FDA pushes to replace animal testing

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The US Food and Drug Administration plans to introduce computational modeling and other innovative methods to replace animal testing in preclinical drug safety studies, according to a roadmap released in April. By encouraging drug sponsors to embrace organ-on-a chip, in silico modeling, organoid and other in vitro assays, the FDA aims to reduce animal testing to the extent that it becomes “the exception rather than the norm” within 3–5 years. The FDA’s roadmap builds on the 2022 FDA Modernization Act 2.0, passed by Congress, which removed the requirement for animal testing in biosimilar biologics’ applications.

Monoclonal antibodies are at the forefront of the FDA’s push for human-relevant safety testing as animal models are poor predictors of human safety for this drug class. In time, other biologics and small molecules will be included in the FDA’s plan. Nevertheless, technologies such as organs-on-chips and organoids, often called new alternative methods (NAMs), are not ready to fully replace animal testing just yet. Recapitulating organs is difficult, and NAMs must be validated to demonstrate they can mimic animal toxicity. Roche scientists showed that patient-derived intestinal organoids, for instance, can determine the on-target, off-tumor toxicities of T cell-engaging bispecific antibodies.

Developers are researching NAMs’ utility, but it is not known how much NAM data companies use in FDA submissions, as these documents are not made public. To increase NAMs’ knowledge base, the FDA is encouraging sponsors to submit NAM data in parallel with animal data. It is also identifying pilot cases in which an animal study might be waived, such as antibody drugs that target human-specific receptors. In such cases, the FDA could allow a sponsor to substitute organ-on-a-chip plus pharmacokinetic modeling studies instead of a transgenic mouse study.