LAT Chapter 1 & 2

Types of euthanasia modes of action

Hypoxia (CO2 inhalation), direct depression of neurons necessary for life (anesthetic overdose), physical disruption of brain activity (electrocution); methods of euthanasia are categorized by species and are deemed either acceptable or unacceptable for that species

IACUC suspension authority

In serious deficiencies, IACUC may suspend any animal-related activity, including an entire protocol. IACUC and the IO determine the appropriate action to be taken; suspension of animal activities require notification of USDA, OLAW and AAALAC. May have to return their grant money to NIH

OLAW responsibilities

monitor compliance with PHS Policy; expects institutions to self-regulate and report deviances from PHS Policy and Animal Welfare Assurance; inspects a handful of institutions randomly each year and conducts for-cause inspections

Archives

All protocols, raw data, specimens, documentation and final reports must be archived during or at the close of a GLP study; specimens must be kept for as long as reanalysis would yield sound information; biological fluids must be stored frozen; archives kept for 5 years after study completion if they support a research or marketing permit that was not approved, kept for 2 years after study completion if the study is not submitted for a marketing permit or is discontinued

Animal environment, housing and management

Physical environment includes the microenvironment and the macroenvironment, housing, temperature, humidity, ventilation, air quality, illumination, noise and vibration control. Housing considerations include caging, environmental enrichment, space and special considerations such as sheltered or outdoor housing and naturalistic environments

OLAW

was originally the Office for Protection from Research Risks (OPRR)

Ideal euthanasia agent

would rapidly induce loss of consciousness so death would follow quickly and present no hazards for personnel administering it.. however no drug exists

Language in The Guide

"must" is used to describe animal care program aspects that are essential or imperative to proper humane care and use of lab animals; "should" describes strong recommendations for achieving a goal

The research process

1. Define the question 2. Formulate an objective framework 3. Establish a hypothesis 4. Create a research design 5. Identify Variables 6. Collect and analyze data 7. Report data and conclusions

Euthanasia

A method of killing that minimizes pain, distress and anxiety experienced by the animal prior to loss of consciousness, and causes rapid loss of consciousness followed by cardiac or respiratory arrest and death.

Oversight of institutional research programs is done by...

Animal Welfare Act and Regulations, Public Health Service Policy, the Guide for the Care and Use of Laboratory Animals (the Guide), the Guide for the Care and Use of Agricultural Animals in research and teaching, and relevant institutional policies.

Animal Facility Definition according to PHS

Any building, room, area, enclosure or vehicle used for animal confinement, transport, maintenance, breeding or experiments in which animals are housed for more than 24 hours (as compared to 12 hours in the AWR)

Institutional Officer Responsibilities

As designated by the Guide, the IO bears ultimate responsibility for the animal care and use program; he or she has authority to allocate resources to the program and should provide leadership to program personnel

USDA Pain categories

Category B: animals being bred, conditioned or held for use in teaching, testing, experiments, etc but not yet used for those purposes Category C: Use but no pain or distress, so do not require pain-relieving drugs (example is vaccinations) Category D: Causing pain or distress to the animals but appropriate anesthetic, analgesic or tranquilizing drugs are used (ex. is surgery) Category E: Causing pain or distress but anesthetics, analgesics or tranquilizing drugs are not used because they would have adversely affected the procedures, results, or interpretations (inducing a disease)

Test system

Comprehensive term under GLPs referring to the animals or any other entity that is administered a substance in a GLP study. Test systems can also be a physical or chemical medium like soil or water

1979 revision of PHS

Definition of animal changed to include all vertebrates

AWR

Describes what a facility must do to comply with the AWA

Postapproval monitoring

Ensures that IACUC-approved procedures are being followed; the formal process is not required by federal mandate but AWR and PHS Policy do require the IACUC to continually review ongoing animal studies

Funding administration

For most institutions, there is usually an Office of Research and Grants led by a dean or vice president of research.

Institutional Animal Care and Use Committee

Has oversight responsibilities for the institution's research program and receives support from the administrative unit.

AWA Recordkeeping Requirements

IACUC records that must be kept on file include meeting minutes, proposed animal use protocols and significant changes to those protocols, semiannual reports, and any recommendations. USDA requires records for live dogs and cats and any offspring born of these animals at the research facility, as well as records of disposition for species covered by the USDA

Research facility requirements

If using animal species covered by AWA, must establish an IACUC, employ an attending veterinarian under formal arrangements, training for all personnel involved in animal care, treatment and use

Animal Welfare Assurance

In order to receive grant or contract involving the use of animals, recipient institution must file an approved Animal Welfare Assurance to commit the institution to compliance with the PHS Policy, AVMA Guidelines on Euthanasia, the Guide and the AWA; signed by the IO with OLAW

Protocol approval by IACUC

In planning a research study involving animals, scientists must submit an animal use protocol to the IACUC for review which must be approved in order for the PI to begin a study using animals

Annual report to USDA

Institutions using USDA-covered species must submit an annual report to USDA to demonstrate that it's following the AWA, its animal care meets professionally accepted standards, the PIs consider alternatives to painful procedures listed in the animal use protocols and that any exceptions to the regulations are approved by the institution's IACUC; must also state the location of all the institution's animal facilities and how many animals were used in the previous year under each USDA Pain Category

When was the AWA made and who enforces it?

Laboratory Animal Welfare Act of 1966 was amended in 1970 and changed to the AWA; the USDA implements and enforces this law

Class B animal dealers

Licensed by USDA to purchase and resell animals including random-source dogs or cats, import nonhuman primates and resell animals from research facilities

Protocol approval

May be approved for 1-3 years depending upon species used and institutional policies; protocols for USDA covered species may only be approved for 1 year

Identification of animals

Must be properly identified at acquisition, transportation, sale or disposal; any dog, cat or nonhuman primate transported to a research facility must be accompanied by a health certificate issued by a licensed veterinarian; USDA may provide exceptions to the health certificate requirement for animals with a health condition necessary for the approved protocol

Confirming death after euthanasia

Necessary before disposal of animal; a combination of criteria is most reliable to confirm death including lack of pulse, breathing, corneal reflex and response to firm toe pinch, inability to hear respiratory sounds and heart beat by use of stethoscope, graying of mucous membranes and rigor mortis. NONE of these signs alone, except rigor mortis confirms death

Regulations for interstate sale and transportation of animals

Rabies vaccination requirements for dogs and cats; health certificates provided for dogs, cats and nonhuman primates; transporting sick or infected animals or those exposed to any transmissible disease from another state or area is prohibited

IACUC review of animal care and use program

Required to monitor programs every 6 months through review of the program and routine inspections of the animal facilities; most highly visible responsibility or an IACUC

IACUC and the community

Serves as an information resource on animal welfare and a liaison on animal research concerns to the institution and the community

Good Laboratory Practices

Set of controls for research labs to ensure the consistency of procedures and reliability of data; FDA and EPA mandate these standards for safety testing on the types of commercial products each agency regulates; may conduct inspections of animal facilities and unannounced for-cause inspections. Some animal facilities operate exclusively under GLP regulations, while many others only conduct GLP studies from time to time

NSF (National Science Foundation)

Supports research in scientific areas that are primarily nonbiomedical in nature but which may involve animals such as in basic biology and behavior, mathematics, physics, chemistry, climatology, nanotechnology, engineering and astronomy

The Guide influences

Takes into consideration the AWA, AWR, PHS Policy, and the US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research and Training

APHIS

The Animal and Plant Health Inspection Service of the USDA administers both the AWA and AWR

The Guide, PHS and AAALAC

The Guide has regulatory authority for institutions conducting PHS supported activities in animal research programs; AAALAC endorses the Guide as one of its standards for accreditation of lab animal programs

Inspection of facilities under AWA

USDA Veterinary Medical Officers or VMOs conduct unannounced inspections at least annually of registered institutions within their respective regions; use the USDA Animal Care Inspection Guide for inspection process while the APHIS' Animal Care Policy Manual provides guidance in the interpretation of specifications in the AWR

Grant application

prepared and submitted by the Principal Investigator; provides a detailed description of the research goals, the scientific basis of the study, a thorough review of relevant literature, any preliminary data and results, and all procedures to be performed.

Guide for the Care and Use of Agricultural Animals in Research and Teaching

provides guidelines for programs that use agricultural animals for agricultural research or teaching; specific standards provided for beef and dairy cattle, horses, poultry, sheep, goats and swine; both USDA and AAALAC use the Ag Guide when inspecting agricultural animals used in biomedical research

IACUC tasks

review the protocols of research projects to ensure compliance with all relevant federal, state and local laws, regulations and institutional policies on animal welfare

AWA (enforced by USDA) IACUC requirements:

Must have at least 3 members: a chairperson, a veterinarian with training or experience in laboratory animal science and medicine, and a member of the community (nonaffiliated)

PHS Policy IACUC requirements

Must have at least 5 members: chairperson, veterinarian, practicing scientist w/ animal research experience, nonscientist, community member; HOWEVER, the nonscientist and community member can be the same person

Factors for methods of euthanasia

Must take into account species, age, available means of restraint, skill of personnel, personnel safety risks and the number of animals to be euthanized; also may include animal health and age, institutional policies, and equipment available within the facility

PHS Policy

NIH Policy in 1971 was replaced by PHS Policy on Humane Care and Use of Laboratory Animals in 1973; required institutions using warm-blooded animals in research funded by NIH to provide an assurance that the maintenance and treatment of animals would be in accordance with the AWA and the Guide; Office of Laboratory Animal Welfare monitors compliance with PHS

Registration under AWA

Nonfederal research facilities must register with the USDA if using species covered by the AWA; registration must be updated every 3 years by submitting a new registration form that is signed by the IO, who ensures the organization is in compliance with the AWA

Facility inspections and program review

PHS policy and AWR require that IACUC conduct semiannual inspections of the animal facilities; the Guide states that inspections and program review should be performed at least annually; inspection findings are reported to the IO of the research facility, which are added to the institutional records and must be available during outside inspections; IACUC also conducts semiannual review of the research program's policies and procedures

Differences between AWA and PHS policy

-AWA requires 3 IACUC members while PHS requires 5 -AWA does not cover mice or rats bred for research, birds, farm animals, or horses not used for research, whereas PHS covers all vertebrates -Under AWA, the USDA and APHIS conduct annual, unannounced facility inspections; Under PHS, OLAW conducts random inspections of some institutions and for cause inspections -Under AWA, research facilities must register with USDA and re-register every 3 years; under PHS, research facilities must file and sign an Animal Welfare Assurance -the AWA is enforced by USDA and APHIS, and the PHS is enforced by OLAW

NIH (National Institute of Health)

A branch of the Public Health Service that is the primary granting agency that supports biomedical research; most of their grants go to research programs at colleges, universities, and some private corporations and federal agencies

Research definition

A systematic investigation to establish facts that employs reliable methods of collecting valid data to find answers to specific scientific questions

Importation regulations

Animals must be shipped from the country of origin, the necessary export documents and proper identification are provided, that animals appear healthy, and that they enter the United States through designated ports of entry; disease-causing agents and animal vectors are admissible only by special permit

AAALAC Facility Accreditation

Association for Assessment and Accreditation of Laboratory Animal Care International is a private, nonprofit organization that promotes the humane treatment of animals in science through voluntary accreditation and assessment of animal care programs; accredited institutions are respected within the field of biomedical research; evaluations based upon adherence to federal, state, local laws, regulations and standards outlined in the Guide and the Ag Guide; visits accredited institutions every 3 years

Private funding sources

Biotechnology and pharmaceutical companies are examples of private businesses that do research to create a product they can sell; like prescription drugs, orthopedic devices and diagnostic equipment; scientists in private companies do not apply for grants but do have to compete for funding

Which animals are excluded from the AWA?

Birds, rats of the genus Rattus, mice from the genus Mus, horses not being used for research purposes, farm animals

The Guide

Developed by the Animal Care Panel in 1963 and supported by the NIH; revised most recently in 2011. Provides information for researchers, animal care and use program management, laboratory animal veterinarians, and IACUCs.

Raw data

GLP standards specify how raw data should be handled, including collection, analysis, interpretation and archiving. Includes observations, measurements and specimens; includes facility logs, lab work sheets, notes, equipment or instrument output, computer prinouts, and biological specimens

Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES)

Implemented by the US Endangered Species Act to prevent the endangerment or extinction of species due to international trade; contains appendices I, II and III to list species that are protected at various levels: Appendix I contains most endangered, Appendix II contains species likely to become endangered, Appendix III contains species protected by a member country that requests the cooperation of other member countries

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

Incorporated into the PHS Policy in 1996 (the Guide also endorses these principles) -Transportation, care and use of animals should be in accordance with AWA and other applicable federal laws -Procedures should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge or the good of society -Animals selected should be of an appropriate species, quality and minimum number required to obtain valid results -Avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices is imperative; assume that procedures that cause pain in humans also cause pain in animals; use appropriate sedation, analgesia, or anesthetics -animals that would otherwise suffer severe or chronic pain that cannot be relieved should be euthanized

Class A animal dealers

Licensed by USDA to raise and sell animals themselves (purpose bred animals)

IACUC mandates

Mandated by federal law and must adhere to guidelines, federal regulations and policies, and institutional policies that govern the use of animals in research; the IACUC's function are specified by both the PHS and USDA; The institutional official (IO) appoints the members to the IACUC and is ultimately responsible for the entire animal care and use program

Occupational Health and Safety in the Care and Use of Research Animals

Provides guidance on creating and implementing an institutional occupational health and safety program and addresses hazard control in the laboratory animal facility; should take into account the training and experience levels among employees, the possibility of exposure across the different areas of the facility, the types of research and animal species, including the presence of pathogens, radioisotopes and toxic chemicals; varies greatly among institutions

IACUC responsibilities according to the Guide

Reviews and approves proposed animal use protocols and amendments, monitoring animal use for compliance after work has begun, reviewing the entire care and use program and inspecting the facilities where animals are used. PROTOCOL REVIEW REQUIRES special attention to experimental and humane endpoints, unexpected outcomes, physical restraint procedures, multiple survival surgical procedures, food and fluid regulation, the use of medications and other substances, field investigations and agricultural animals

Standard operating procedures

SOPs are detailed documents that describe all procedures to be performed and are easily accessible to employees; crucial for conducting, monitoring and documenting all procedures related to the housing, feeding and care of the animals; Required by GLP regulations

AVMA Guidelines on Euthanasia

Separate euthanasia methods by mode of action, provide guidelines for situations with special consideration; USDA, OLAW and AAALAC require that animal facilities adhere to these guidelines

Biosafety in Microbiological and Biomedical Laboratories

Set of guidelines established by the CDC and NIH for the safe handling and containment of biological agents in a laboratory setting, including infectious microorganisms and potentially hazardous biological materials; promotes biosafety, which promotes the reduction or elimination of the exposure of laboratory workers other persons and the outside environment to potentially hazardous agents; sets Biosafety Level 1 through Biosafety Level 4

Attending Veterinarian responsibilities

The Guide states that the attending veterinarian is responsible for the health and wellbeing of the animals in the program and should have access to all animals and resources available to manage the program effectively

IACUC duties under PHS

conduct the annual review of the institution's animal facilities and to review proposed animal activities; review all protocols and an animal program review every 6 months, and the use of The Guide for all animal use programs receiving federal research funds