Significant legislative changes have taken place since 2022 in the United States, with the passage of two laws modernizing the FDA (Food and Drug Administration), which is responsible in particular for bringing drugs to market.
The first law (the FDA Modernization Act 2.0), enacted in December 2022, updated the legal definition of non-clinical testing to include methods other than animal testing, such as in vitro testing or computer modeling (amending the 1938 law requiring potential drugs to be tested for safety and efficacy in animals). However, this is only a possibility, nothing is made compulsory, but the law introduces more flexibility and establishes a level of equivalence between animal testing and the new methods.
Under the second bill (which had a first version with a vote in December 2024 by the House of Representatives), passed in December 2025 by the U.S. Senate(S.355 – 119th Congress (2025-2026): FDA Modernization Act 3.0 | Congress.gov), the Secretary of Health and Human Services, acting through the Commissioner of Food and Drugs, shall issue, not later than one year after the date of enactment of the bill, an interim final rule to amend the Code of Federal Regulations to :
- replace any reference to “animal” tests, data, studies, models and research with a reference to non-clinical tests, data, studies, models and research, covering both traditional tests and new non-animal methods;
- add the definition of “non-clinical test” to the article in the Federal Law on Food, Medicines and Cosmetics.
This change aims to accelerate the drug development timetable, while promoting the use of human data in safety and efficacy assessments. This law requires the FDA to accelerate the process of updating its regulations and clarifying new testing standards.
” The FDA has taken important steps to finalize the transition away from mandatory animal testing, and FDAMA 3.0 provides the agency with the legal clarity needed to get the job done,” said Tamara Drake, director of research and regulatory policy at the Center for a Humane Economy. ” Updated regulations will eliminate confusion for drug developers, help reduce unnecessary testing on primates and beagles, and ensure that modern, human-specific tools continue to advance. It is essential that this progress is accompanied by a transparent and accountable regulatory process. “
With this opportunity comes the responsibility for manufacturers to provide convincing evidence of the predictivity, sensitivity and specificity of new methods to the highest scientific standards.
Already in April 2022, the FDA had authorized the launch of a human clinical trial based on efficacy data from experiments conducted on organs-on-a-chip. This trial, promoted by Sanofi, focuses on a rare disease, autoimmune demyelinating neuropathy (CIDP: Chronic inflammatory demyelienating polyneuropathy) : more information here
In parallel with these legislative developments, several announcements indicate that the US authorities wish to accelerate the transition to non-animal research.
April 10, 2025: FDA announces plan to phase out animal testing requirements for monoclonal antibodies and other drugs
The FDA’s animal testing requirement could be replaced by a range of other approaches, including computational models of toxicity based on artificial intelligence, cell lines and toxicity tests on organoids in the laboratory. Implementation of this program begins immediately for Investigational New Drug (IND) applications, where the inclusion of data from NAMs is encouraged, and is outlined in a roadmap also recently published.“This initiative marks a paradigm shift in drug evaluation and promises to accelerate meaningful treatments and cures for Americans while reducing animal use,” said FDA Commissioner Martin A. Makary.
April 10, 2025: FDA publishes roadmap to reduce animal testing in preclinical safety studies
This roadmap describes a strategic, step-by-step approach to enable the FDA to reduce animal testing in preclinical safety studies through scientifically validated New Methodological Approaches (NMAs), such as organ-on-a-chip systems, computational modeling and advanced in vitro testing. By partnering with federal agencies such as the NIH and the VA via ICCVAM, the FDA can accelerate the validation and adoption of these human-relevant methods, improving predictive accuracy while reducing animal use. This transition will improve public health by simplifying drug development and ensuring safer therapies reach patients faster, while positioning the FDA as a global leader in modern regulatory science and innovation.
To access this roadmap : click here
The NIH issued a statement along the same lines on April 29: click here
These announcements have been warmly welcomed by manufacturers of organs-on-a-chip and organoids: click here
On July 7, 2025, at an FDA and NIH workshop on reducing animal testing, an important new announcement was made: the end of funding for studies involving only animals: click here
January 22, 2026: The U.S. Environmental Protection Agency (EPA) announces that the goal of reducing animal testing has been reaffirmed, with a view to phasing it out by 2035.
EPA will prioritize the development and implementation of high-quality alternatives to reduce testing on vertebrate mammals, such as rabbits, mice, rats and dogs, while maintaining regulatory compliance and rigorous reference science to EPA’s “Make America Healthy Again” agenda. EPA will collaborate with other government agencies, researchers and other stakeholders to develop and validate the use of alternative methods for toxicity testing.
As a reminder, this target had been set in 2019, then called into question a few years later, before being set again in 2026.
For example, for the first time, the EPA’s Office of Pollution and Toxin Prevention (OPPT) has used alternative scientific methods to animal testing in its carcinogenicity assessments for dibutyl phthalate and di(2-ethylhexyl) phthalate, saving around 1,600 mice and rats from laboratory experiments.
In its announcement, the EPA points out that many animal tests are irrelevant to humans, and that new methodological approaches (NAMs) have the potential to be faster and cheaper, and more reproducible than animal tests. What’s more, for certain evaluation criteria, they can be used to test situations that cannot be tested in animals.
