The FDA has released a plan to stop or reduce the use of primates for testing the safety of certain monoclonal antibodies (mAbs), the latest expansion of the regulator’s efforts to eliminate animal testing in drug development.
In a draft guidance (PDF) published on Dec. 2, the agency outlined its recommendation that new antibodies designed to bind a single target—called monospecific antibodies—don’t need to be tested for six-month toxicity effects in non-human primates. Instead, drug sponsors can use three-month toxicity data from primates, dogs or mini-pigs and pair it with existing toxicity information from similar antibodies.
Even three-month studies are not always warranted, the FDA added, including in cases where shorter-term toxicology studies have resulted in animals developing antibodies against the new drug or side effects such as anemia that indicate they likely wouldn’t survive a longer dosing regimen.
If data from other antibodies that bind the same target has proven unable to predict human toxicity, the agency added, there’s no need for new drug sponsors to test their asset in three-month animal studies too.
The new guidance does not cover products reviewed by the Office of Oncologic Diseases. Antibody-drug conjugates, multi-specific antibodies and antibody constructs such as single-chain variable fragments are also not included.
“We applaud the FDA’s commitment to the ‘3Rs’ (Replacement, Reduction and Refinement) in the new guidance document,” Matthew Bailey, president of the National Association for Biomedical Research, told Fierce. However, there is not enough data from existing antibodies for HIV/AIDS and rare cancers and autoimmune diseases to pair with three-month toxicology data, he said.
“Research with nonhuman primates and other animals remains crucial beyond the three-month toxicity studies for these mAbs,” Bailey added.
Preclinical monoclonal antibody programs can use as many as 100 primates—mostly macaques—for safety testing, the FDA said in the release, at a cost of about $50,000 per animal.
“We are delivering on our roadmap commitment to eliminate animal testing requirements in drug evaluation and our promise to accelerate cures and meaningful treatments for Americans,” FDA Commissioner Marty Makary, M.D., said in a Dec. 2 release.
“Modern science has given us far more effective and humane ways of evaluating drug safety than animal testing,” Makary added. “This reform may reduce the amount of time it takes to bring a drug to market and lower research and development costs, which can translate into lower drug prices.”
The FDA encourages sponsors to discuss plans to use animal testing alternatives, called new approach methodologies or NAMs, in their official meetings with the regulator, including in Type B meetings, where sponsors share plans to advance an investigational program into the next phase of development.
The draft guidance follows recent reports that the Centers for Disease Control and Prevention has ordered staff to halt all monkey research by the end of the year.
The FDA first announced plans to phase out animal testing requirements for new monoclonal antibody drugs in April. At the time, the National Association for Biomedical Research, a nonprofit organization that advocates for “ethical and essential animal research,” cautioned that NAMs are not yet ready to take over for animals.
The NIH has followed the FDA’s lead, opening a new office to lead the agency’s charge on NAM development and earmarking $87 million for a new organoid center. In August, the Foundation for the National Institutes of Health, a congressionally mandated nonprofit that supports the NIH's mission, launched a public-private partnership network meant to support promising NAMs.
Charles River Laboratories, one of the world's largest contract research organizations, praised the FDA's new guidance. The CRO has been making its own shift away from animal testing, recently appointing former FDA Principal Deputy Commissioner Namandjé Bumpus, Ph.D., to helm a NAM scientific advisory board.
"Charles River applauds the FDA’s commitment to enhancing animal welfare in the development of monoclonal antibodies," a company spokesperson told Fierce. "This is an area where a wealth of data exists, and the FDA has now provided regulatory guidance to allow the industry to further embrace the 3Rs."
Editor's note: This story was updated at 2:35 p.m. ET with a statement from the National Association for Biomedical Research.