FDA phasing out animal testing in preclinical safety studies

The Food and Drug Administration (FDA) said it will reduce or replace its animal testing requirement for “more effective, human-relevant methods,” such as artificial intelligence (AI)-based computational models and new approach methodologies (NAMs). The FDA will work with other agencies, such as the National Institutes of Health, to accelerate the validation and adoption of these new, innovative methods through the Interagency Coordinating Committee on the Validation of Alternative Methods.

The change will take effect immediately for investigational new drug (IND) applications where NAMs data is encouraged. The agency also planned to begin using pre-existing, real-world safety data from other countries with comparable regulatory standards.

“This initiative marks a paradigm shift in drug evaluation and holds promise to accelerate cures and meaningful treatments for Americans while reducing animal use. By leveraging AI-based computational modeling, human organ model-based lab testing, and real-world human data, we can get safer treatments to patients faster and more reliably, while also reducing (research and development) costs and drug prices,” said FDA Commissioner Dr. Martin Makary in an April 10 press release.

FDA Modernization Act 2.0 and pilot program

In its effort to reduce animal testing in preclinical safety studies, the agency seeks to move toward NAMs such as computational modeling, advanced in vitro assays, and organ-on-a-chip systems, according to the FDA roadmap outlining its approach.

The 11-page roadmap cites the FDA Modernization Act 2.0 that Congress passed in 2022, clarifying that data from the use of certain alternatives to animal testing can be used in new drug applications to the agency. The FDA Modernization Act 2.0 did not change the regulatory process for drugs, medical devices, and treatments prior to reaching clinical trials in humans, nor did it eliminate the need for animal testing in those areas.

To start, the new initiative has identified monoclonal antibodies (mAbs) to begin reducing animal use in preclinical safety testing, before expanding to include other biological molecules and eventually new chemical entities. Findings from an accompanying pilot study on mAbs will be used to inform broader policy changes, and guidance updates will be rolled out in phases. The FDA and its federal partners will host a public workshop later this year to discuss the roadmap and gather stakeholder input on its implementation.

Industry response

Industry groups wasted no time in responding to the FDA’s recent announcement.

“This represents a natural progression of where research should go—so long as we have relevant and well-validated replacements for various animal models,” according to an American College of Laboratory Animal Medicine (ACLAM) statement to AVMA News, also noting it has long been common practice in the European Union and the U.K.

Still, a 2019 ACLAM position statement states, “humane research with animals is necessary to advance knowledge that is vital to preserving and improving health and quality of life for humans and animals.”

Meanwhile, the American Society of Laboratory Animal Practitioners (ASLAP) board of directors in a statement to AVMA News noted the growing adoption of NAMs and complementary methods across federal agencies, while emphasizing the importance of applying principles of the “3Rs” of animal research—replacement, reduction, and refinement—when animal models remain necessary to investigate safety and efficacy of therapeutics.

But across all methods, the ASLAP board emphasized the vital role federal veterinarians play in advancing science and public health, and the need to include them in ongoing and future discussions.

The National Association for Biomedical Research (NABR) emphasized an ongoing need for research involving animals, saying in an April 10 statement: “There is currently no full replacement for animal models in biomedical research and drug development.”

NABR further noted the FDA Modernization Act 2.0 allows the use of nonanimal testing methods when feasible, but does not remove the need for animal testing, adding, “Animal models are still essential for evaluating safety and efficacy.”