The FDA announced Sept. 21 that it has issued a direct final rule to amend the language found in regulations pertaining to preclinical testing of pharmaceuticals and biotech products. As an example, the term “animal test” has been replaced by “nonclinical test,” as part of a focused effort to reduce the use of animals in drugs and biotech therapies with the use of new alternative methods (NAMs).
The Department of Health and Human Services (HHS) announced an umbrella program for NAMs in a Sept. 21 press release. HHS stated that it has launched more than 20 initiatives intended to foster the use of technologies in drug development that reduce the need for animal testing subjects. This includes development of human organoids and tissue models along with artificial intelligence and computational modeling algorithms in a series of grants issued by the National Institutes of Health (NIH).
NIH has awarded $88 million for development of related biomedical research infrastructure and has offered funding in the amount of $7 million for development of quantum computational approaches to NAM development. Other HHS agencies are also involved, including the Advanced Research Projects Agency for Health (ARPA-H) and the Centers for Disease Control and Prevention (CDC).
The FDA used the rarely invoked direct final rule to impose these changes on the regulations while simultaneously issuing a parallel rule in draft form that proposes the same changes. This use of the direct final rule, which is the subject of a November 1997 FDA guidance, allows the agency to immediately make the conforming changes, but also allows stakeholders to comment on the changes under the notice-and-comment rulemaking process.
The FDA said it will withdraw the direct final rule if the draft rule provokes significant adverse comment. In that scenario, the agency would then follow the notice-and-comment process to play out. Any comment received for the draft rule will be deemed to be applicable to the direct final rule.
Both the direct final rule and the draft rule replace terms such as “animal test” and “animal study” with “nonclinical test” and “nonclinical study.” The addition of these terms is not prohibitive of animal testing but allows manufacturers of pharmaceuticals and biotech products to make use of alternative methods for FDA premarket submission processes. The regulations pertaining to medical devices and in vitro diagnostics are not prescriptive as to the use of animal testing and hence there was no need to prepare a similar series of conforming amendments for FDA-regulated medical technologies.
Acting FDA commissioner Kyle Diamantas said the direct final rule allows developers to replace animal studies with studies that may better predict human response to these therapies. Diamantas added that the goal “is not to replace one rigid approach with another,” but rather to “support rigorous, modern science” that allows both animal and non-animal testing when those testing methods are properly validated.
The Food and Drug Omnibus Reform Act of 2022 stipulated that these changes be made to the regulation, and the FDA emphasized repeatedly that the changes are not intended to eliminate or prohibit animal studies. The agency provided a link to a database of NAMs, which have been used 25 times in connection with preclinical development of biotechnology products and pharmaceuticals.
The direct final rule is effective Feb. 4, 2027, and the FDA is accepting comment on the companion draft rule through Dec. 7, 2026. However, the agency will deem the direct final rule to be in effect within 30 days of the end of the comment period in the absence of any significant adverse comment.