Twelve months after releasing a roadmap to shift away from animal testing requirements, the FDA has declared mission accomplished for its first-year goals. But experts have cautioned that there is still a long path ahead before animals are meaningfully removed from the drug development process.
“One year ago, we issued an ambitious roadmap to eliminate unnecessary animal testing and replace animal testing with more precise ways of predicting drug safety in humans,” FDA Commissioner Marty Makary, M.D., said in an April 19 release shared with Fierce Biotech. “In addition to ushering in more scientifically accurate way to test drugs before they are used in humans, the agency has made great strides to reduce research and development costs, which will lower drug prices for everyday Americans.”
This improved scientific accuracy, the FDA said in the release, could help rectify the fact that “more than 90% of drugs that clear animal studies do not receive FDA approval.”
In the release, the agency touted several initiatives put in place to promote the adoption of new approach methodologies (NAMs) as alternatives to animals. These include a searchable database for finding where NAMs can be used, a qualified AI tool for reading liver images, and draft guidance limiting primate testing of monoclonal antibodies and welcoming NAM data even if it hasn’t been previously okayed by the agency.
These efforts culminated in the agency hitting the one-year goals of its 2025 roadmap, the FDA said. The roadmap states that by 2030, and potentially as early as 2028, the FDA wants animal testing to become the exception in preclinical drug development rather than the norm.
Moving forward, the agency next wants to expand its NAM initiatives beyond antibodies, track changes in animal use, expand validation of NAMs that can address “critical drug development endpoints” and promote a cultural shift in drug development away from animals, the agency outlined in a year one report shared with Fierce, among other efforts.
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The National Association for Biomedical Research (NABR), a nonprofit organization that advocates for “ethical and essential animal research,” supports the FDA’s “goals to reduce reliance on animal models when scientifically feasible,” the association’s President Matthew Bailey told Fierce in an April 19 statement.
“However, we would like to provide context to FDA Commissioner Makary’s statement,” Bailey added.
When it comes to NAMs being more scientifically accurate, Bailey continued, “animal models and new approach methods are all surrogates of human disease.” Rather than one being superior to the other, “the context of use determines the choice of human surrogate method.”
As for Makary’s claim that 90% of drugs that pass muster in animals never secure approval, Bailey caveated that the numbers don’t get much better once human testing starts, either. Only 9.6% of drugs tested in humans ultimately get approved, he said, citing a report from the Biotechnology Innovation Organization that used data from 2006-15.
“When placed in the context of the overall drug development process, the animal study success rate is comparable to the human clinical trials success rate,” Bailey said. “We call on Commissioner Makary to also provide the success rate for drug development using NAMs only to inform this continuing discussion.”
“At the end of the day, regardless of which model is used, patient safety must remain the guide star of all drug approvals,” the NABR president said. “We’re a long way off from wholesale replacement of NAMs over full living systems.”
Steven Bulera, Ph.D., the chief scientific officer for safety assessment at contract research organization Charles River Laboratories, agreed that the animal testing shift is a marathon rather than a sprint.
“The transition to NAMs is evolutionary rather than revolutionary,” he told Fierce in an April 18 statement, highlighting CRL’s own efforts in the field.
That said, the CRO “applauds the FDA’s ongoing commitment to the field of alternatives, which is aligned with our own vision,” Bulera added.
It’s the most recent effort from the FDA, a draft guidance outlining that the regulator will consider data from NAMs like organoids and organ-on-chips even if they haven’t been validated by the agency, that could significantly push animal alternatives forward. But experts are split on how impactful the new guidance, released last month, will ultimately be.
“My first reaction was that this guidance is pretty refreshing and detailed compared to your typical FDA guidance,” Natalie Ma, Ph.D., chief business officer and co-founder of computational drug discovery outfit Deep Origin, told Fierce earlier this month. It provides “real examples” of relevant human biology and “concrete categories” of what the agency will consider, she said.
The guidance is lacking in discussion of computational models, she added, but because NAMs don’t have to be validated to submit data to the FDA, “computational predictions can start building a track record with reviewers now.”
Others were more critical. Vanda Pharmaceuticals issued a press release in March calling out the guidance’s lack of a clear example of an accepted NAM that fully replaces an animal test, scant scientific references, unclear authorship and “vague validation requirements.”
“While we applaud the FDA’s direction toward human-centric science, the draft guidance must strike a better balance between regulatory caution and the much-needed scientific reform that modern tools demand,” Vanda President and CEO Mihael Polymeropoulos, M.D., said in last month’s release
To that end, Vanda’s vision for the draft guidance is clear: withdraw it and replace it with one that has “stronger scientific grounding” and “clear, expedited pathways for regulatory acceptance.”
For NABR leader Bailey, one question looms above all others when it comes to ending animal testing.
“Would you volunteer for a human clinical trial knowing it had only been tested in a NAM?” he asked. “As of right now, I think most people would respectfully say no.”
