FDA seeks to reduce animal testing requirements for mAbs, other drugs

The US Food and Drug Administration (FDA) is loosening its requirement for animal testing of monoclonal antibodies (mAbs) and other drugs, the agency said in an announcement.

In its place, FDA will seek to reduce, refine, and replace the animal testing requirement where appropriate using real-world safety data from other countries with comparable regulatory standards as well as with New Approach Methodologies (NAMs) such as artificial intelligence (AI)-based toxicity and cell line computational models and organ-on-a-chip systems. The agency said the change will occur immediately for investigational new drug applications.

“For too long, drug manufacturers have performed additional animal testing of drugs that have data in broad human use internationally. This initiative marks a paradigm shift in drug evaluation and holds promise to accelerate cures and meaningful treatments for Americans while reducing animal use,” Martin Makary, FDA commissioner, said in a press release. “By leveraging AI-based computational modeling, human organ model-based lab testing, and real-world human data, we can get safer treatments to patients faster and more reliably, while also reducing R&D costs and drug prices. It is a win-win for public health and ethics.”

FDA provided several examples of the benefits of such a change. Using a software model to assess how a monoclonal antibody distributes through a human body and predict its side effects, for instance, would “drastically” reduce animal trials, an organ-on-a-chip system used to evaluate toxic effects of drugs in human organ systems might find safety issues that wouldn’t be identified through animal testing.

“For patients, it means a more efficient pipeline for novel treatments. It also means an added margin of safety, since human-based test systems may better predict real-world outcomes,” Makary said. “For animal welfare, it represents a major step toward ending the use of laboratory animals in drug testing. Thousands of animals, including dogs and primates, could eventually be spared each year as these new methods take root.

The agency said it would update its guidelines to reflect that it is now considering data from NAMs, and said companies that submit strong safety data from non-animal tests would receive a “streamlined review.” Focus reached out to US Department of Health and Human Services for clarification on what FDA considers a streamlined review, but did not receive a response before publication.

Reactions to announcement

Organizations weighed in on the news, including the People for the Ethical Treatment of Animals (PETA). PETA said the announcement was a “significant step towards meeting the agency's commitment to replace the use of animals.”

In a press release, the National Association for Biomedical Research (NABR) said there is “no full replacement” for animal models in drug development and biomedical research.

“We all want better and faster ways to bring lifesaving treatments to patients,” Matthew Bailey, NABR president, said in a press release. “But no AI model or simulation has yet demonstrated the ability to fully replicate all the unknowns about many full biological systems. That’s why humane animal research remains indispensable.”

Bailey also noted that AI is promising for research needs, but “largely depends on pulling from existing data,” noting that the “unknown variables could present the biggest risk to patients.”

FDA’s announcement is extremely positive and “well aligned with recent steps” taken by other regulatory entities such as the Environmental Protection Agency and European Medicines Agency as well as in the field of toxicology, Tyler Vandivort, associate director and regulatory lead at UCB Biopharma, told Focus in an interview.

“I think we have a lot of reason to be happy. This is where we should be going,” he said.

Vandivort, who is also a RAPS author and Convergence committee planning member, said the utility of animal models is a “constant source of debate,” with some people believing it is a cure-all without limitations, while others believe there is no value in animal testing.

“I think the truth lies somewhere in the middle,” he said.

Toxicologists who hesitant about discontinuing the use of animal models are likely willing to use another method if it is as good or better at predicting toxicity. “I think that's an entirely reasonable thing to demand because, ultimately, the next step for these products after pivotal toxicity testing is first-in-human studies,” Vandivort said.

It is also good business on top of good science, Vandivort explained, noting that animal testing for monoclonal antibodies requires the use of naïve non-human primates that can be cost prohibitive for start-ups as well as larger companies.

Vandivort noted he isn’t concerned about the potential for product safety being compromised when using artificial intelligence or organ-on-a-chip methods in place of animal testing. “I think that there's going to be an insistence that whatever we do, we can demonstrate that we’re just as good with the new method as with the existing intact animal models,” he said.

“With that being said, I don't think that toxicologists who receive this news with a healthy sense of scientific skepticism are wrong either,” he added.

As with all new models, there are challenges with pivoting away from animal testing. “I think people should feel really encouraged,” Vandivort said. “I don't think they should be worried that their drug products are going to be less safe. I think that they should be happy that given all of the recent turmoil at the FDA, that it's still thinking about something this important and putting resources into bringing it into utilization.”

Press release

FDA seeks to reduce animal testing requirements for mAbs, other drugs

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