US Animal Welfare Act

The primary federal regulation concerning the care and use of laboratory animals in the United States is the Animal Welfare Act (AWA; Public Law 89–544 as amended, 7 USC Ch. 54). The AWA is implemented through the Animal Welfare Act Regulations, published in the Code of Federal Regulations (CFR), Title 9, Chapter 1, Subchapter A. The Act covers pets and warm-blooded animals used for research, testing, and exhibition purposes, but does not protect a number of animal species; for example, it specifically excludes rats of the genus Rattus, mice of the genus Mus, and birds bred for use in research.

The Animal Welfare Regulations consider painful procedures and methods to alleviate pain in several sections:

• §2.31(a), (d): Registered research institutions must have an institutional animal care and use committee (IACUC) that reviews and approves all procedures conducted using laboratory animals.
• §2.31(d)(i): “Procedures involving animals will avoid or minimize discomfort, distress or pain to animals.”
• §2.31(d)(ii): “The principal investigator has considered alternatives to procedures that may cause more than momentary or slight pain.”
• §2.31(e): “A proposal to conduct an activity involving animals … must contain … a description of procedures designed to assure that discomfort and pain to animals will be limited to that which is unavoidable for the conduct of scientifically valuable research including provision for the use of analgesic, anesthetic, and tranquilizing drugs where indicated and appropriate to minimize discomfort and pain to animals.”
• §2.33(a): “Each research facility shall have an attending veterinarian who shall provide adequate veterinary care to animals in compliance with this section.”
• §2.33(b)(4): The attending veterinarian shall provide “guidance to principal investigators and other personnel involved in the care and use of animals regarding handling, immobilization, anesthesia, tranquilization, and euthanasia.”

The United States Department of Agriculture (USDA) is responsible for the administration and enforcement of this act through its Animal and Plant Health Inspection Service (APHIS).

USDA Policies

The USDA through APHIS periodically issues and updates policies to clarify the provisions of the Animal Welfare Regulations and provide improved guidance to USDA personnel who inspect the regulated research programs. Two USDA policies address the requirement to recognize the potential for pain in association with research activities.

Health Research Extension Act

The Health Research Extension Act (Public Law 99–158, November 20, 1985, “Animals in Research”) provides the statutory mandate for the Public Health Service Policy on Humane Care and Use of Laboratory Animals (OLAW 2002 reprint of PHS Policy; preface). The Act mandates that “the Secretary [of the US Department of Health and Human Services], acting through the Director of NIH, shall establish guidelines for the following … [in procedures that may cause pain]: the proper treatment of animals while being used in research … shall require the appropriate use of tranquilizers, analgesics, anesthetics, paralytics, and euthanasia for animals.” The PHS Policy (see below) defines procedures to implement this mandate.

Public Health Service Policy on Humane Care and Use of Laboratory Animals

The Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy) (DHHS 2002) was introduced in 1973 and has been revised multiple times (most recently in 2002). The Policy applies to all institutions that use animals in research that is supported by any component of the PHS (e.g., NIH, CDC, FDA) and it “requires institutions to establish and maintain proper measures to ensure the appropriate care and use of all animals involved in research, training, and biological testing.” While the PHS Policy mandates compliance with the AWA and AWA Regulations, it uses a broader definition of an animal: “any live, vertebrate animal used or intended for use in research, training, experimentation, or biological testing.” Further, the Policy endorses the US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (see below) and requires institutions to base their animal care and use programs on the National Research Council’s Guide for the Care and Use of Laboratory Animals (NRC 1996).

The PHS Policy defines procedures for submission of the Animal Welfare Assurance statement, which is required of all institutions that conduct PHS-funded research, training, or testing with animals. For potentially painful procedures on animals, the PHS policy requires the IACUC to determine that “procedures with animals will avoid or minimize discomfort, distress, and pain to the animals, consistent with sound research design; procedures that may cause more than momentary or slight pain or distress to animals will be performed with appropriate sedation, analgesia, or anesthesia, unless the procedure is justified for scientific reasons in writing by the investigator; and animals that would otherwise experience severe or chronic pain or distress that cannot be relieved will be painlessly killed at the end of the procedure or, if appropriate, during the procedure.” The PHS Policy further states that “methods of euthanasia used will be consistent with the recommendations of the American Veterinary Medical Association” (AVMA 2007). Additionally, with respect to potentially painful procedures, the PHS Policy requires applications and proposals for PHS awards to include “a description of procedures designed to assure that discomfort and injury to animals will be limited to that which is unavoidable in the conduct of scientifically valuable research, and that analgesic, anesthetic, and tranquilizing drugs will be used where indicated and appropriate to minimize discomfort and pain to animals.”

The NIH Office of Laboratory Animal Welfare (OLAW) is responsible for administering the PHS Policy.

US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training

The US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (US Government Principles) were drafted in 1985 by the Interagency Research Animal Committee (IRAC 1985). The document addresses compliance with federal laws, policies, and guidelines and establishes overarching principles to consider when using animals in research, testing, and training. Principles 4, 5, and 6 relate to the potential to cause pain in laboratory animals.

• Principle #4: “Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals.”
• Principle #5: “Procedures with animals that may cause more than momentary or slight pain or distress should be performed under appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents.”
• Principle #6: “Animals that would otherwise suffer severe or chronic pain or distress that cannot be relieved should be painlessly killed at the end of the procedure, or if appropriate, during the procedure.”

Guide for the Care and Use of Laboratory Animals

The recommendations and guidelines of the Guide for the Care and Use of Laboratory Animals (7th ed.; NRC 1996; the Guide) were drafted by a committee of the National Research Council’s Institute for Laboratory Animal Research to promote the humane care and use of laboratory animals. The Guide emphasizes the application of performance standards and professional judgment and encourages users and institutions to achieve excellent standards of animal care and use by determining how best to achieve these goals within the scope and capabilities of the particular institution. The Guide also endorses the responsibilities of investigators as stated in the US Government Principles (IRAC 1985; outlined above). Both the PHS Policy and the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) require institutions to base their programs of animal care and use on the recommendations detailed in the Guide.

The Guide calls for the establishment of an IACUC, which must ensure the appropriate application of sedation, analgesia, and anesthesia when reviewing protocols (p. 9), and notes that “ethical, humane, and scientific considerations sometimes require the use of sedatives, analgesics, or anesthetics in animals” (p. 12). The Guide (p. 64) also devotes a section to the consideration of pain, analgesia, and anesthesia, and states that “an integral component of veterinary medical care is prevention or alleviation of pain associated with procedural and surgical protocols.” Although recognizing such pain is complex and can be challenging, the Guide indicates that the ability to experience and respond to pain is widespread in the animal kingdom. The Guide therefore stipulates that the proper use of anesthetics and analgesics in research animals is an ethical and scientific imperative and that in general, unless the contrary is known or established, it should be assumed that procedures that cause pain in humans also cause pain in animals.

Association for the Assessment and Accreditation of Laboratory Animal Care International

The Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) International is a private, nonprofit organization that promotes the humane care and use of laboratory animals through a program of voluntary assessment and accreditation. AAALAC International does not itself define standards but rather uses the Guide as its primary assessment resource along with other peer-reviewed reference standards. Additionally, when conducting assessments of accredited programs, AAALAC International requires that institutions comply with applicable principles, regulations, standards, policies, and guidelines concerning pain in laboratory animals.

American College of Laboratory Animal Medicine

The American College of Laboratory Animal Medicine (ACLAM) is the professional organization of veterinarians who have completed the requirements for board certification as specialists in laboratory animal medicine. ACLAM has issued position statements regarding Adequate Veterinary Care and Pain and Distress in Laboratory Animals.