FDA Seeks to Temper Animal Testing with Advisement from Science Board
By Brittany Wade
August 30, 2022 | In 1938, the US Food and Drug Administration (FDA) made animal testing a requirement for every new drug released under the Federal Food, Drug, and Cosmetic Act. Now, 85 years later, lawmakers and animal welfare groups are calling for the FDA to abolish animal testing for drugs, food, dietary supplements, cosmetics, medical devices, and tobacco.
For nearly a century, animal testing has played a critical role in drug development despite posing significant ethical and scientific concerns. Animal welfare groups point to animal suffering as the primary reason to prohibit the practice. Clinical researchers, who rely heavily on animal testing before conducting human clinical trials, cite unpredictable results and widespread inefficiencies as motivation to abandon animal-based models. Even the FDA admits that 92% of drugs passing pre-clinical animal testing fail in humans (Cambridge Quarterly of Healthcare Ethics, DOI: 10.1017/S0963180115000079).
Since animals differ significantly in morphology, biochemistry, metabolism, and neurophysiology, a drug that poses no risk to animals often proves toxic to humans. In contrast, many therapies that could be safe for human consumption are denied based on their demonstrated failures in animals.
With pressure from internal and external groups, the FDA convened with its Science Board, a distinguished committee of independent scientists, to seek advice on safely implementing non-animal approaches to drug regulation and development.
“While we are nowhere near being able to replace all animal testing, there are opportunities for alternative methods to make additional inroads,” said David Strauss, FDA Division of Applied Regulatory Science director and New Alternative Methods (NAMs) Working Group co-leader, to the Science Board in a June 14 meeting.
Strauss’ group, NAMs, “facilitates interactions with global regulatory bodies interested in implementing alternative methods in toxicology” to “replace, reduce, and refine animal testing.” The group argues that there is no shortage of suitable alternative approaches with advances in bioengineering, stem cell research, and mathematical modeling.
Setbacks and Loopholes
Regardless of the approach, each would need to pass the FDA’s extensive, rigorous, and multiphasic qualification program before being approved. Yet, the FDA rarely deems non-animal testing cases viable enough to demonstrate product safety.
One of the Science Board’s primary responsibilities will be to assist the agency in enhancing the qualification program, making it easier to approve other testing forms without losing the rigor that keeps Americans safe.
Many of these testing forms have “reached some degree of standardization and reliability,” said Janet Woodcock, FDA principal deputy commissioner and Cannabis Product Committee chair. She urged the Science Board to consider how these tools can be qualified for various uses.
According to an article written for Chemical & Engineering News, the uses are plentiful. For example, human pluripotent stem cells can detect developmental toxicity, and reconstructed epithelial cells mimic human corneas and skin. The latter, one of the few processes already approved by the FDA, replaced the use of rabbits for testing eye and skin irritation.
The National Toxicology Program proposed in vitro methods to replace mice in identifying botulinum neurotoxin, and the recent pandemic proved that next-generation sequencing could replace animals in detecting viral pathogens.
Even with various success stories surrounding non-animal testing, one of the main points of contention is the testing of cannabidiol (CBD), a pharmacologically active ingredient extracted from hemp. Before it was touted as a dietary supplement, CBD was tested as a drug, prohibiting its official label as a supplement and preventing product manufacturers from adding it to food.
Previous animal testing raised concerns regarding liver, immune, and reproductive toxicities. While the FDA can lift its CBD restrictions anytime, stakeholders insist that non-animal testing could clarify any ambiguity concerning its safety.
With the CBD market exploding, companies are eager to claim their stake in the industry. They could be incentivized to support alternative testing methods fully if the test results lead to CBD being permitted in all products.
One Step Forward, Two Steps Back
The FDA asked Congress for $5 million—to be delivered in fiscal 2023—to foster change and support NAMs’ mission. They also requested $7.5 million to help the National Center for Toxicological Research compare NAMs’ methods alongside traditional animal testing.
The additional funding request disappointed many stakeholders, as it would support continued animal suffering. “It would result in the death of many new animals for NAMs evaluation. So for NAMs intended for testing human products, this is a step back with regard to science and ethics,” said Elizabeth Baker, Physicians Committee for Responsible Medicine regulatory policy director, during public comments at a Science Board meeting.
To complicate matters further, Congress is also deciding whether to reauthorize the FDA’s ability to accept product developer user fees. These fees account for 40% of the agency’s budget and help speed up product review processes. While reauthorization could prevent mandatory animal testing, it will likely leave room for the FDA to allow it.