Relevant Federal Laws and Agencies
Laws
The Food, Drug, and Cosmetics Act (FD&C Act) and the Animal Welfare Act (AWA) are federal laws that were promulgated to guide the practice of animal testing within the United States.
The FD&C Act was passed in the 1930s in an effort to enhance consumer protection against dangerous and ineffective drugs and deceptive product packaging. This law mandates the use of animal testing within the FDA’s approval process for new drugs by directing manufacturers to initially assess the toxicology and effectiveness of new products on animal subjects before advancing to human subjects; it does not allow for alternative testing methods.
The AWA establishes the regulation of and standards of care for the transportation, sale, and handling of certain animals, including within research facilities. The standards of care apply to the handling, housing, feeding, veterinary care, and pain minimization of research animals and requires lab personnel to be trained in humane animal handling. The animal care unit within the Animal and Plant Health Inspection Service (APHIS) of the U.S. Department of Agriculture (USDA) administers the AWA primarily by conducting pre-licensing inspections and unannounced compliance inspections of facilities engaged in the exhibition of animals, pet sales, animal-based research, and commercial transportation of animals. The stated purpose of these inspections is to ensure that animals within these facilities are receiving humane, adequate care.
Agencies
Other regulatory agencies and bodies work in conjunction with the FDA and USDA to oversee the practice of animal testing.
The U.S. Public Health Service (PHS) works to advance public health science and effectuate disease prevention programs across the country. In regard to animal testing, PHS administers the statutorily mandated Policy on Humane Care and Use of Laboratory Animals (Humane Care Policy), which works in tandem with the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training. Both set forth ethical considerations, welfare, and care requirements, while the PHS Humane Care Policy provides additional instruction for implementing these guidelines within institutions and by agencies tasked with oversight. The Office of Laboratory Animal Welfare (OLAW), within the PHS, is responsible for the administration of this policy. PHS is also responsible for overseeing two federal agencies closely involved in animal testing for biomedical research purposes, the FDA and the Centers for Disease Control and Prevention (CDC).
The FDA fulfills a duty of preserving public health by overseeing the efficacy and safety of drugs, biological products, medical devices, food, and cosmetic products through its regulatory authority and law enforcement. Within the FDA, the Center for Drug Evaluation and Research (CDER) is the entity that regulates all prescription and over-the-counter drugs and evaluates data from animal testing. As previously mentioned, the FDA was given its general oversight authority by the FD&C Act and mandates the use of animal testing in biomedical research.
The CDC increases health security by addressing and tracking global disease threats, promoting individual and community healthcare, and advancing health-related technology. While the CDC does not oversee animal testing in a regulatory sense, the CDC does perform a variety of animal tests and has been reprimanded for repeated violations of the AWA, and even temporarily lost its accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care in 2005.
The U.S. Department of Agriculture (USDA) is composed of 29 agencies and utilizes science and public policy to provide leadership on natural resources, food, nutrition, and rural development. One agency within the USDA, APHIS, houses the Animal Care Program, which works to ensure humane treatment for animals covered by the AWA, reviews welfare complaints against facilities engaged in animal related activities including animal testing, and performs inspections of such facilities.
In addition to these federal agencies, there are two types of other regulatory bodies involved in the oversight of animal testing: Institutional Animal Care and Use Committees and an accreditation organization, known as the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC). Each institution that engages in animal testing is required to form an animal care and use committee to review protocols involving animal tests and facility inspections and to ensure compliance with federal law. However, these committees are often subject to insufficient self-regulation. Any federal lab that is not subject to USDA inspection must be accredited by the AAALAC. Despite both the AAALAC and FDA’s suggestions that voluntary accreditation through the organization assures compliance with federal animal welfare standards, one study found that labs accredited by the AAALAC received more subsequent AWA citations than non-accredited labs, with demonstrated noncompliance in regard to AWA veterinary care standards and husbandry practices .
Problems Associated with Animal Testing
Animal testing has negative implications for both animals and humans. This practice lacks predictive value for subsequent clinical trials, can result in substantial harm to humans, lacks sufficient oversight and transparency by federal agencies, and is inhumane to animal test subjects, as will be discussed below.
Little Effect on Medical Progress
Animal testing is unnecessary for medical progress because it does not provide accurate models of human disease and lacks predictive value for outcomes of newly developed drugs in clinical trials. The discrepancies between animal and human health outcomes in biomedical research stem from disparities between models of disease between animals and humans and differences in genetics and physiology between animal species. Because researchers rely on artificially induced versions of human disease in animals, these studies fail to predict outcomes of new drugs in humans in 50 to 99.7 percent of cases. Further, while the use of animal testing is defended on the basis of being able to control factors that cannot be controlled with human test subjects, the added stress of the lab environment on animal test subjects often impacts research results and leads to uncontrollable changes such as increased cortisone and blood pressure and changes in neurochemistry and genetic expression. Without predictive value for the effect of new drugs in humans, animal testing serves very little purpose.
Potential for Human Harm
Harm to humans resulting from animal testing stems from misleading safety studies, abandonment of drugs that would be effective in humans but were ineffective in animals, and subjecting humans to dangerous drugs in clinical trials that appeared to be safe in animals. Moreover, disregarding effective drugs and testing dangerous drugs wastes the time and financial resources of those involved. The FDA has found that almost 90 percent of drugs tested in animals are not safe for human use; within the small percentage of drugs that do proceed to clinical trials, nine out of every 10 of those candidate drugs that appear safe and effective in animal studies fail when given to humans. In total, only about 12 percent of experimental drugs make it through clinical trials to the market. While almost all drugs that are deemed not safe for humans in animal testing do not proceed to clinical trials, factors like a delayed reaction to toxicity in the animal test subjects can allow a drug to deviate from the standard approval process. For example, tamoxifen (one of the most effective drugs for certain breast cancers) and cyclosporine (for organ transplant rejection) both showed toxicity in animals but were found to have substantial therapeutic value for humans.
Lack of Sufficient Federal Laws and Oversight
Both the FD&C Act and the AWA fail to fulfill their intended purposes. First, by exclusively requiring animal testing, the FD&C Act can put humans at risk by advancing dangerous drugs into clinical trials and rejecting effective drugs that fail in animal testing. Secondly, the AWA is limited in scope, excluding rats, mice, birds, fish, and reptiles from mandatory lab reporting requirements, which equate to roughly 95 percent of animals used in research. This allows for millions of animals each year to suffer in labs without sufficient oversight or care standards in place to protect them and drastically undermines figures published by the USDA related to animal testing.
In addition, the federal agencies involved with the oversight of animal testing within the United States struggle to fulfill their duties due to insufficient funding, staffing, and loopholes in the applicable federal laws. For example, the USDA’s Animal Care Program last reported that it employs 120 inspectors who are responsible for ensuring compliance across 12,000 facilities annually. Non-compliant facilities often only receive warning letters, with the USDA failing to pursue civil or criminal penalties, despite an overwhelming number of AWA violations across the country. A concern for this lack of oversight has been noted by animal welfare groups and members of Congress.
Inhumane Aspects of Animal Testing
Lastly, but of equal importance, is the inhumane nature of animal testing. An estimated 115 million animals are used in lab experiments annually worldwide, with up to 22 million used annually in the United States alone; approximately 85 percent of these are rats and mice. These millions of animals are subjected to conditions like forced chemical exposure, prolonged physical restraint, food and water deprivation, infliction of injuries and pain, induced diseases such as cancer, neck-breaking, and decapitation. It has been long established that animals are sentient, complex beings, and many believe that it is cruel to subject such large numbers to experimentation unless these experiments have been definitively proven to further human health and can be conducted in a humane manner.
Recommendations
Despite the complex problems associated with animal testing, there are multiple ways to address them. These include improving general legal protections for animals used in biomedical research by strengthening relevant laws, oversight, and penalty enforcement, further effectuating the principles set forth in the 3Rs alternative (which are discussed in more detail below), and considering existing alternative testing methods in place of animal testing.
Improving Legal Protections
Likely the most effective way to address the problems associated with animal testing is to amend the FD&C Act and AWA to provide stronger protections for animals used in research and to improve oversight and penalty enforcement of welfare standards in labs. H.R. 2565 and S.2952, known as the FDA Modernization Act, were introduced into the House of Representatives and Senate in 2021 and seek to remove the statutory mandate for animal testing within the FD&C Act to allow manufacturers and sponsors of a drug to use alternative testing methods to animal testing to investigate the safety and effectiveness of a drug. The FDA Modernization Act has the potential to drastically reduce the use of animal testing within biomedical research in favor of more accurate testing methods. Importantly, S.2952 was passed unanimously by the Senate in September of 2022. Similarly, the AWA could be improved by expanding the current definition of “animal” under the law and the USDA’s welfare and care requirements for animals in labs to incorporate all animals, including rats, mice, fish and birds. In regard to oversight and penalty enforcement, some potential actions that could be taken include increasing transparency into lab reports and experiment design, setting a mandatory reporting requirement for AWA violations, setting stricter guidelines for animal care and use committees within testing facilities, and increasing public awareness efforts of the reality of animal testing.
The 3Rs
Designing animal experiments consistent with the 3Rs could significantly reduce the pain and distress suffered by animal test subjects. The concept of the 3Rs—replacement, reduction, and refinement—was developed by scientists seeking to reduce the use of animals in lab experiments and is first explained in the book Principles of Humane Experimentation. Emphasis on the 3Rs in biomedical research is consistent with the FDA Modernization Act and places a higher moral and ethical obligation on researchers to their animal test subjects. While there is currently a lack of reliable metrics to monitor the use of the 3Rs within the context of toxicity testing, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) has been working since 2000 to increase the effectiveness of U.S. federal agency use of the 3Rs. ICCVAM, within the National Institute of Environmental Health Sciences (NIEHS), is a conglomerate of seventeen federal regulatory and research agencies that utilize and promote use of the 3Rs through developing new methods, modifying existing regulations, and providing trainings.
Alternative Testing Methods
There are multiple existing alternative testing methods that could decrease the inefficient use of animals in biomedical research and provide more accurate data regarding a new drug’s application to humans prior to clinical trials. Some of these methods include computer simulation, in vitro testing, human-patient simulators, and use of human volunteers. Computer simulation programs can be used to simulate human biological processes and developing diseases and address the pitfalls of poor experimental design and statistical analysis of an experiment’s results. In vitro testing refers to the use of biochemical or cell-based systems that mimic the structure and function of human organs and can be used to study the effects of new drugs and other consumer products. Human-patient simulators provide a better model for certain types of biomedical research because they can breathe, bleed, “die,” and mimic the muscle and tissue layers of human bodies. Lastly, human volunteers could be used in multiple contexts, such as to test small doses of new drugs through a method known as “micro-dosing” or through brain imaging and recording tests that can replace outdated experiments that are performed directly on the brains of living animals. All of these methods are consistent with the alternatives provided for in the FDA Modernization Act.
Conclusion
In the context of biomedical research, the use of animal testing is an unreliable, inefficient practice that results in animal and potential human harm while impeding progress in medicine. Though animal testing may never fully be phased out, it should be reevaluated in relation to the changing federal laws that provide for it, the variety of highly accurate alternative testing methods, and ethical principles that underly our society. This would help to protect animals, provide effective drugs to humans faster, and advance public health interests.