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18 January 2023
New drugs for humans will no longer have to be tested on animals to receive approval from the US Food and Drug Administration (FDA). This does not mean that they will no longer use experimental animals, but rather that the entity may authorize a drug without this requirement.
Senate Bill S. 5002, “FDA Modernization Act 2.0,” relating to Animal Testing, passed by unanimous consent in September 2022. In December, Biden signed them into law as part of the Consolidated Appropriations Act, which funds the government through this fiscal year.
According to the 1938 stipulation, FDA typically requires toxicity tests on one rodent species such as a mouse or rat, and one non-rodent species such as a monkey or dog. Potential drugs not only must be tested for safety but also for efficacy in animals. In place, the new law allows FDA to promote a drug or biologic—a larger molecule such as an antibody—to human trials after either animal or non-animal tests.
With the regulation change, after more than 80 years, Congress appears to have responded to the emergence of new non-animal methods and growing public sentiment against animal research. Likewise, Namandjé Bumpus, FDA’s chief scientist, says the entity will support alternative methods that are backed by science and that demonstrate their safety and efficacy. "We continue to encourage developers who work on alternative methods to present their work," he specifies.
The new law defines non-clinical tests as: “a test conducted in vitro, in silico, or in chemico, or a non-human in vivo test that occurs before or during the clinical trial phase of the investigation of the safety and effectiveness of a drug, and may include animal tests, or non-animal or human biology-based test methods, such as cell-based assays, microphysiological systems, or bioprinted or computer models.”
Several in vitro approaches are positioned as animal alternatives. Organ chips are one of them. These chips typically consist of channels embedded in silicone-based polymers that are lined with living cells and tissue from organs such as the brain, liver, lungs, and kidneys. Thus, when liquids with experimental drugs run through them simulating the blood flow that circulates in living organs, the chip can give a toxicity alert if cells are damaged.
Organoids—hollow, 3D clusters of cells that are derived from stem cells and mimic specific tissues—offer another option to animals. They have shown promise in predicting liver and cardiac toxicities.
But pro-research groups, which advocate for animal research, argue that non-animal technologies can’t capture all the ways a drug might put human trial participants at risk. In addition, they are still “in their infancy” and won’t be able to replace animal models for years.
Zebrafish larvae assays for toxicity and efficacy assessment represent a powerful in vivo alternative since they are listed by the EU Directive 2010/63 as a non-animal model up to 5 days post-fertilization. As a whole organism assay, zebrafish offers mechanistic understanding in addition to behavioral and pathology endpoints. Thus, zebrafish-based assays can be used to reduce the uncertainties of in vitro assays while reducing mammal use.
Some drug companies considered the FDA's requirements for animal testing to be inefficient, arguing that animal studies cost them millions of dollars, slowing drug development and increasing the price of medications that did eventually reach the market. Hence, as considered by nonprofit animal welfare organizations, this regulatory change brings a WIN-WIN scenario, since both industry and patients in need of treatments can benefit from a faster drug R&D process.
Although it is not clear to what extent the new law will change things at the FDA, it admittedly opens the way for FDA and a company to seriously discuss whether alternatives are suitable.