Rev. 7/26/2005
This training course is designed to provide an overview of the following aspects of animal research: o Regulation of the use of animals in research and teaching o Ethics of research o The role of the IACUC o The process of protocol development and review o Occupational Health and Safety of individuals who care for and use research animals.
REGULATION OF THE USE OF ANIMALS IN RESEARCH AND TEACHING
United States Department of Agriculture (USDA)
Congress gave the USDA broad authority to regulate animal research in the Animal Welfare Act .
The USDA then established the USDA Animal Welfare Act Regulations, and a Policy Manual .
The definition of an animal given in the regulations is as follows:
" Animal means 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.”
This term excludes: Birds, rats of the genus Rattus, and mice of the genus Mus, that are specifically bred for research.
The Public Health Service (PHS)
Passed by Congress in 1985, the Health Research Extension Act directed PHS to provide guidelines for animal research.
The Office of Laboratory Animal Welfare (OLAW) is responsible for monitoring institutional compliance with PHS policy and guidelines. OLAW relies primarily on two documents. o PHS Policy on Humane Care and Use of Laboratory Animals . It incorporates nine
U.S. government Principles for the Utilization And Care of Vertebrate Animals Used in Testing, Research and Training . o Guide for the Care and Use of Laboratory Animals (usually called the Guide ).
Compliance with PHS Policy is a required condition for receiving PHS support (federal funding) for activities involving vertebrate animals. PHS agencies include the National Institutes of Health
( NIH ) , the Centers for Disease Control and Prevention ( CDC ), and the Food and Drug
Administration ( FDA ).
PHS Policy covers all vertebrate species used for research, teaching, and testing, including rats, mice and birds. This is in contrast to the USDA AWA Regulations and Standards, which are not currently applied to laboratory mice and rats, birds, fish and animals used for agricultural research.
The Association for Assessment and Accreditation of Laboratory Animal Care,
International, or "AAALAC", is a non-profit organization that accredits animal facilities.
Institutions participate in the AAALAC accreditation program by voluntarily submitting to AAALAC site visits every three years. AAALAC accreditation has now become an accepted standard for quality animal research programs. The Animal Care and Use Program at Carolinas Medical
Center has been continuously accredited by AAALAC since 1993.
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Rev. 7/26/2005 General Training Course For Use Of Animals at Carolinas Medical Center
ETHICS OF RESEARCH
The Privilege of Conducting Animal Research
By law , an institutional committee must review all aspects of the animal care and use program.
The "Institutional Animal Care and Use Committee" (IACUC) protects both the individual investigator and the institution, while insuring that animal research is being performed in an ethical manner. Research utilizing animals is a privilege, not a right . The entire system is built on trust. However, a single incident of serious noncompliance with animal welfare regulation or guidelines can jeopardize all of the institution's privilege of conducting animal research.
By law, t he Three “R’s” must be considered when developing a project o Replacement of the use of animals with non-animal techniques, such as Computer models, cell or tissue culture systems, In vitro assays, inanimate surgical training. o Reduction of the number of animals used. Examples include: Limiting group sizes to the minimum needed to obtain statistically significant data, sharing tissues with other investigators and optimal design of experimental groups. o Refinement of the techniques or procedures used on animals, such as changing experiments or procedures to reduce pain or distress.
What About a Fourth "R" ?
o
Carolinas Medical Center promotes a fourth R, for Respect . This entails the respectful treatment of animals and their physiological and psychological needs.
What are the major responsibilities of the animal user? o To perform procedures only as described in the protocol form and authorized by the
IACUC. If modifications are required, they must be approved by the IACUC prior to implementation. o To know and apply institutional policies and standard operating procedures. o To perform only the procedures for which the animal user has been properly trained. o To treat the animals with care, respect and empathy.
Reporting Misuse, Mistreatment, or Non-Compliance
If misuse or mistreatment of animals is observed, it should be reported immediately to the IACUC
Chair, or any member of the IACUC. Allegations may be reported in person or anonymously. o All allegations will be handled by the IACUC according to the Protocol for handling allegations of protocol noncompliance or animal mistreatment . This policy contains provisions of a “whistleblower policy” protects the individual reporting misuse, mistreatment, or non-compliance. o The IACUC then makes recommendations to the "Institutional Official", who reviews the report and decides if additional action is needed. o If the IACUC decides that any animal activities need to be stopped to protect either animals or people, they are given clear regulatory authority to do so. In fact, if an IACUC votes to suspend a protocol or animal activity, that decision cannot be overturned by any administrator at the institution. o If an institution accepts PHS funds, any protocol suspension must be reported by the
Institutional Official to the Office of Laboratory Animal Welfare .
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THE ROLE OF THE IACUC
IACUC Basic Functions
The IACUC is responsible for making sure that all federal laws, regulations and policies are followed when investigators perform animal research. Some of responsibilities include:
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Reviewing and approvin g animal use protocols submitted by investigators.
Reviewing and approving all changes to ongoing animal use.
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Monitoring the animal care and use program by conducting thorough reviews of the program and inspections of the animal facilities semiannually and performing ongoing reviews of the program as the research is being conducted.
Appointment of IACUC members
Appointment of the IACUC members is made by the Institutional Official.
Timing of IACUC approval
Whether you are performing research or testing on animals, or using animals for teaching, you must receive IACUC approval before any use of animals begins . You must also receive approval for any changes (amendments) in procedures before implementing those changes.
PHS policy allows investigators to submit IACUC approval to the NIH for grant applications after peer review but prior to award of funding. This is termed “just-in-time” approval. Other funding agencies may require notification of approval by the IACUC before peer review.
The IACUC meets monthly to review and approve animal use protocols. If questions arise during the review process, there may be further delay of the approval of a protocol. It is the responsibility of the Principal Investigator to allow enough time for the approval process to meet grant application deadlines or to plan enough time for approval before the start of a project.
If the IACUC decides that any animal activities need to be stopped to protect either animals or people, they are given clear regulatory authority to do so. In fact, if an IACUC votes to suspend a protocol or animal activity, that decision cannot be overturned by any administrator at the institution.
DEVELOPMENT AND REVIEW OF A PROTOCOL FOR ANIMAL USE
The application for approved use of animals requires a great deal of information. This section describes some aspects of protocol development that must be considered when formulating an
IACUC protocol application.
Application forms
Forms and instructions may be obtained from the IACUC Staff Assistant.
Non-technical description
The protocol form requires a non-technical description of the project, justification of why animals are necessary for the study, justification of the number of animals requested, a complete description of procedures using animals and a statement describing the qualifications of personnel involved in the research.
Justification of the species, model and number of animals requested for the study
The investigator must consider scientific, ethical and humane issues in the selection of an animal model. The investigator must provide a justification for the selection of the species for the study.
It is also important to consider if the model: o Provides information that is accurate and relevant to the scientific questions being addressed
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Rev. 7/26/2005 General Training Course For Use Of Animals at Carolinas Medical Center o Can be accomplished in a humane fashion o Is available to the investigator at CMC o Has the characteristics such as size and stability to allow completion of the study
The study design must also minimize the possible repetition of previously published studies. The number of animals requested in the experimental groups must be justified either on the basis of previously obtained data or by the use of “effect size” calculation.
Consults required
By federal regulation, protocols that fall in categories C, D or E must be developed in consultation with the Clinical Veterinarian, the Attending Veterinarian or the Director of Comparative Medicine.
The Director of Comparative Medicine may also be consulted for assistance with protocol development.
Other Committee approvals
Protocols that involve infectious agents, carcinogens, radioisotopes, recombinant DNA or other hazardous or biohazardous agents require approval by the appropriate safety committee before
IACUC approval can be obtained.
Appropriate sedation, analgesia and anesthesia, and recognizing pain and distress
The IACUC protocol form must contain adequate details and description of the following: o Anesthetic administration dosing and schedule o Signs and symptoms for supplemental anesthetic o Post-surgical care and monitoring o Signs and symptoms of pain and suffering o Criteria for humane intervention and euthanization in case of complications
Justification for multiple major operative procedures
In addition to justifying surgical procedures, special scientific justification is required for performing more than one major survival procedure on a research animal.
Methods of euthanasia
Euthanasia is the act of killing an animal by methods that cause unconsciousness and death without pain or distress. The method of euthanasia must be described in the IACUC protocol.
Approved methods must be consistent with the 2000 Report of the American Veterinary Medical
Association (AVMA) Panel on Euthanasia.
Alternatives searches
The IACUC at CMC requires that an independent literature search be conducted by the
Reference Librarian at the AHEC library. This search will examine the literature to identify: o Systems for replacement of animals with inanimate, tissue culture or lower species o Opportunities for refinement of technique o Designs to reduce the number of groups or sample sizes of animals o The appropriateness of procedures in the chosen species o Publications on similar topics to evaluate possible duplicate studies
This search takes time to obtain. The Principal Investigator is encouraged to begin this literature search as soon as a reasonable draft of the protocol is devised. Protocols can not be reviewed by the IACUC without an accompanying literature search that has been conducted by the
AHEC Reference Librarian including a thoughtful review of the search in the protocol form.
Adequacy of training and experience of personnel in the proper handling of animals
One component of a successful research project is the proper handling and care of research animals. Federal regulations require that all individuals performing animal research be properly trained to perform their tasks. This reduces the possibility of stress and distress in the animal subjects, thereby reducing stress responses that might alter the outcome of the experiments.
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Proper handling techniques also reduce the chances of accidental injury to the animals or the researchers during the experiments.
Therefore, the IACUC requires certification that all animal researchers complete this training module and species specific training modules before beginning any activity under an approved
IACUC protocol.
Purchasing Animals
Purchase of animals for research must be made through the Department of Comparative
Medicine. This allows the coordination of animal ordering, evaluation of newly arrived animals for signs of disease, and availability of housing arrangements for the animals.
OCCUPATIONAL HEALTH AND SAFETY
The level and extent of personal participation in the occupational health and safety program for animal workers at CMC is based upon risk assessment. Accordingly, all individuals with access to the animal facilities at CMC must complete an initial "Health Questionnaire for the Laboratory
Animal Care Program" followed by an "Annual Medical Surveillance Update" form for on-going annual health monitoring. These forms must be returned to the Employee Health Department at
CMC for evaluation before individuals will gain and continue to have on-going access to the animal facilities. Additional follow up review may be required for those deemed by the Employee
Health Department to be at a high level of risk for occupational health and safety concerns.
Those identified will also complete a monthly monitoring "Occupational Health Program Z-1" form.
The following text provides a general overview of some occupational health issues that may be encountered in animal research
Zoonoses are natural hazards of biological origin in which the causative agents can be transmitted between animals and humans. Although infrequent, the risk of infection between animals and humans does exist.
Biohazards are infectious agents transmissible to and capable of inducing disease in humans.
Areas where biohazardous agents are in use must be labeled and specific recommendations and restrictions should be posted and enforced. Projects using biohazardous pathogens must undergo additional review by the Institutional Biosafety Committee or the Cannon Reseach
Center Safety Committee .
Standard Safe Work Practices and Procedures include the following steps: o Follow requirements for entry and exit from posted areas at all times. o Use good personal hygiene:
 Wash hands after animal contact and before leaving the laboratory or animal facility.
 Do not eat, drink, smoke, handle contact lenses, or apply cosmetics in work areas. o Receive adequate training in animal restraint and handling, chemical lab safety, and animal work-related hazards and safe work practices. o Wear personal protective equipment (PPE) as recommended. o Decontaminate equipment and work surfaces at least daily, and always after any spill of viable material. o Dispose of waste appropriately by following recommended guidelines. o Contaminated sharps should always be disposed of in a Biohazard Sharps Container. o Report promptly any accidents, illnesses and zoonotic diseases on the Report of
Occupational Illness and Injury (ROII) form. Visitors must fill out an Incident Report. o Notify your supervisor about the following events:
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 you become aware of a sick or dead animal
 you have a fever, diarrhea, or other symptoms that could be associated with the zoonotic diseases, biohazards or other hazardous materials that you work with.
Allergies
While anyone may develop allergies to animals, individuals with preexisting allergic conditions face a greater risk. Typical allergens include animal urine, saliva, dander, and hair. Most commonly, allergy presents with nasal symptoms, itchy eyes, and skin rashes. If ignored reactions can lead to more severe presentations, including asthma (cough, wheezing, and shortness of breath) and may persist beyond the period of animal exposure. In extreme cases, life-threatening anaphylactic reactions can occur.
Allergen exposure and the risk of development of occupational allergies and asthma can be reduced or eliminated by the following: o Use of cages with filter tops to reduce the load of environmental allergens. o Use of engineering controls such as biosafety cabinets, cage changeout hoods, and downdraft cage dumping stations. o Personal protective equipment (e.g. masks, gloves) and personal hygiene are important barriers in the exposure to animal allergens. Note that surgical disposable masks may not be effective against allergens. Properly fitted N95 respirators will provide superior protection.
Special recommendations for those with compromised health
Individuals with some health problems may be at an increased risk if exposed to infectious agents. Some examples of these conditions include immunosuppression, chronic liver or kidney disease, and heart problems, among others. Those with compromised health should notify the
Occupational Health Department or their personal care physician that they work with animals.
Physicians should be encouraged to consult with personnel of the Occupational Medicine
Department about the specific risks if additional information is needed.
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__________________________________ ________________
Print Name Date
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Signature
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Department
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Score
What two agencies are given authority by Congress to regulate the use of animals in teaching and research?
A. USDA & PHS (OLAW)
B. FBI & local police
C. IACUC Chairs Association & Smokey from “Smokey and the Bandit”
D. A & B
What animals are NOT included in the official USDA regulations definition of animals?
A. Rats of the genus Rattus
B. Dead dogs
C. Hamsters
What does AAALAC do?
A. Prints and updates the Guide for the Care and Use of Laboratory Animals
B. Accredits animal facilities who voluntarily submit to site visits every three years
C. Regulates animal research
D. All of the above
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Rev. 7/26/2005 General Training Course For Use Of Animals at Carolinas Medical Center
What are the three R’s to be considered when developing a project?
A. Review, replacement and refinement
B. Refinement, reduction and replacement
C. Replacement, review and reward
It is o.k. to implement a change in an animal procedure at the same time as you submit an amendment request to the IACUC. (True or False)
There is a “whistle blower policy” that protects an individual reporting misuse, mistreatment, or non-compliance. (True or False)
Which activities are the responsibilities of the IACUC?
A. Reviewing and approving animal use protocols
B. Reviewing and approving all changes to ongoing animal use
C. Monitoring the animal care and use program semiannually
D. All of the above
E. None of the above
“Just-in-time approval” means you can submit an amendment request right up to the time when you plan to implement a change in research. (True or False)
The IACUC has the regulatory authority to suspend or stop a protocol or animal activity. (True or
False)
The IACUC is comprised of members who are appointed by the:
A. Departmental Chairs
B. Attending Veterinarian
C. Institutional Official
When is it necessary to acquire approval from the Safety Committee or the Biosafety Committee before IACUC approval can be obtained?
A. When protocols involve the use of deceased animals
B. When protocols involve the use of carcinogens, infectious agents or radioisotopes
C. When protocols involve the use of recombinant DNA
D. All of the above
E. B & C
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What does the literature search do for the Principal Investigator?
A. Identifies opportunities for refinement of technique
B. Helps identify designs to reduce the number of groups or sample size of animals
C. Helps find systems for replacement of animals with inanimate, tissue culture or lower species
D. Identifies publications on similar topics to evaluate possible duplicative studies
E. Helps document the appropriateness of procedures in the chosen species
F. A, C & D only
G. All of the above
Multiple survival surgeries on a single animal may be approved by the IACUC under which condition?
A. If no more than 2 separate procedures are performed
B. Only under special circumstances where the surgeries are scientifically justified
C. Where the cost of the animals and/or the procedure dictates economy
Proper handling of animals in research and teaching is important because:
A. It reduces stress in the animal
B. It allows for safe administration of drugs
C. It minimizes the likelihood of injury to the handler
D. It is required by the Animal Welfare Regulations
E. All of the above
A CMC researcher with an approved IACUC protocol and a requisition form is authorized to directly purchase animals for those approved studies. (True or False)
D efine the term “zoonosis”.
All researchers with access to the animal facilities must be enrolled in the CMC Animal Use
Occupational Health program. (True or False)
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