The 1938 Mandate
The original Federal Food, Drug, and Cosmetic Act of 1938 was itself a response to tragedy. The sulfanilamide disaster of 1937 — in which an untested toxic solvent in a liquid antibiotic killed 107 people, many of them children — prompted Congress to require that drugs be tested for safety before marketing.
For 84 years, this requirement was interpreted to mandate animal testing. No new drug could reach human clinical trials without first being tested in at least 2 animal species: 1 rodent and 1 non-rodent. The beagle became the standard non-rodent. The 1938 law did not name the beagle — regulatory custom and ICH guidelines filled in the specifics.
Modernization Act 2.0 (December 2022)
Amended the Federal Food, Drug, and Cosmetic Act to state that drug sponsors may use “nonclinical tests or studies” — a term explicitly defined to include cell-based assays, organ chips, computer models, and other non-animal methods — instead of animal studies.
Sponsors are no longer legally required to conduct animal studies. They may choose to do so, and many will, but the statutory obligation is gone.
The law permits alternatives; it does not prohibit animal studies. Pharmaceutical companies remain free to test on beagles if they choose.
The FDA retains discretion to request animal data if it deems non-animal evidence insufficient. In practice, FDA reviewers accustomed to animal data continue to expect it.
Modernization Act 3.0 (December 2025)
Passed the United States Senate unanimously. Builds on 2.0 by:
Requiring formal guidance documents specifying how non-animal methods can satisfy regulatory requirements.
Setting deadlines for FDA to issue guidance and report on progress toward reducing animal testing.
Addressing not just new drugs but also biologics, biosimilars, and certain device applications.
The FDA Phase-Out Plan (April 2025)
mAbs are large-molecule biologics with well-understood mechanisms. For many mAbs, animal toxicology provides limited predictive value because the drugs are human-specific — they often don't bind to the target in animal species.
Sequential reduction across drug classes, prioritizing those where non-animal alternatives are most mature.
Sets directions, not deadlines. Individual drug applications evaluated case-by-case.