Health authorities in the U.S. are continuing their move away from animal testing in drug development, with the FDA signaling an openness to new approaches that haven’t been validated and the National Institutes of Health (NIH) pledging a further $150 million to animal alternatives.
The FDA’s Center for Drug Evaluation and Research (CDER) released new draft guidance March 18 specifying that drug approval applicants are welcome to submit data from new approach methodologies (NAMs) like organoids, organs-on-chips and computational models, even if the method hasn’t previously been OK’d by the agency to replace animals.
The new guidance states that “NAMs for preclinical toxicology and safety testing can be validated, but clarifie[s] that neither validation nor qualification is necessary for them to be used to support a drug application,” a senior FDA official explained during a March 17 call with reporters.
“CDER is making it clear that we are hoping to receive appropriate NAMs data in place of animal data when available, as these data can be much more predictive and also a more ethical option,” the official added.
The administration requested that the officials on the call, two from the FDA and one from the NIH, not be named.
Validation and qualification are specific terms (PDF) related to the accuracy, reliability and relevance of a NAM for drug development and regulatory review.
The guidance, which is now open for public comment and could take a few months to finalize, provides a framework for drug developers to consider when submitting NAM data to the FDA. The core tenets are for the NAM to be used in a clearly defined context, be relevant to human biology, and be well characterized and fit for assisting the CDER in regulatory decision-making, according to the document.
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“This draft guidance advances our commitment to replace animal testing with human-relevant, scientifically rigorous methods,” Department of Health and Human Services Secretary Robert F. Kennedy Jr. said in a March 18 release. “Clear validation expectations will help modern tools earn regulatory confidence and speed safer, more effective therapies to patients.”
The FDA officials on the call were clear that animal testing won’t be replaced entirely, but that the new guidance represents what the agency considers to be a step in the right direction drug sponsors are also eager to make.
“We are taking a stepwise approach, and there is more flexibility when the drug belongs to a class of products where the molecular target is well characterized, etc.,” one senior FDA official said. “I’m coming from a review division [and] we have been helping the sponsors in terms of when to use them, how to use them.”
The fresh guidance builds on past efforts to phase out animal testing requirements for new monoclonal antibody drugs as well as a 2025 FDA road map (PDF) for reducing animal use in preclinical safety studies.
Asked by Fierce whether the FDA will provide any incentives—such as speedier reviews—for risk-averse companies to submit NAM data that haven’t been used by the regulator in the past, a senior agency official said there are currently no such plans.
“We’re hoping that the fact that the FDA has been really consistently announcing efforts to implement NAMs and reduce animal testing, since we released the roadmap in April of 2025, is going to make sponsors feel more secure about submitting their data,” the official said. Any sponsor unsure about using NAM data should reach out to their FDA review team, they added.
“We hope that it’s going to spread throughout the industry that we are really open to looking at the data in ways that we have not before,” the official said.
Over at the NIH, the first awards from the Complement Animal Research In Experimentation (Complement-ARIE) program have been announced, totaling $150 million. This comes on top of the NIH’s previously announced $87 million center for organoid development and a new office leading the charge on NAMs.
Through the new awards, the organization is “supporting technology development centers and a NAMs data hub and coordinating center,” the senior NIH official said on the call. The seven new technology centers, per a March 18 release, are “designed to stimulate the development of NAMs to address areas of greatest both scientific and regulatory need, with emphasis on biological complexity, throughput and data sharing.”
Some of the areas of need outlined in the release include gynecological disorders, cardiac disease, neurological disorders and rare diseases.
