Replacing animal testing with alternate methodologies in preclinical drug trials holds potential for the development of cheaper, safer pharmaceuticals as well as alleviating animal suffering. But according to a new paper co-written by a University of Illinois Urbana-Champaign expert in legal issues surrounding cutting-edge medical developments, such a novel approach to drug trials needs to be implemented judiciously and with caution.
The U.S. Food and Drug Administration recently announced its commitment to replace animal testing in the development of monoclonal antibodies and other drugs with new approaches utilizing artificial intelligence-based computational models, "organ-on-a-chip" systems or so-called "organoids" that mimic human organs in order to test the safety profile of a drug.
Although it's a noble goal, phasing out animal testing too quickly without a validated replacement plan could ultimately backfire and raise safety and effectiveness concerns, says Sara Gerke, the Richard W. & Marie L. Corman Scholar at the College of Law.
"The primary goal of the FDA is to make animal testing the exception in 3-5 years, and a secondary goal is to get drugs to the market faster by reducing research and development costs," said Gerke, also a professor at the European Union Center at Illinois. "Those are all worthy and ambitious goals, but it's hard not to worry about the attendant risks in doing so. We really need to start thinking about how we ought to validate these new approach methodologies so that they're at least as effective as animal testing."
The paper, which will be published by the journal Trends in Biotechnology, was co-written by Jacob Balamut and Jennifer K. Wagner of Penn State University.
According to the paper, the FDA's roadmap to pivot from animal testing started in response to the rapid pace of technological progress as well as an effort to join a larger worldwide trend to reduce, refine or replace animal testing. Congress passed the FDA Modernization Act 2.0 in late 2022. In April 2025, the FDA announced its plan to immediately move away from animal testing in developing certain drugs, and that the utilization of newer, less-proven methods - dubbed the "New Approach Methodologies" or "NAMs"- would be encouraged.
The FDA also outlined a strategic, step-by-step approach for reducing animal testing in preclinical safety studies using scientifically validated NAMs even though most of the new methodologies "are currently not yet ready for prime time," Gerke said.
To incentivize the use of data from the new methods, the FDA also promised to update its guidelines to reflect the new approaches and to implement streamlined reviews for submitting strong safety data from nonanimal tests.
"This goal of making animal studies the exception rather than the rule for pre-clinical safety and toxicity testing within the next few years is likely overly optimistic given the current evidence as well as the absence of noninferiority or superiority studies with the new methodologies," Gerke said.
For example, among the new methodologies, AI is prone to biases, and computer modeling using AI "would need to be ethically designed with robust screening for those biases," Gerke said.
"Another reasonable approach could be implementing an FDA premarket review or an independent third-party certification process for NAMs," she said. "But at this point, there just needs to be more research that builds out the necessary evidence base for such an alternate approach."
Alternatively, since large-scale reform is time-consuming and difficult to achieve, drug companies could continue conducting animal testing in parallel to the new methodologies until sufficient data have been collected to demonstrate that they are at least as reliable as animal testing for predicting drug safety, the researchers said.
Overall, the FDA should insist on animal testing data to support the investigational use of new drugs until a specific NAM or NAM combination have been validated as substitutes for a specific context of use, Gerke said.
"There's certainly potential for new methodologies to become an important tool for reducing animal testing. With that said, rigorous validation is essential of these new methods, and we're just not there yet," she said.
The research was funded by the National Institutes of Health Office of the Director and the National Institute of Biomedical Imaging and Bioengineering. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
