-specific differences.”
The FDA encourages sponsors to reach out to the relevant review division if there is any uncertainty regarding the suitability of a non-animal testing method.
FDA is accepting comments on the draft guidance on www.regulations.gov under docket number FDA-2025-D-6131 through 19 May.
Draft guidance; Announcement
×
Welcome to the new RAPS Digital Experience
We have completed our migration to a new platform and are pleased to introduce the updated site.
What to expect: If you have an existing login, please RESET YOUR PASSWORD before signing in. After you log in for the first time, you will be prompted to confirm your profile preferences, which will be used to personalize content.
We encourage you to explore the new website and visit your updated My RAPS page. If you need assistance, please review our FAQ page.
We welcome your feedback. Please let us know how we can continue to improve your experience.