For decades, manufacturers of pharmaceuticals, cosmetics, pesticides and other commercial chemicals have dutifully tested their products on rodents or other vertebrate animals to comply with government safety testing regulations. This long-standing practice is now starting to change.
The Environmental Protection Agency recently announced that it intends to phase out all mammalian animal testing requirements by 2035. The Food and Drug Administration has also been actively exploring non-animal alternatives to safety testing.
Reasons for Shift
The paradigm shift away from animal testing is being propelled by the convergence of ethical, economic, and scientific pressures. Animal rights proponents have long opposed animal testing, and this ethical campaign is strengthening with growing antipathy to animal tests by young consumers and scientists.
Economics provides a second rationale for considering alternatives to animal testing, as housing, feeding, and exposing animals under carefully controlled conditions is increasingly expensive. Because of the costs and facilities needed to conduct animal testing, only a small percentage of the chemicals in the marketplace have been adequately tested.
But perhaps the biggest surprise is the role that science is playing in pushing for non-animal alternatives. It has been known for years that animal tests do not always accurately predict human safety. For example, rats and mice give divergent results in safety testing for over 25% of substances. And the biological distance between humans and mice or rats is even wider. Reliance on animal tests therefore can produce false negative or false positive results that can have significant adverse consequences for human safety.
While this major flaw in animal tests has been known for years, there was no scientifically credible alternative. Until now.
A variety of new safety testing approaches, collectively called new approach methodologies (NAMs), have recently been developed. A NAM is any non-animal technology, methodology, or approach that can be used to provide information on chemical hazard and risk assessment. These include a variety of human cell in vitro systems, artificial organoids, “lab on a chip” technology, other high throughput screening methods, and computational or in silico tools in which machine intelligence conducts the analysis virtually.
The adoption of NAMs to replace animal tests got a big boost from the 2016 amendments to the Toxic Substances Control Act (TSCA), known as the Frank R. Lautenberg Chemical Safety for the 21st Century Act. The act requires the EPA to eliminate vertebrate animal testing to “the extent practicable” when regulating new and existing chemicals under the TSCA statute.
The act provides guidance to the EPA on when a NAM is ready to use, requiring them to be “scientifically reliable, relevant, and capable of providing information of equivalent or better scientific reliability and quality to that which would be obtained from vertebrate animal testing.”
While the recent scientific advances are promising, the replacement of animal tests with NAMs faces three hurdles for regulatory agencies such as the EPA and FDA.
First, agency scientists must validate the alternative methods and gain confidence in their capability to accurately predict human safety. This work is already well underway at the agencies, and given the advantages of the new methods, overcoming this first hurdle should be achievable as new techniques and tools are evaluated.
The second hurdle is the willingness of agency administrators to base regulatory decisions on these new methodologies. Human lives are at stake, and agency managers will understandably be cautious about relying on new and untried methods to make regulatory decisions. However, given the confluence of strong ethical, economic, and scientific pressures for NAMS, agency leaders will be incentivized to follow the advice of their scientists and show courage and innovation in advancing new methods.
The third hurdle is the most challenging, and that is to overcome the legal barriers to use of NAMs.
U.S. regulatory agencies operate in highly legalized environments, and are required to follow the procedure and substance specified by law. Both statutes enacted by Congress that give agencies their regulatory authority, and the regulations adopted by agencies to implement those statutes, are binding “law” under U.S. administrative law.
An agency that deviates from the procedural or substantive dictates of applicable statutes and regulations is likely to have its regulatory decisions overturned by reviewing courts.
Put to the Test
Here is where the rubber meets the road, because over the past decades of mandated animal testing, agencies such as the EPA and FDA have embedded animal testing requirements into their regulations, which have the force of law. Unless these existing regulations are resolved, regulators cannot mandate or even approve non-animal testing for product safety, and manufacturers will not have confidence that their non-animal testing will stand up to regulatory or judicial scrutiny.
This is another manifestation of the so-called “pacing problem” where outdated legal requirements impede new scientific developments.
Regulatory agencies may be able to use regulatory gymnastics to circumvent some of these existing legal barriers to reliance on non-animal testing. For example, the EPA recently enacted a waiver program to exempt some pesticides from mandated testing in birds. While such efforts may reduce some unnecessary animal testing, a more comprehensive solution is needed.
Agencies such as the FDA and EPA should act with anticipation now to start revising their own regulations to eliminate the mandatory use of animal tests in safety testing. Foresight today can prevent delay and inefficiency tomorrow.
This column does not necessarily reflect the opinion of The Bureau of National Affairs, Inc. or its owners.
Gary E. Marchant is Regents’ Professor and faculty director of the Center for Law, Science & Innovation at the Sandra Day O’Connor College of Law at Arizona State University. He researches and lectures on the legal response to emerging technologies.