Regulatory Compliance

Table of Contents

• I. Introduction
• II. The Guide for the Care and Use of Laboratory Animals

• Chapter 1. Intsitutional Policies and Responsibilities
• Chapter 2. Animal, Environnment, Housing, and Management
• Chapter 3. Veterinary Medical Care
• Chapter 4. Physical Plant

• III. The Animal Welfare Act

• Part 1. Definition of Terms
• Part 2. Animal Welfare Regulations (AWR)
• Part 3. The Animal Welfare Regulations Standards

• IV. The Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals
• V. Good Laboratory Practice Regulations (GLP's)
• VI. Association for Assessment and Accreditation of Laboratory Animal Care International, Inc. (AAALAC) Accreditation Program
• VII. Acknowledgements

I. Introduction

Use of animals in biomedical research is regulated by multiple organizations that share common goals of ensuring humane care and use and advancement of science. While the regulatory "burden" and paper work can be intimidating and time consuming, these regulations have contributed to many significant, positive advances and refinements in animal research over the last several decades.

Oversight of regulatory compliance at institutions using animals in research is assigned to the Institutional Animal Care and Use Committee (IACUC). The primary functions of an IACUC are to review and inspect all aspects of an institution's animal care and use program including all animal facilities and animal care records, review animal use protocols, review and investigate complaints about animal use, and make recommendations to the Institutional Official. Details about committee composition, roles and responsibilities are highlighted throughout this chapter under respective regulatory guidelines.

On-line guidance for IACUC committees is available through Animal Welfare Information Center (AWIC) (www.nal.usda.gov/awic/). This site is maintained by the USDA and provides information for improved animal care and use in research, teaching, and testing. Additionally, IACUC.ORG (www.iacuc.org/) is a link archive produced by the American Association for Laboratory Animal Science (AALAS) and contains information resource for members and staff of institutional animal care and use committees.

The goal of this chapter is to introduce the main governing agencies and current guidelines, summarize key elements from each, and provide additional resources to learn more information. Although each guideline shares similar objectives, they often differ in terms of institutional/organizational coverage as well as the definition of covered laboratory animals.

II. Guide for the Care and Use of Laboratory Animals

This document is written by the Committee to Revise the Guide, Institute for Laboratory Animal Resources, National Research Council, and National Academy of Sciences and was published by the National Academy Press, Washington, D.C., 1996. The Guide was first published in 1963; this is the sixth revision.

The purpose of the Guide is to assist institutions in caring for and using animals in ways judged to be scientifically, technically, and humanely appropriate.

Laboratory Animal Definition: Any vertebrate animal used in research, teaching or testing.

The Guide applies to farm animals used in biomedical research, including those maintained in typical farm settings. Another useful resource is the Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching (1988).

Performance standards are preferred over Engineering standards. Performance standards define an outcome in detail and provide criteria for assessing that outcome, but do not limit the methods by which to achieve outcome goals. Scientific information should be used in evaluating performance and engineering standards.

The verb "must" is used for basic aspects that the Guide considers imperative.

The verb "should" is used as a strong recommendation for achieving a goal. However, the Committee recognizes that individual circumstances might justify an alternative strategy.

The Guide endorses:

1. USA Government Principles for Utilization and Care of Vertebrate Animals Used in Testing, Research and Training.
2. Federal Animal Welfare Regulations
3. P.H.S. Policy on Humane Care and Use of Laboratory Animals
4. Other applicable federal, state, and local laws, regulations and policies

An Abbreviated Summary of the Major Points for the Guide for the Care and Use of Laboratory Animals

Chapter 1. Institutional Policies and Responsibilities

Monitoring the Care and Use of Animals

Institutional Animal Care and Use Committee (IACUC) -  The IACUC is appointed by the responsible administrative official at each institution (CEO) to oversee the animal use program, procedures and facilities, and to ensure that they are consistent with the recommendations in the Guide, the Animal Welfare Regulations (AWR), and the Public Health Service (PHS) Policy.

Committee membership should include a veterinarian with training or experience in laboratory animal medicine, a scientist with experience in laboratory animal research, and a public member not affiliated with the institution.

The IACUC must meet at least once every 6 months and should inspect the animal facilities at least as often.

Functions of the committee include inspection of facilities; evaluation of programs and animal activity areas; reports to responsible institutional official; review of proposed uses of animals in research, testing or education; and establishment of a mechanism for handling animal use concerns.

Animal Care and Use Protocols should be reviewed in accord with the AWR; PHS Policy; the USA Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training; and the Guide.

Physical Restraint is defined as the use of manual or mechanical means to limit some or all of an animal’s normal movement for the purpose of examination, collection of samples, drug administration, therapy, or experimental manipulation.

Prolonged restraint, including chairing of nonhuman primates, should be avoided unless it is essential for achieving research objectives and is approved by the IACUC.

The following are important guidelines for restraint:

• Restraint devices are not to be considered normal methods of housing.
• Restraint devices should not be used simply as a convenience in handling or managing animals.
• The period of restraint should be the minimum required to accomplish the research objectives.
• Animals to be placed in restraint devices should be given training to adapt to the equipment and personnel.
• Provision should be made for observation of the animal at appropriate intervals.
• Veterinary care should be provided if lesions or illnesses associated with restraint are observed.

Multiple Major Surgical Procedures - Major surgery is defined as a procedure that penetrates and exposes a body cavity or produces substantial impairment of physical or physiologic function.

Multiple major survival surgeries are discouraged but may be permitted with scientific justification and IACUC approval.

Multiple major survival surgeries can be justified if they are related components of a research project, if they will conserve scarce animal resources, or if they are needed for clinical reasons. Cost savings alone is not an adequate reason.

Food or Fluid Restriction for research purposes should be scientifically justified, and a program should be established to monitor physiologic and behavioral indexes, including criteria (such as weight loss or state of hydration) for temporary or permanent removal from the protocol.

Precautions that should be used in cases of fluid restriction to avoid acute or chronic dehydration include daily recording of fluid intake and recording of body weight at least once weekly (or more often for small animals such as rodents).

The least restriction that will achieve the scientific objective should be used, and in the case of conditioned-response protocols, use of highly preferred food or fluid as positive reinforcement is recommended instead of restriction.

Veterinary Care

Veterinarians must provide care, including access to all animals for evaluation of their health and well-being. For specific responsibilities of the veterinarian, see Veterinary Medical Care.

Vet must provide investigators with advice on use of sedatives, analgesics, or anesthetics in animals. The AWR and PHS Policy require that the attending veterinarian have the authority to oversee the adequacy of other aspects of animal care and use.

Personnel Qualifications and Training

AWR and PHS Policy require institutions to ensure that people caring for and using animals are qualified. Personnel caring for animals should be appropriately trained and the institution should provide for formal or on-the-job training to facilitate effective implementation of the program and humane care and use of animals.

Occupational Health and Safety of Personnel

An occupational health and safety program must be part of the overall animal care and use program.

Hazard Identification and Risk Assessment - Professional staff who support research programs that involve hazardous biologic, chemical, or physical agents should be qualified to assess dangers associated with the programs and to select safeguards appropriate to the risks.

Personal Hygiene - Clothing suitable for use in the animal facility and laboratories in which animals are used should be supplied and laundered by the institution. Outer garments worn in the animal rooms should not be worn outside the animal facility. Personnel should not be permitted to eat, drink, use tobacco products, or apply cosmetics in animal rooms.

Facilities, Procedures, and Monitoring - Experimental animals should be housed so that potentially contaminated food and bedding, feces, and urine can be handled in a controlled manner.

Animal Experimentation Involving Hazards - Institutions should have written policies governing the use of hazardous biologic, chemical, and physical agents. Relevant publications include Biosafety in Microbiological and Biomedical Laboratories (CDC and NIH, 1999) and Occupational Health and Safety in the Care and Use of Research Animals (NRC).

Medical Evaluation and Preventive Medicine for Personnel - A program of medical evaluation and preventative medicine should be developed and implemented.

Animal care personnel should be immunized against tetanus, and pre-exposure immunization should be offered to people at risk of infection or exposure to rabies and hepatitis B virus.

Zoonosis surveillance should be part of an occupational-health program:

• Personnel who have contact with nonhuman primates (NHP) or have duties in NHP housing areas should be routinely screened for Mycobacterium tuberculosis (TB).
• All personnel who work with macaques should have access to and be instructed in the use of bite and scratch emergency-care stations, and a procedure should be established for ensuring medical care for bites and scratches.

Chapter 2. Animal, Environment, Housing, and Management

Physical Environment

Proper housing and management of animal facilities are essential to animal well-being, to the quality of research data and teaching or testing programs in which animals are used, and to the health and safety of personnel.

Micro- and Macroenvironment - The microenvironment of an animal is the physical environment immediately surrounding it (the primary enclosure). The animal’s macroenvironment is the physical environment of the secondary enclosure (such as a room).

Housing -  Should allow for normal, physiologic and behavioral needs of the animals, and conspecific social interaction. Animals must be able to remain clean and dry with adequate ventilation, and have easy access to food and water. Rodents prefer solid-bottom floors with bedding.

Rodents are often housed on wire flooring, which enhances sanitation of the cage by enabling urine and feces to pass through to a collection tray. However, some evidence suggests that solid bottom caging, with bedding, is preferred by rodents. Solid-bottom caging, with bedding, is therefore recommended for rodents.

Space Recommendations - An animal's space needs are complex, and consideration of only the animal's body weight or surface area is insufficient.

Whenever it is appropriate, social animals should be housed in pairs or groups, rather than individually, provided that such housing is not contraindicated by the protocol in question and does not pose an undue risk to the animals. Mice are thigmotactic (prefer more wall space than floor space).

Recommended space requirements are listed in Tables 2.1-2.3 of the Guide (pp. 27-31).

Temperature and Humidity - Animals can adapt to temperature extremes by physical, behavioral, or morphologic mechanisms.

Regulation of body temperature within normal variation is necessary for the well-being of homeotherms. Generally, exposure of unadapted animals to temperatures above 85ºF (29.4ºC) or below 40ºF (4.4ºC), without access to shelter or other protective mechanisms, might produce clinical effects that could be life-threatening.

In the absence of well-controlled studies, professional judgment and experience have resulted in recommendations for dry-bulb temperatures for several common species (Table 2.4 of the Guide p. 32).

Relative humidity should be controlled to the acceptable range of 30% to 70%.

Ventilation - The purpose of ventilation is to supply adequate oxygen; remove thermal loads caused by animal respiration, lights and equipment; dilute gaseous and particulate contaminants; adjust the moisture content of room air; and, where appropriate, create static-pressure differentials between adjoining spaces.

An acceptable guideline is 10 - 15 fresh air changes per hour; however, this guideline does not allow for species size, number of animals, or heat load of enclosure.

Illumination - Light can affect the physiology, morphology, and behavior of various animals. Potential photostressors include inappropriate photoperiod, photointensity, and spectral quality of the light.

In general, lighting should be diffused throughout an animal holding area and provide sufficient illumination for the well-being of the animals and to allow good housekeeping practices, adequate inspection of animals-including the bottom-most cages in racks-and safe working conditions for personnel.

Light levels of about 325 lux (30 ft-candles) about 1.0 m (3.3 ft) above the floor appear to be sufficient for animal care and do not cause clinical signs of phototoxic retinopathy in albino rats, and levels up to 400 lux (37 ft-candles) as measured in an empty room 1 m from the floor have been found to be satisfactory for rodents if management practices are used to prevent retinal damage in albinos.

Noise should be as minimal as possible as it may have different effects on different animals.

Noisy species such as dogs, swine, and nonhuman primates should be housed away from quiet species such as rodents, rabbits, and cats. Exposure to sound louder then 85 dB can have auditory and nonauditory effects.

Behavioral Management

Structural Environment - The structural environment consists of components of the primary enclosure such as cage furniture, equipment, and objects for enrichment, and should be modified to accommodate the needs of animals.

Social Environment - Consideration must be given to an animal’s need for social interaction with other members of its species (conspecifics) with an understanding of their normal social behavior. Factors such as population density, space, familiarity among animals and social rank should be considered when animals are grouped together.

Activity includes motor cognitive activity and social interaction. Animals should have the opportunity to exhibit species-typical activity. Activity should not be forced or restrict other behaviors, and should be goal-oriented.

Husbandry

Food - Animals should be fed palatable, uncontaminated, and nutritionally adequate food according to their particular requirements. Most dry diets can be used for 6 months after the manufacturing date. Temperatures higher than 21ºC hasten food deterioration. Autoclavable diets require adjustments in the type of ingredients used.

Vitamin C in manufactured feeds, however, has a shelf-life of only 3 months. The use of stabilized forms of vitamin C can extend the shelf-life of feed.

Water - Animals should have easy access to clean, uncontaminated drinking water. Automatic watering devices should be checked daily to ensure they are functioning properly. Monitoring of pH, hardness, and microbial or chemical contaminants should be done periodically.

Bedding - Appropriate bedding material should accommodate the needs of the specific species and should be sufficient to keep the animals dry between cage changes. Frequent changes should not occur during pre- and postpartum periods.

The use of cedar shavings for bedding is discouraged because they emit aromatic hydrocarbons that affect liver enzymes.

Sanitation - Maintenance of sanitary conditions should be conducive to health, and depend on what is needed to ensure a healthy environment for the animal. Wash and rinse water should be between 143 - 180ºF for effective disinfection.

Solid bottom rodent cages should be sanitized at least once a week, while cage accessories should be sanitized at least once every two weeks.

Rabbits produce urine with large amounts of protein and minerals; therefore, an acid rinse is often required before the cage is washed.

Pest control should include prevention of vermin entry and harborage. Use of substances such as silica gel or boric acid are acceptable, but not regular use of pesticides.

Weekend, Holiday, and Emergency Care - Animals should be cared for by qualified personnel every day, including weekends and holidays, both to safeguard their well-being and to satisfy research requirements. Emergency veterinary care should be available after work hours, on weekends, and on holidays. In the event of an emergency, institutional security personnel and fire or police officials should be able to reach people responsible for the animals.

A disaster plan that takes into account both personnel and animals should be prepared as part of the overall safety plan for the animal facility.

Population Management

Identification and Records - Good record-keeping in animal areas is critical and should include source of the animal, strain, name and room number of the investigator, and protocol numbers. Any type of experimental manipulations should be clearly documented.

Toe-clipping, as a method of identification of small rodents, should be used only when no other individual identification method is feasible and should be performed only on altricial neonates. Identification cards should include the source of the animal, the strain or stock, names and locations of the responsible investigators, pertinent dates, and protocol number, when applicable.

Genetics and Nomenclature - Record-keeping with standardized nomenclature of the genetic background of animals in studies is important. Several publications provide guidelines to standardized nomenclature of outbred (low level of homozygosity), inbred (high level of homozygosity), and transgenic animals.

Chapter 3. Veterinary Medical Care

Veterinary medical care is an essential part of an animal care and use program. Adequate veterinary care consists of programs for:

• Preventative medicine
• Surveillance, diagnosis, treatment and control of disease, including zoonosis control
• Management of protocol-associated disease, disability, or other sequelae
• Anesthesia and analgesia
• Surgery and post-surgical care
• Assessment of animal well-being
• Euthanasia

A trained attending veterinarian must provide guidance to investigators to ensure appropriate handling, immobilization, sedation, analgesia, anesthesia, and euthanasia. Additionally, he or she must provide guidance for surgery programs and oversight of post-surgical care.

Animal Procurement and Transportation

All animals must be obtained lawfully. If dogs or cats are obtained from a Class B dealer or pounds, they must be inspected for identification (transponder chips, tattoos). If found, ownership must be verified. Class A dealers (purpose-bred animals) provide genetic and pathogen status of the animals.

Transportation of animals should be conducted to:

• Minimize transit time and the risk of zoonosis
• Protect against temperature extremes
• Avoid overcrowding
• Provide food and water
• Protect against physical trauma

Documents providing details and guidelines for animal procurement and transportation include:

• Animal Welfare Regulations (AWR)
• International Air Transport Association’s Live Animal Regulations (IATA)
• Public Health Service (PHS)
• Centers for Disease Control (CDC) (specifically for nonhuman primates)

Preventive Medicine

An effective quarantine minimizes the chance for introduction of pathogens into an established colony. The veterinary medical staff should have procedures for evaluating the health and, if appropriate, the pathogen status of newly received animals, and the procedures should reflect acceptable veterinary medical practice and federal and state regulations applicable to zoonoses.

Newly received animals should be given a period for physiologic, psychologic, and nutritional stabilization before their use.

Quarantine, Stabilization, and Separation - The veterinary medical staff should have procedures in place for evaluating the health and, if appropriate, the pathogen status of newly received animals.

All newly received animals should be given a period of acclimatization (the physiologic, psychologic and nutritional stabilization of newly received animals) before use. The required length of time depends on the species, period of travel, and intended use.

Animals should be separated by species to prevent interspecies disease transmission and to eliminate potential interspecies conflict.

Surveillance, Diagnosis, Treatment, and Control of Disease - A person trained to recognize such signs should observe all animals for signs of illness, injury, or abnormal behavior. As a rule, this should occur daily, but more-frequent observations might be warranted.

It is imperative that appropriate methods be in place for disease surveillance and diagnosis. Unexpected deaths and signs of illness, distress, or other deviations from normal in animals should be reported promptly to ensure appropriate and timely delivery of veterinary medical care.

Methods of disease prevention, diagnosis, and therapy should be those currently accepted in veterinary practice. The choice of medication or therapy should be made by the veterinarian in consultation with the investigator.

Scientific objectives of a particular protocol, the consequences of infection within a specific strain of rodent, and the adverse effects that infectious agents might have on other protocols in a facility should determine the characteristics of rodent health-surveillance programs and strategies for keeping rodents free of specific pathogens.

Surgery

The IACUC is responsible for determining if personnel are appropriately trained to perform surgical procedures. Pre-surgical planning should incorporate post-surgical monitoring, care, record-keeping, and identification of responsible personnel. The veterinarian and the principal investigator share responsibility for ensuring that post-surgical care is appropriate.

Intra-operative monitoring of factors such as anesthetic depth, physiologic function, and body temperature are also important for successful surgery.

Since most bacteria are carried on airborne particles or fomites, surgical facilities should be maintained and operated in a manner that ensures cleanliness and minimizes traffic.

Autoclaving and gas sterilization are common methods used for sterilizing materials. Sterilization indicators should be used to verify effective treatment.

Alcohol is neither a sterilant nor a high-level disinfectant. The use of antibiotics should never be considered as a replacement for aseptic procedures.

Major Survival Surgery - is defined as procedures that penetrate or expose a body cavity or produce substantial impairment of physical or physiologic function (laparotomy, craniotomy, limb amputation, joint replacement).

Minor Surgery - does not expose a body cavity and causes little or no physical impairment.

Examples include:

• Wound suturing
• Peripheral-vessel cannulation
• Routine farm procedures (castration, dehorning, repair of prolapses)
• Most procedures routinely done on an outpatient basis in veterinary clinical practice.

Minor surgeries still require aseptic technique and instruments, and appropriate anesthesia.

In Non-Survival Surgery, animals are euthanized before recovery from anesthesia. It may not be necessary to follow all of the guidelines outlined for survival surgery, but at a minimum, the surgical site should be clipped, the surgeon should wear gloves, and the instruments and surrounding area should be clean.

Pain, Analgesia, and Anesthesia

Prevention or alleviation of pain is an integral part of veterinary medical care. Species vary in their response to pain. Unless otherwise known, it should be assumed that procedures that cause pain in humans also cause pain in animals. Neuromuscular blocking agents do not provide relief from pain, and they are not a substitute for adequate pain relief by other analgesics.

Euthanasia

Euthanasia is the act of killing animals by inducing rapid unconsciousness and death without pain or distress. Important factors include:

• Reliability
• No reversibility
• Time to loss of consciousness
• Species and age limitations
• Compatibility with research objectives
• Safety to and emotional effect on personnel

The selected technique must be consistent with the most recent revision of the Report of the AVMA Panel on Euthanasia and approved by the IACUC. Personnel must be properly trained, and death must be confirmed.

Chapter 4. Physical Plant

The key to a successful animal care program starts with the physical requirements of an institution. Specific facilities are needed for good animal management and human comfort.

Computational Fluid Dynamic (CFD) modeling might be useful. CFD uses computer simulation and analysis of airflow patterns while allowing alteration of the size, type, number, and location of air supply and exhaust systems.

Functional Areas

Professional judgment should be exercised in the development of a practical, functional, and efficient physical plant for animal care and use. The size, nature, and intensity of an institutional animal program will determine the specific facility and support functions needed.

Most multipurpose animal facilities also include the following:

• Specialized laboratories near animal-housing areas for such activities as surgery, intensive care, necropsy, radiography, preparation of special diets, experimental procedures, clinical treatment, and diagnostic laboratory procedures.
• Receiving and storage areas for food, bedding, biologics, and supplies.
• Space for washing and sterilizing equipment and supplies; a utility sink; an autoclave; and separate areas for holding soiled and clean equipment.
• Space for cold storage or disposal of carcasses.
• Space for administrative and supervisory personnel.
• Security features, such as card-key systems, electronic surveillance, and alarms.

Construction Guidelines

Corridors should be 6 - 8 ft wide. Items on the walls such as water lines, drain pipes, etc. should be recessed.

Animal Room Doors should be approximately 42 in. wide by 84 in. high and should open into the rooms.

Exterior windows are acceptable for environmental enrichment in some species, but inappropriate if photoperiod is important (e.g., rodent breeding colonies).

Floors should be moisture-resistant, nonabsorbent, impact-resistant, and resistant to urine and biological materials. Monolithic flooring, or flooring with minimal joints, is preferred; the floor should also be relatively smooth, depending on the species housed in the room.

Drainage is not necessary in all rooms (such as rodent rooms). Where floor drains are used, the floors should be sloped and drain traps kept filled with liquid. Drainpipes should be at least 4 in (10.2 cm) in diameter.

Walls should be smooth, moisture-resistant, nonabsorbent, resistant to impact damage, and free of cracks; they must be able to withstand cleaning with detergents, disinfectants, and high pressure water. For protection, they should have curbs, guardrails, bumpers, and corner guards.

Ceilings should be smooth, moisture-resistant, free of imperfect junctions, and able to withstand cleaning with detergents and disinfectants.

Heating, Ventilation, and Air-Conditioning (HVAC) should be designed for reliability, ease of maintenance and energy conservation. Relative humidity should be maintained at 30 - 70%, with a + 5% variation. The room’s intended use will determine whether positive or negative room pressure is required. Regular HVAC monitoring is best done at the individual room level.

Power and Lighting - The electrical system (HVAC, alternative power). All electrical fixtures must be properly sealed and haven protective covers. A time-controlled lighting system is necessary for a diurnal lighting cycle.

Storage areas should allow adequate space for bedding and food to be stored in a separate area. Corridors are inappropriate storage areas. Refuse storage areas should be separated from other storage areas. Refrigerated storage [below 7ºC (44.6ºF)] is used for temporarily storing dead animals.

Noise control measures should ensure that noise-producing functions are separated from housing and experiential areas, and that potential animal exposure to environmental monitoring alarm systems is minimized.

Facilities for Sanitizing Materials - Dedicated sanitization facilities, for sanitizing cages and other equipment, should be centrally located; considerations include ventilation, utilities, sound, insulation, traffic flow, and space.

Aseptic surgery facilities should be designed with the size of species to be used in mind. Traffic flow should be minimized. The areas should be easy to clean. Support areas should be separate from, but convenient to, surgical facilities to eliminate contamination of aseptic area. Recovery areas should provide the support needs required by the animals and be in clear view of staff. Filtered air should be supplied in surgical room.

III. The Animal Welfare Act (AWA)

The Animal Welfare Act is one of two main federal directives regarding the use of animals in research:

• Animal Welfare Act and Regulations Always applies if "covered/regulated" species involved:

• Laboratory Animal Definition (covered species): Any live or dead dog, cat, nonhuman primate, guinea pig, hamster, rabbit or any other warm blooded animal, which is being used or is intended for use for research, teaching, testing, experimentation, or exhibition purposes, or as a pet except birds, rats of the genus Rattus, and mice of the genus Mus bred for use in research.

• Health Research Extension Act and PHS Policy Applies only if research supported by federal funds

The Act itself is a law passed by Congress, and directs the United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) to administer and enforce the regulations. The particular service within APHIS that administers Federal laws concerning transportation, sale, and handling of animals used in laboratory research is REAC (Regulatory Enforcement and Animal Care).

The AWA specifies activities that must be regulated and addresses the perceived need for and intended effect of the mandated regulations. However, it does not provide details of the standards or regulations. The detailed standards and regulations of the Act are conceived, promulgated, and enforced by US Department of Agriculture (officially, the USDA Secretary). All proposed and final amendments to the standards and regulations are published in the Federal Register under the heading, Department of Agriculture, Animal and Plant Health Inspection Service. The rules and regulations for the AWA are published in the Code of Federal Regulations (CFR), Title 9, Animals and Animal Products, Subchapter A - Animal Welfare, Parts 1, 2, and 3.

An Abbreviated Summary of the Major Points for the Animal Welfare Act

An Abbreviated Summary of the Major Points for the Animal Welfare Regulations (Parts 1-3)

Part 1. Definition of Terms

This section defines specific terms that are used in parts 2 (regulations) and 3 (standards) of the AWA

Act:
The Act of August 24, 1966, commonly known as the Laboratory Animal Welfare Act. Amended by the Act of December 24, 1970, Act of April 22, 1976, and the Act of December 23, 1985.

Administrative Unit:
Means the organization or management unit at the departmental level of a research facility.

Animal:
Any live or dead dog, cat, nonhuman primate, guinea pig, hamster, rabbit or any other warm blooded animal, which is being used or is intended for use for research, teaching, testing, experimentation, or exhibition purposes, or as a pet except birds, rats of the genus Rattus, and mice of the genus Mus bred for use in research.

Attending Veterinarian:
A person who graduated from a veterinary school accredited by the American Veterinary Medical Association’s Council on Education, or has a certificate issued by the American Veterinary Medical Association’s Education Commission for Foreign Veterinary Graduates, or has received equivalent formal education.

Carrier:
The operator of an airline, railroad, motor carrier, shipping line, or other enterprise which engages in the business of transporting any animals for hire.

Cat:
Any live or dead cat (Felis catus) or any cat-hybrid cross.

Class "A" Licensee (breeder):
Person subject to the licensing requirements, meets the definition of a "dealer", and whose business involving animals consists only of animals that are bred and raised on the premises, in a closed or stable colony, and those animals acquired for the sole purpose of maintaining or enhancing the breeding colony.

Class "B" Licensee:
A person subject to the licensing requirements, meeting the definition of a "dealer", and whose business includes the purchase and/or resale of any animal.

Class "C" Licensee (exhibitor):
A person subject to the licensing requirements, meets the definition of an "exhibitor", and whose business involves the showing or displaying of animals to the public.

Commerce:
Trade, traffic, transportation, or other commerce

Committee:
The Institutional Animal Care and Use Committee

Dealer:
Any person who, in commerce, for compensation or profit, delivers for transportation, or transports, except at a carrier, buys, or sells, or negotiates the purchase or sale of any dog or other animal whether alive or dead for research, teaching, testing, experimentation, exhibition, or for use as a pet, or any dog for hunting, security, or breeding purposes.

Dog:
Any live or dead dog (Canis familiaris) or any dog-hybrid cross.

Exhibitor:
Any person exhibiting animals that were purchased in commerce or intended for distribution.

Euthanasia:
The humane destruction of an animal accomplished by a method that produces rapid unconsciousness and subsequent death without evidence of pain or distress.

Federal Award:
Any mechanism (including a grant, award, loan, contract, or cooperative agreement) under which Federal funds are used to support the conduct of research, experimentation, or testing, involving the use of animals.

Federal Research Facility:
Each department, agency, or instrumentality of the US which use live animals for research

Field Study:
A study conducted on free-living wild animals in their natural habitat. No invasive procedures are allowed.

Institutional Official:
The individual at a research facility who is authorized to perform a function under the AWA.

Intermediate Handler:
Any person engaged in business in which he receives custody of animals in connection with their transportation in commerce.

Licensed Veterinarian:
A person who has graduated from an accredited school of veterinary medicine or has received equivalent formal education as determined by the administrator, and who has a valid license to practice veterinary medicine in some State.

Major Operative Procedure:
Any surgical intervention that penetrates and exposes a body cavity or any procedure that produces permanent impairment of physical or physiological functions.

Nonconditioned Animals:
Animals which have not been subjected to special care and treatment for sufficient time to stabilize, and where necessary, to improve their health.

Nonhuman Primate:
Any nonhuman member of the highest order of mammals including prosimians, monkeys, and apes.

Painful Procedure:
Applied to any animal means any procedure that would reasonably be expected to cause more than slight or momentary pain or distress in a human being.

Person:
Any individual, partnership, firm, joint stock company, corporation, association, trust, estate, or other legal entity

Random Source:
Dogs and cats obtained from animal pounds or shelters, auction sales, or from any person who did not breed and raise them on his/her premises.

Research Facility:
Any school (above high school), institution, organization, or person that uses or intends to use live animals in research.

Sanitize:
To make physically clean and to remove and destroy, to the maximum degree that is practical, agents injurious to health.

Secretary:

Secretary of Agriculture of the United States or his representative.

Standards:
The requirements with respect to the humane housing, exhibition, handling, care, treatment, temperature, and transportation of animals by dealers, exhibitors, research facilities, carriers, intermediate handlers, and operators of auction sales.

State:
Includes all states, districts, territories or possessions of the USA.

Study Area:
Any building room, areas, enclosure, or other containment outside of a core facility or centrally designated or managed area in which animals are housed for more than 12 hours.

Wild Animal:
Any animal now or historically found in the wild, or in the wild state, within the boundaries of the USA, its territories, or possessions.

Part 2. Animal Welfare Regulations

USDA Registration

Non-federal research facilities and carriers are registered with the USDA. This registration must be renewed every 3 years; the registration form must be signed by the Institutional Official (IO). Dealers and exhibitors are licensed; this license is renewed annually.

Institutional Animal Care and Use Committee (IACUC)

The IACUC must be appointed by the Chief Executive Officer (CEO) of the research facility. It must consist of at least 3 people and must include:

• A chairperson;
• A veterinarian with training or experience in lab animal science and medicine; and
• A person unaffiliated with the facility and not related to an affiliated person to represent the general community.

There may be no more than 3 members from the same department.

IACUC Functions

• Semiannually inspect all animal facility areas, including study areas.
• Prepare reports from the inspections, citing deficiencies and plans for correction.
• Review and investigate public and employee concerns about animal care and use and noncompliance.
• Make recommendations to the IO regarding the research facility’s animal program; the IO is the one authorized to implement the IACUC’s recommendations.
• Review and approve animal use protocols annually, plus major changes to protocols.
• If necessary, may suspend an animal use protocol.

Attending Veterinarian

Every facility must employ an attending veterinarian under formal arrangements. The attending vet must have authority to ensure adequate veterinary care and oversee other aspects of animal care and use; he/she (or a vet that he/she designates) must be a voting member of the IACUC.

Animal Acquisition

AWA regulations establish licenses and requirements for animal vendors and carriers transporting animals. Dealers must be licensed by the USDA.

Dealers are licensed as Class A (raise and sell purpose-bred animals) or Class B (provide random-source animals).

Pounds or shelters must hold any live dog or cat for at least 5 days (including a Saturday, not including the day of arrival and transit time) before supplying the animal to a Class B dealer.

The purpose is to allow owners the opportunity to retrieve lost animals. Research facilities that obtain dogs or cats from sources other than dealers, exhibitors, and persons exempt from licensing regulations must also hold animals for 5 days (not including the day of arrival and transit time).

Animal Identification

All live dogs or cats must be properly identified at the time of acquisition, transportation, sale or disposal. If a tag and collar is used, the collar must fit well and be made of materials acceptable to pet owners.

An official tag must have "USDA", the number/letters identifying the state and dealer, and a unique animal number on it. Tags cannot be reused within a 5- year period and must be held for 1 year after final disposition of the animal. An alternative to using a tag and collar is a distinctive and legible tattoo marking approved by the USDA.

When one or more animals are shipped in a primary enclosure, there must be a label attached stating the species, the number of animals, distinctive physical features, and identifying marks, tattoos, or tags attached to the animals.

Health Certificates

Any dog, cat, or nonhuman primate transported by a research facility must be accompanied by a health certificate issued by a vet stating:

• The vet examined the animal no more than 10 days prior to transportation; and
• The animal appeared to be free of any infectious disease or physical abnormality which would be a danger to the animal itself, other animals, or people.

Facility Records

Records mandated by USDA are open to USDA inspection and must be kept by the facility for at least 3 years except animal use protocols, which must be kept for 3 years following completion of the activity.

IACUC Records

• Minutes of the IACUC meetings
• Animal use protocols and significant changes
• Semiannual reports and recommendations

Records for Live Dogs, Cats and Offspring

• The name, address, and USDA number of the person from whom animals were purchased (if person is not licensed, their delivery vehicle license number, state and driver’s license) number and state must be recorded
• The date of acquisition of the animal
• The animal’s official USDA tag/tattoo number
• A detailed description of the animal (includes the same information as a health certificate plus any number or mark applied by the facility)
• The animal’s health certificates (if available)
• Certification from the dealer for random source dogs and cats
• A record of disposition
• The name and address of person to whom the live dog or cat is transported, sold, or otherwise disposed of
• The date of transportation, sale, euthanasia, or other disposition of the animal
• The method of transportation, including the name of the initial carrier or intermediate handler (the name of the vehicle owner is required if a privately owned vehicle is used)

Health Records are intended to demonstrate adequate veterinary care and should include:

• Animal identity
• A description and resolution of problems, such as illness, injury, etc.
• The dates and details of observations, tests, treatments, procedures, etc.
• Treatment plan with diagnosis and prognosis

Annual Report

The annual report must be signed and filed by the IO on or before December 1 of each year. The report must assure that:

• The facility is adhering to the AWA standards and regulations.
• Professionally acceptable standards are used in the animal care and use program.
• Principal investigators have considered alternatives to painful procedures.

The report must include a detailed account of animal usage with regard to the following pain categories:

• B: Animals bred, conditioned or held for use in teaching, testing, research, but not yet used for such purposes
• C: Procedures with no or transient pain or distress (e.g., injections, blood draw)
• D: Painful/distressful procedures for which anesthetics, analgesics, or tranquilizers are given
• E: Procedures with pain or distress for which drugs to relieve the pain/distress would have adversely affected the research study (scientific justification must be given in the report

Part 3. Animal Welfare Regulation Standards

Part 3 of the Animal Welfare Act Regulations specifies standards for the humane handling, care, treatment, and transportation of dogs, cats, guinea pigs, hamsters, rabbits, nonhuman primates, marine mammals, and other warm-blooded animals.

This synopsis will first describe general features of housing that apply to all covered species. Then, standards for specific species are summarized. Tables specific cage size can be found in the Animal Welfare Act Regulations.

You should refer directly to the Animal Welfare Act Regulations if:

• Your job involves decision-making on husbandry practices in an animal facility. Detailed standards are excluded from this lesson.
• Your job involves shipping animals via commercial carriers. The lesson excludes transportation standards for carriers and intermediate handlers.

General (general practices that apply to all covered species)

AWR Standards: General Practices - All Covered Species

The primary enclosure should:

• Be structurally sound and in good condition
• Prevent animals from escaping and others from entering
• Protect from injury
• Be easily sanitized
• Contain no sharp points that could injure animals
• House juveniles separate from adults, except for the dam while nursing
• Provide minimum floor space (excluding food/water receptacles) for given species as defined in the sections to follow.

The housing facilities must have the appropriate utilities (such as power and water) to meet husbandry requirements. Food and bedding should be stored in a manner that prevents damage from moisture and mildew. Outdoor facilities should provide sufficient shelter to protect animals from wind, sun, heat, cold, and precipitation. All facilities should have adequate drainage and waste disposal.

Building and grounds must be kept in good repair to protect animals from injury and facilitate required husbandry practices. An effective program for control of insects, external parasites, and all pests must be maintained.

Group-housed animals must be compatible with each other. Animals should be observed for signs of aggression and fighting, and separated accordingly.

Different animal species should not be housed together in the same primary enclosure. Incompatible animal species should not be mixed in the same animal room.

For example, rabbits or cats should not be housed where they can hear dogs barking. Rabbits and guinea pigs should not be housed together, due to the risk of transmissible infections.

Animals that have, or are suspected of having, a contagious disease must be isolated from healthy animals in the colony, as directed by the attending veterinarian. When an entire group of animals is exposed to an infectious agent, the group may be kept intact during the process of diagnosis, treatment, and control.

The AWA Regulations describe standards and methods for cleaning and sanitizing primary enclosures and food/water receptacles.

Ventilation must be adequate to control relative humidity and minimize odors, drafts, ammonia levels, and moisture condensation. Animals must be maintained at temperatures to which they are suited and acclimated. Animals that are sick, aged, or very young should have more restricted temperature ranges to protect their health and well-being.

Indoor lighting must be adequate and uniform for the well-being of the animals, and to permit routine inspection of the facilities, cleaning of the facility, and observation of the animals. Animals must be protected from exposure to excessively bright lights. A regular diurnal lighting cycle of either natural or artificial light must be provided.

Animals must be fed at least once daily, except as may be required to provide adequate veterinary care. Food must be stored under appropriate conditions to prevent deterioration in its nutritive value. Food receptacles must be kept clean and sanitized at least every 2 weeks.

Water must be clean, palatable, and free of contaminants. If water is not accessible to the animals at all times, then water must be offered at least twice daily for at least 1 h each time. Water receptacles must be cleaned and sanitized at least every 2 weeks.

Food or water restriction is permissible for research studies, provided that the project is approved by the IACUC and that professional standards for animal welfare are observed.

General Husbandry and Facilities

All outdoor housing facilities must be enclosed by a perimeter fence that is of sufficient height to keep out animals and unauthorized persons. One exception to this rule is where the outdoor housing facility houses only farm animals.

Animals housed in the same primary enclosure must be compatible. Animals shall not be housed near animals that interfere with their health or cause them discomfort.

Transportation

Carriers shall not accept any live animals for shipment more than 4 h prior to the scheduled departure. If a mutual agreement is made in advance, this time may be extended to not more than 6 h.

Any carrier or intermediate handler shall only accept animals with a signed certificate that includes all of the following:

• The name and address of the consignor;
• The number of animals in the primary enclosure(s);
• A certifying statement [e.g., "I hereby certify that the __ (number) primary enclosure(s) which are used to transport the animal(s) in this shipment complies (comply) with USDA standards for primary enclosures (9 CFR part 3)."]; and
• The signature of the consignor and the date.
  Carriers shall attempt to notify the consignee at least once in every 6-h period following the arrival of the animal. The time, date, and method of each attempted notification, the final notification to the consignee, and the name of the person notifying the consignee shall be recorded.

Transportation Enclosures - In addition to general requirements for primary housing enclosures, transport cages and crates must be constructed in such a manner that the structural strength of the enclosure is sufficient to contain the live animals and to withstand the normal rigors of transportation.

It should include handholds to allow persons to lift without tilting and to ensure that the person handling the primary enclosure will not be in contact with the animal. The cage design should permit animals to be easily and quickly removed from the enclosure in an emergency.

Primary enclosures used to transport live animals must be large enough to ensure that each animal contained therein has sufficient space to move freely and to make normal postural adjustments.

The cage or crate must have a solid bottom to prevent leakage, and must be designed so that the animal cannot extend any part of its body outside the enclosure; otherwise, it may cause injury to itself or to persons or animals nearby.

Animals must be provided with proper ventilation in transit. The transport cages must allow sufficient airflow between adjacent cages, and crates must have sufficient ventilation openings. These openings can be located on two opposite walls of the primary enclosure; the openings on each wall must comprise at least 16% of the total surface area of the wall.

Live animals transported in the same primary enclosure shall be of the same species and maintained in compatible groups. No female animal in estrus shall be transported in the same primary enclosure with any male animal.

Primary enclosures used to transport live animals shall be clearly marked on top and on one or more sides with the words "Live Animal" or "Wild Animal" in letters no less than 2.5 cm (1 in.) high, and with arrows or other markings to indicate the correct upright position of the container.

Terminal Facilities - Auxiliary ventilation such as exhaust fans, vents, fans, blowers, or air conditioning shall be used for any animal holding area containing animals when the air temperature within the holding area is 23.9ºC (75ºF) or higher.

The air temperature around any live animal in any animal holding area shall not be allowed to fall below 7.2ºC (45ºF) or exceed 29.5ºC (85ºF) at any time. No animal shall be subjected to surrounding air temperatures that exceed 23.9ºC (75ºF) for more than 4 h at any time.

Carriers whose facilities fail to meet the minimum temperature may accept animals for transportation if the animal is accompanied by a certificate signed by an accredited veterinarian not more than 10 days prior to delivery certifying that the animal(s) in the shipment are acclimated to air temperatures lower than 7.2ºC (45ºF).

Handling - Transport cages or crates must be cleaned and sanitized before each use. When sunlight is likely to cause overheating or discomfort, sufficient shade shall be provided to protect the live animals from the direct rays. In this circumstance, animals shall not be subjected to surrounding air temperatures that exceed 29.5ºC (85ºF) for longer than 45 min.

Transporting devices shall be covered to provide protection for live animals when the outdoor air temperature falls below 10ºC (50ºF). Animals shall not be subjected to surrounding air temperatures that fall below 7.2ºC (45ºF) for a period of more than 45 min unless such animals are accompanied by a certificate of acclimation.

All animals must be offered potable water within 4 h prior to being transported. Once travel is initiated, animals must be provided water at least every 12 h. Each animal shall be fed at least once in each 24-h period. A sufficient quantity of food and water shall accompany live animals to sustain such animals for a period of at least 24 h.

Animals must be observed during surface transportation at least once every 4 h to assure health and well-being. When transported by air, animals must be visually observed not less than once every 4 h, unless the animal cargo space is not accessible during flight, in which case the animal must be observed whenever loaded and unloaded.

Dogs and Cats

Indoor facilities must be sufficiently heated and cooled to protect animals from temperature extremes and provide for their health and well being.

The ambient temperature must not fall below 45ºF or rise above 85ºF for more than four consecutive hours when animals are present.

Excreta and food waste must be removed (spot cleaned) from primary enclosures daily and from under primary enclosures as often as necessary to prevent an excessive accumulation of feces and food waste. Primary enclosures should be sanitized at least every 2 weeks.

The primary enclosure space for dogs (including weaned puppies) must have a minimum interior height of at least 6 in. higher than the head of the tallest dog in the enclosure when it is in a normal standing position. The minimum amount of floor space is calculated as follows:

(L+6)2/144 = minimum space in square feet

where L = the length of the dog in inches from the tip of its nose to the base of its tail. Breeding bitches will need additional floor space, per the recommendations of the attending veterinarian. (These requirements differ from the Guide, which bases the minimum required space on the weight of the dog.)

All facilities, including dealers and exhibitors, must develop, document, and follow an appropriate plan to provide dogs with the opportunity for exercise.

Dogs that are housed in a primary enclosure that is twice their required floor space are exempt, as are multiple-housed dogs with 100% of the required floor space per dog.

Dogs may be exempt from the exercise program by the attending veterinarian based on concerns for their health or well-being. This exemption, unless permanent, must be reviewed by the attending veterinarian every 30 days.

Primary enclosures for cats must have an elevated resting board(s) large enough to accommodate all the cats in the enclosure at the same time. Low boards that do not allow cats to comfortably occupy the space beneath them are not considered elevated and are instead counted as part of the minimum floor space.

Guinea Pigs and Hamsters

Ambient temperature for indoor housing facilities must not be allowed to fall below 60ºF nor to exceed 85ºF. Outdoor facilities are not suitable for hamsters; approval must be obtained from the USDA to house guinea pigs outdoors. Guinea pig and hamster enclosures must be cleaned and sanitized at least every 2 weeks.

Rabbits

Indoor facilities do not need to be heated. If housed outdoors, artificial cooling (e.g., a sprinkler system) must be provided when the outside temperature exceeds 90ºF; shelter must be provided when outside temperatures fall below 40ºF. Rabbits should be protected from sunlight, rain, cold, and predators. No more than 15 live rabbits shall be transported in the same primary enclosure.

Primary enclosures for rabbits must be sanitized at least once every 30 days and when introducing a rabbit into a previously used cage. (The Guide recommends that slotted-floor cages and cage racks be sanitized every 2 weeks.)

Enclosures shall be kept reasonably free of excreta, hair, and other debris. If cage floors are wire or mesh, the underlying troughs or pans must be cleaned at least once a week. Food and water receptacles shall be sanitized at least once every 2 weeks.

Nonhuman Primates

Indoor housing facilities must be sufficiently heated and cooled to protect nonhuman primates from temperature extremes and to provide for their health and well-being. The facility’s ambient temperature must not fall below 45ºF (7.2ºC) or rise above 85ºF (29.5ºC) for more than four consecutive hours.

Outdoor housing is permissible as long as the particular species can tolerate the range of temperatures and climatic conditions known to occur at that facility at that time of year. Outdoor shelters must be sufficiently large to provide protection comfortably to each nonhuman primate housed in the facility.

When there are aggressive or dominant animals housed with others, multiple shelters must be provided to ensure that each animal has access to shelter. The outdoor area of a sheltered housing facility must be enclosed by a fence that is of sufficient height (6 ft), construction, and distance (3 ft) from the primary enclosure to keep out unwanted species and unauthorized persons.

Excreta and food waste must be removed from primary enclosures daily and from under primary enclosures as often as necessary to prevent an excessive accumulation of feces and food waste. Primary enclosures must be sanitized at least every 2 weeks.

The minimum space provided to each animal, whether housed individually or with others, is based on the typical weight of animals of its species.

Brachiating species and great apes are grouped separately because they require additional space to engage in species-typical behavior. Prosimian species vary in weight and should be grouped with their appropriate weight group. Infants and juveniles of certain species are substantially lower in weight than adults of those species and require the minimum space requirements of lighter-weight species, unless the animal is obviously unable to make normal postural adjustments and movements within the primary enclosure.

The six groups are:

• Group 1 - marmosets, tamarins, and infants (less than 6 months of age) of various species.
• Group 2 - capuchins, squirrel monkeys and similar size species, and juveniles (6 months to 3 years of age) of various species.
• Group 3 - macaques and African species.
• Group 4 - male macaques and large African species.
• Group 5 - baboons and nonbrachiating species larger than 33 lb (15 kg).
• Group 6 - great apes over 55 lb (25 kg) and brachiating species.

Research facilities must develop, document, and follow a plan for environmental enhancement to promote psychological well-being of nonhuman primates. The plan must be as directed by the attending veterinarian and in accordance with currently accepted professional standards. Specific provisions must be made to address the social needs of species known to live in social groups in nature. The physical environment in the primary enclosure must be enriched by providing noninjurious means of expressing species-typical activities.

Nonhuman primates must not be maintained in restraint devices unless required for health reasons as determined by the attending veterinarian or by a research proposal approved by the facility’s IACUC.

Exemptions to the environmental enrichment program are allowed. The attending veterinarian may exempt an individual animal from participation in the program for reasons of its health, condition, or well-being.

The basis for the exemption must be recorded by the veterinarian and, unless the condition is permanent, must be reviewed at least every 30 days by the veterinarian.

Marine Mammals

Since these mammals are not commonly seen in laboratory animal medicine, this section has been omitted. Refer to the standards for a comprehensive review.

IV. The Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals

The Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals was revised following passage of the Health Research Extension Act of 1985 (PL 99-158). That act required the Secretary of Health and Human Services, acting through the Director of NIH, to establish guidelines for the proper care and treatment of animals used in research, including the appropriate use of tranquilizers, analgesics, anesthetics, paralytics, and euthanasia, appropriate pre-surgical and post-surgical veterinary medical and nursing care, and the organization and operation of animal care committees. The Policy is intended to implement the "US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training".

The Policy applies to all PHS-conducted or supported activities involving animals regardless of where they are conducted. The PHS interprets this to include laboratories but institutions have discretion in how to assure compliance in these sites. Typically, most academic institutions have made the decision to apply these rules to all research regardless of the source of funding.

Laboratory Animal Definition: Any live, vertebrate animal (cold- or warm-blooded) used or intended for use in research, training, or testing. Avian species are covered only after hatching.

An Abbreviated Summary of the Major Points for the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals

I. Introduction

The PHS requires institutions to establish and maintain proper measures to ensure the appropriate care and use of all animals involved in activities conducted or supported by the PHS.

II. Applicability

This Policy is applicable to all PHS-conducted or -supported activities involving animals, regardless of where the activities are performed. All institutions are required to comply with the AWA, and other Federal statutes as necessary.

III. Definitions

Definitions pertaining to PHS Policy are found within the original document.

Note that the definition of "animal" differs from that in the AWA. For the purposes of this Policy, "animal" refers to any live vertebrate animal. This is a stricter definition than that under the AWA, which excludes rats, mice, and birds.

IV. Implementation by Institutions

A. Animal Welfare Assurance

Institutions receiving PHS support must submit to the Office of Laboratory Animal Welfare (OLAW), formerly the Office of Protection from Research Risks (OPRR), a written Assurance setting forth compliance with this Policy prior to conducting any supported activities involving animals.

1. The Assurance shall fully describe the institution’s program for the care and use of animals, based on the Guide. The Assurance must be submitted every 5 years.
2. The institution must assure that it falls under one of the following categories:

• Category 1: Accredited by AAALAC International. All programs and facilities must also be evaluated every 6 months by the IACUC.
• Category 2: Evaluated by the Institution. All programs and facilities are evaluated by the IACUC every 6 months. The most recent report is to be submitted with the Assurance.

3. The Assurance must include the names, position titles, and credentials of the IACUC chairperson and members. The committee shall consist of not fewer than 5 members, including one veterinarian with experience in lab animal medicine, one scientist with experience in animal research, one nonscientific member, and one individual who is not affiliated with the institution. An individual may fulfill more than one of these roles.

B. Functions of the Institutional Animal Care and Use Committee

According to the PHS Policy, the IACUC shall:

• Review the institution’s animal use program and inspect all animal facilities every 6 months using the Guide as a basis for evaluation. An animal facility is any building, room, area for confinement, transport or experiments (including surgery) where animals are maintained for >24 h.
• Prepare reports based on evaluations, and submit them to the IO every 6 months; these reports must be made available to OLAW upon request. The reports must distinguish between minor and significant deficiencies. Significant deficiencies pose a threat to animal health and/or safety.
• Review and approve, require modifications in, or withhold approval of activities related to the care and use of animals.
• Be authorized to suspend an activity involving animals.

C. Review of PHS-Conducted or -Supported Research Projects

1. The IACUC shall review all components of proposed research projects and significant changes to ongoing research projects to determine that they are in accordance with this Policy. The IACUC shall also determine that the project conforms with the institution’s Assurance and meets the following requirements:

• Procedures will avoid or minimize discomfort, distress, and pain to the animals.
• Appropriate sedation, analgesia, or anesthesia will be provided as needed unless scientifically justified not to do so.
• Medical care will be provided by a qualified veterinarian.
• Research personnel will be appropriately qualified and trained to perform any procedures relating to animals.
• Methods of euthanasia will be consistent with the AVMA Panel on Euthanasia.

2. Prior to review, each IACUC member shall be provided with a written description of research projects that involve animals. At least one member of the IACUC shall review each project, and any member can request a full committee review of any project. No member who has a conflicting interest may contribute to the constitution of the quorum (or majority in attendance).
3. The IACUC may invite consultants to assist in the review of complex issues.
4. The IACUC shall notify investigators and the institution in writing of its decision to approve or disapprove a protocol or withhold approval of animal related activities. All protocols must be reviewed every 3 years.
5. The IACUC may suspend any previously approved activity if it is determined that the activity is not being conducted in accordance with the AWA, the Guide, the Assurance of the institution, or this Policy. Suspension can only occur after there has been a convened IACUC meeting with a quorum present.
6. If the IACUC suspends an activity, the IO and the IACUC shall review the reasons, take appropriate action, and report to OLAW.

D. Information Required in Applications and Proposals for Awards Submitted to PHS

1. Identification of species and approximate numbers to be used
2. Rationale for using animals, and appropriateness of numbers and species
3. Complete description of proposed animal use
4. Description of measures to assure that discomfort to animals will be limited to that which is unavoidable in the conduct of scientifically valuable research
5. Description of euthanasia methods

E. Record-Keeping Requirements

1. The institution shall maintain:

1. A copy of the Assurance
2. Minutes of IACUC meetings
3. Records of applications
4. Proposals and proposed significant changes
5. Whether IACUC approval was given or withheld
6. Records of semiannual IACUC reports
7. Records of accrediting body determinations

2. All records must be maintained for at least 3 years after the completion of the approved activities.

F. Reporting Requirements

1. At least every 12 months, the IACUC, through the IO, shall report to OLAW:

1. any facility or program changes that would place the institution in a different category than stated in its Assurance
2. any changes to program description or changes in IACUC membership
3. notice of the dates that the IACUC conducted its semiannual evaluations

2. The IACUC, through the IO, shall provide OLAW with an explanation of circumstances and actions taken with respect to:

1. any serious or continuing noncompliance with this Policy
2. any serious deviation from the provisions of the Guide
3. any suspension of an activity by the IACUC

3. Reports must contain any minority views filed by IACUC members.

V. Implementation by PHS

OLAW is responsible for the general administration and coordination of this Policy.

Any institution receiving PHS funds is subject to review at any time by PHS staff.

V. Good Laboratory Practice Regulations (GLPs)

The purpose of the Good Laboratory Practices (GLP) regulations are to ensure the quality and integrity of data submitted pursuant to:

1. Testing consent agreements and test rules under the Toxic Substances Control Act (TSCA) [Code of Federal Regulations; Title 40, Part 792].
2. Support for research/marketing permits to the FDA for products regulated by the Federal Food, Drug, and Cosmetic Act and Public Health Service Act [Code of Federal Regulations; Title 21, Part 58].
3. Support for research/marketing permits for pesticide products regulated by the Environmental Protection Agency pursuant to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug and Cosmetic Act (FFDCA) [Code of Federal Regulations; [Title 40, Part 160].

To this end, most of the requirements are considered familiar and reasonable by any conscientious scientist. Protocols and standard operating procedures (SOPs), adequate facilities and equipment, full identification of test substance, proper animal care, equipment maintenance, accurate recording of observations, and accurate reporting of results are basic necessities for the conduct of a high-quality, valid toxicity, or any scientific study. The regulations also place a heavy emphasis on data recording and record and specimen retention to ensure that a study could be reconstructed at a later time if the need arose.

The regulations go beyond these basic requirements for a valid study by requiring each study to have a study director, who would have "ultimate responsibility for implementation of the protocol and conduct of the study", and each testing facility to have a quality assurance unit to monitor conduct of studies. The concept of a quality assurance unit to monitor study conduct was a new one to most laboratories but a familiar one in manufacturing facilities operating under various good manufacturing practice regulations.

Each agency has its own guidelines that outline similar practices. For simplification, this brief summary will incorporate main ideas found within these three GLPs.

An Abbreviated Summary of the Major Points for the Good Laboratory Practice Regulations (GLPs)

Definitions

Batch:
Specific quantity or lot of a test, control, or reference substance

Carrier:
Any material with which the test substance is combined for administration (e.g., food, water, etc.)

Control substance:
Any substance or material administered to provide a basis for comparison with the test substance

EPA:
Environmental Protection Agency

FDA:
The USA Food and Drug Administration

FFDCA:
The Federal Food, Drug and Cosmetic Act

FIFRA:
The Federal Insecticide, Fungicide and Rodenticide Act

Raw data:
Any worksheets, records, notes or copies that are the results of original observations and activities of a study. May also include photos, computer printouts, dictated observations, and recorded data from automated instruments.

Specimen:
Any material derived from a test system for examination or analysis

Sponsor:
Person or facility that initiates and supports a study

TSCA:
The Toxic Substances Control Act

Test system:
Any animal, plant, microorganism, etc. to which a substance is administered for study

Inspection of Testing Facilities - Testing facilities are subject to inspection by FDA or EPA, and must supply all information desired by the inspectors.

Organization and Personnel

Personnel conducting studies must be trained, and records of job experience must be maintained. There shall be a sufficient number of personnel, and they should take appropriate personal sanitation measures and wear appropriate clothing for their duties.

Testing Facility Management - A study director shall be designated, as must a quality assurance unit. They must assure that the substances are properly tested.

The study director has overall responsibility for the technical conduct of the study, and for the interpretation / reporting of results. They must ensure that all testing systems and data are recorded and verified, that anything potentially affecting the quality of the study be noted, and that GLP standards are followed.

The quality assurance unit is responsible for monitoring each study to assure management that the facilities, personnel, methods and records are in conformance with GLP standards. The quality assurance unit must maintain copies of all protocols and conduct inspections of each study to ensure the integrity of the study.

Facilities

Test System Care Facilities - A testing facility shall have a sufficient number of animal rooms to ensure proper separation of species and isolation of individual projects.

There should be separate areas for the diagnosis, treatment, and control of test system diseases. The facility must have provisions for the collection and disposal of contaminated water and animal waste.

Test System Supply Facilities - There shall be storage areas for feed, bedding, supplies, and equipment.

Required Areas - Facilities shall be provided for the receipt, storage and mixing of test, control, and reference substances. In addition, space shall be provided for conducting procedures and storing raw data (with limited access to the latter).

Equipment

Equipment shall be of appropriate design and adequate capacity to conduct the study.

Maintenance and Calibration - Equipment shall be adequately calibrated and maintained with written records.

Testing Facilities Operation

Standard Operating Procedures shall be written for all procedures involving the study, including care of the animals. Animals must be identified at least to the cage level. Animals removed from their housing units for manipulation must have individual identification.

Reagents and Solutions - All reagents and solutions must be labeled as to the identity, concentration, storage requirements, and expiration date. Anything out of date should be disposed of properly.

Animal and Other Test System Care - Standard operating procedures for the housing, feeding, and care of animals must be maintained. Any new animals must be quarantined and acclimated prior to use. All animals must be identified appropriately and housed separately when necessary. All housing areas must be kept clean and sanitized.

Test, Control, and Reference Substances

Substance Characterization, Handling, and Mixing - Each batch of substances must be tested to ensure quality and must be properly stored and labeled.

Protocol for and Conduct of a Study

Each study must have an approved written protocol that states all the objectives and methods for the conduct of the study. The study shall be conducted in accordance with the protocol. All animal specimens must be identified by test system, study, nature and date of collection. Any changes in data entry must not obscure the original entry; a reason for the change must be stated, and shall be dated and signed at the time of change. This is also true for automated data entries, except that instead of a signature, the responsible individual shall be identified.

Records and Reports

The final report must include, but is not limited to, the objectives, methods, results, and storage information for the raw data. The study director must sign the final report for a study, and a statement must be prepared and signed by the quality assurance unit. The sponsor and the test facility maintain a copy of the final report. All raw data, records, specimens, and final reports from a study are retained. Such archives must have limited access and must be maintained for at least 5 years following the date on which the results of the study are submitted to the agency. Wet specimens (e.g., blood, urine) do not need to be retained after quality assurance verification.

VI. The AAALAC Accreditation Program

What is The AAALAC?

AAALAC, (now the Association for Assessment and Accreditation of Laboratory Animal Care International, Inc.) is a private nonprofit organization that was spun out of the American Association for Laboratory Animal Science (AALAS) in 1965. AAALAC is guided by a Board of Trustees comprised of representatives of 41 scientific, professional, and educational member societies. The Council on Accreditation is the core of AAALAC and operates the accreditation program.

Why is AAALAC accreditation important?

Accreditation through AAALAC is voluntary, and demonstrates a willingness to go above and beyond the minimums required by law. An accredited facility is in full compliance with the Guide and all government policies and regulations. There are currently 650 units accredited.

It represents quality - Organizations and companies look for ways to communicate their commitment to excellence. In the scientific community, AAALAC accreditation shows that an institution is serious about setting, achieving and maintaining high standards for animal care and use. Around the world, AAALAC accreditation is recognized as a symbol of quality.

It promotes scientific validity - When scientific research involves animals, reliable results depend on superior animal care. AAALAC accreditation engages scientists, managers and administrators in an independent, rigorous assessment of their institution's animal program--an assessment that ultimately results in better research practices and outcomes.

It provides a confidential peer-review - Accreditation requires an institution to first perform its own self-evaluation (an extremely valuable management exercise). Next, a team of highly qualified professionals provides a confidential, on-site evaluation of the institution's animal care and use program. The independent review assures management that the research program is maintaining high standards. The assessment also helps them learn how they can achieve even higher levels of good animal care and quality research.

It impresses funding sources and research partners - Many private biomedical organizations, including the American Heart Association and the Cystic Fibrosis Foundation, strongly recommend that grantees using animals in their studies be part of an AAALAC-accredited program. Government agencies such as NIH, NASA, the Department of Defense, Veterans Affairs and the National Science Foundation see AAALAC accreditation as a commitment to program excellence. Both private and public funding sources view accreditation as an assurance that animal use will be justified and humane, and that appropriate regulations and policies will be followed.

Who can apply for accreditation?

Any private or public institution, organization, or agency maintaining, importing, breeding, or using animals in research, teaching, or testing may apply for accreditation.

An active animal care and use program must be operational prior to applying for accreditation

The Site Visit

Site visits to all applicants are conducted a member of Council and one or more ad hoc consultants; revisits are scheduled within three years. Site visitors rely on the Guide for the Care and Use of Laboratory Animals, National Academy Press, Washington, D.C., 1996, as the primary source of guidelines.

The site visitors conduct an exit briefing to present their preliminary findings and impressions.

Following the site visit, the site visitors prepare a written evaluation of each site visit for submission to the Council on Accreditation. Council meets three times per year to formally review reports. The unit is notified in writing of its accreditation status, usually within two months of the Council meeting.

Accredited units must submit an annual report. All reports and communications with the unit are kept confidential.

AAALAC Categories of Accreditation

Full Accreditation - New applicants with animal care and use programs that conform with AAALAC International standards are awarded full accreditation.

Provisional Accreditation - New applicants that do not meet AAALAC standards but, in the opinion of Council, have deficiencies that can be corrected within a period not longer than 24 months, are awarded Provisional Accreditation.

Provisionally accredited units actively participate in the AAALAC accreditation program, but are not considered AAALAC accredited. At the conclusion of the provisional period, the unit must either achieve Full Accreditation or accreditation is withheld.

Withhold Accreditation - Accreditation is withheld from new applicants if, in the opinion of Council, deficiencies in the animal care and use program are so extensive that there is little likelihood that full accreditation could be achieved within 24 months. These deficiencies usually involve major program issues and/or physical plant concerns.

Continued Full Accreditation - Following a site revisit, accredited units that continue to conform with AAALAC standards are awarded Continued Full Accreditation.

Deferred Continued Accreditation - If the site revisit to a full accredited unit reveals serious but short-term, correctable deficiencies in its animal care and use program, Deferred Continued Accreditation is awarded. A two month period is allowed for fully correcting deficiencies identified in the written report. Unsatisfactory or non-correction of the identified deficiencies in the allotted time will result in probationary accreditation for a period of six months from the date of deferred continued accreditation.

Probationary Accreditation - A fully accredited unit is placed on probation if the site revisit reveals that serious but correctable deficiencies have developed. Probation may be extended for up to 12 months to allow for sufficient time to fully correct deficiencies while maintaining accreditation. At the end of that period, the unit must fully correct deficiencies and achieve Continued Full Accreditation, or accreditation is revoked.

Revoke Accreditation - At the time of a site revisit or at the end of a probationary period, accreditation may be revoked if serious deficiencies in the animal care and use program exist. If the deficiencies are subsequently corrected, the unit may reapply for accreditation as a new applicant.

VII. Acknowledgments

Portions of this chapter were developed for: Laboratory Animal Regulatory Workbook, 2nd Edition, American Association for Laboratory Animal Science (AALAS). I would like to acknowledge the efforts of Deborah Caruso, Dr. Jennifer Pullium, Traci Reddick, and Dr. Peter Smith for help in preparing guideline summaries. I would also like to thank Dr. Mark Suckow for editorial review.