LAT Unit 1 (chap 1-4)
how long do grants provide money for usually?
3 to 5 years
What is AAALAC
Association for Assessment and Accreditation of Laboratory Animal Care. - private, nonprofit organization that promotes the humane treatment of animals in science through voluntary accreditation and assessment of animal care programs. Accreditation is attained through a peer-review process.
___________ provides grants for ____________
NSF, nonbiomedical scientific research
How often do these unannounced APHIS inspections occur?
annually
How does a PAM program do its job?
by observing procedures being performed, reviewing animal health records, inspecting animal areas, and observing animals on study, they evaluate their findings in accordance with approved protocols, internal policies, and applicable regulations and guidelines. they then report these findings with the research staff and the IACUC
Steps of the Scientific Method
define questions, formulate objective framework, hypothesis, create research design, identify variables, data collection and analyze, report data and conclusion
Whose responsible for monitoring compliance with NIH policy of 1971?
delegated to the Office for protection from research risks (OPRR) which later became the office of lab animal welfare (OLAW)
___________ is the last source of funding for ____________ and ___________. The use of these funds _______________________________________________________
donations, universities, foundations, may or may not be restricted
Animal Welfare Act (1970)
enforcement delegated to USDA amended from lab animal welfare act (1966) covers all warm blooded animals, including animals sold as pets or used in exhibits. requires all dealers to be licensed and mandates use of pain relieving drugs for animals used in teaching, research, and testing. also establishes care and use standards for research animals including housing, sale, transportation, research facility registration, and the ID of dogs and cats.
whistle blower policy
most institutions have this. it protects anyone reporting animal welfare concerns from any discrimination or reprisal. both the guide and animal welfare regulations require such a policy. and the guide states that personnel should be able to convey such concerns anonymously.
What does a good occupational health and safety program do?
takes into account training and experience levels among employees, the possibility of exposure across the different areas of the facility, and the types of research and animal species, including the presence of pathogens, radioisotopes, and toxic chemicals
category C pain
teaching, research, experiments, or tests that cause no pain or distress and thus do not require the use of pain relieving drugs
IACUC records that must be kept on file
meeting minutes, proposed animal use protocols and significant changes to those protocols, semiannual reports, and any recommendations
two publications that could assist a facility in preparation of a APHIS inspection?
Animal care inspection guide (USDA created, gives institutions a better understanding of the inspection process) and the Animal Care Policy Manual (created by APHIS, provides guidance in the interpretation of specifications contained in the AWR, such as those pertaining to expired medical materials, surgery, pre and post procedural care, health records, and euthanasia.
US Endangered Species Act of 1973
was passed to implement CITES. The responsibility for implementing and enforcing this law was delegated to the United states Fish and Wildlife services (FWS) division of management authority.
Controlled Substances Act
specify the administrative requirements for the procurement, storage, use, and disposal of controlled substances
Category E pain
teaching, experiments, research, surgery, or tests causing pain or distress to the animals for which appropriate anesthetic, analgesic, or tranquilizing drugs were not used because they would have adversely affected the procedures, results, or interpretation.
what is the only regulatory requirement pertaining to animal ID?
that dogs and cats have a collar, tag, or tattoo. and all ID tags must be kept for a year after the animal is euthanized or disposed of for possible review by USDA inspector
the use of controlled substances is regulated by
the US drug enforcement agency (DEA)
What does the guide say about ethics in regards to lab animals & scientific research?
"Humane care means those actions taken to assure that lab animals are treated according to high ethical and scientific standards. Implementing a humane care and respect for animals is valued and encouraged, underlies the core requirements of the guide and the laws and regulations it supports"
What do VMOs do during APHIS inspections?
- VMO tours facility assesses animal use program by reviewing relevant documentations such as protocols, training records, and IACUC meeting minutes
what info must be given to a grant agency by the PI
- a detailed description of the research goals -the scientific basis of the study, a thorough review of relevant literature, and preliminary data and results -all procedures to be performed
AVMA Guidelines on Euthanasia categorize different methods as
- acceptable - acceptable with conditions (such as weight range for animals or use of special equipment) - unacceptable
facility records required for animal research facilities:
- animal receipt, tracking, and disposition records (especially for USDA covered animals) -quarantine and testing records -animal husbandry logs - animal census records - environmental enrichment logs - records of proper sanitation and housekeeping for the entire facility -records of environmental conditions within the facility -vet care and surgical records -drug and supply inventories -controlled substance records -records of drug or test article receipt, storage, and use -equipment inventory, receipt, and maintenance records -supply receipt, storage, rotation, and use records -employee training records, both initial and ongoing -occupational health and safety records -IACUC review records
areas where SOPs and documentation are required
- animal room construction: composition of floors, walls, ceilings, doors; lighting intensity; emergency plans, including back-up generators; monitoring of frequency of repairs performed on the room. -enviromental conditions: reliability of controls for the heating, ventilation, and air conditioning system (HVAC); documentation of temperature and humidity, including deviations and calibrations; air exchange rates - animal rooms and caging: documentation for each bedding and cage change, feed and water changes, cage maintenance, and room sanitization. - Common areas and storage: cleaning and maintenance of hallways, animal and material receiving areas; procedure rooms; food storage rotation and temperature; vermin control in food and bedding storage areas. - Cage wash areas: scheduled and unscheduled machine maintenance, verification of appropriate cage wash and autoclave temperatures; detergent concentrations used; construction materials; safety precautions, including proper personal protective equipment and safe working practices.
Parts of the AWR
- definition of terms - regulations - standards - rules of practice
key factors in containment
- facility design - perform comprehensive risk assessment to assign a BSL level - staff are trained to strictly adhere to standards - personnel are consistent in use of correct PPE
types of raw data in an animal facility
- facility logs -laboratory work sheets, notes -equipment or instrument outputs (such as chart strips) - computer printouts -biological speicmens
GLP SOP requirements
- if any activity is considered routine then there needs to be an SOP for it - process must be described in detail, including who is responsible for performing the task, the frequency, and step by step instructions. -documentation is required for each step, the person performing the tasks must initial and date the form - if a step is not documented then it was not performed and this deviation from the SOP will have to be explained on the final report of the study
what must a facility have in order to meet GLP requirements?
- must have sufficient number of animal rooms to ensure spaces separation -isolation of individual projects -isolation of quarantine areas - must have separate storage areas for feed, bedding, supplies, and equipment away from animal areas -environmental conditions must be regulated -wastes must be collected and handled to minimize vermin infestation, odors, and contamination -equipment must be of appropriate design and capacity to conduct the study, inspected, cleaned, and maintained -written records of all testing, calibration, and inspections must be kept
PHS policy describes multiple components of a successful animal care and use plan such as:
- the location, construction, components, management, and operation of the facility where animals will be housed - the physical and social environment of the animals - animal husbandry, including food, water, bedding, sanitation, waste disposal, and pest control -animal identification, genetic monitoring, and animal health records -daily observations of and care for animals, including weekends and holidays
What are some of the US Govt. principle's core values regarding the ethical treatment of lab animals
- the use of animals in research should be scientifically relevant and appropirate - animals used in research should be maintained in a way that provides them with as much physical and psychological wellbeing as possible - animals used in research should not be subjected to unnecessary pain and distress. if these effects are unavoidable, efforts should be made to minimize the extent and duration of the pain and distress - if severe pain in animals cannot be relieved, they should be humanely euthanized in order to end their suffering
What do these IACUC review say and who are they submitted to?
. Once the semiannual program review and facility inspections have been completed, the IACUC is responsible for generating a report of these evaluations and submitting the report to the IO. The report lists all departures from the relevant regulations, policies, and guidelines, and the plan for correcting these departures. Deficiencies are categorized as minor or significant deficiencies. A significant deficiency is one that, in the judgment of the IACUC, poses a threat to the health or safety of the animals.
process for making ethical decisions regarding animal treatment
1. identify the issue 2. gather and assess all facts involved 3. identify the individuals and groups affected by the issue, and the impact the issue has on each 4. identify values that play a role in the decision 5. identify and evaluate possible solutions 6. decide on course of action
IACUC inspections occur every
6 months
CITES Appendix 1
Animals close to extinction. nearly all trade of these animals is illegal (pandas)
Class A dealers
Breed their own animals
1971 NIH policy
Care and Treatment of Laboratory Animals- introduced self regulation by way of an animal care committee to ensure the humane care and use of laboratory animals. required NIH funded research using warm blood animals to provide assurance that maintenance and treatment would be performed in accordance with AWA and the guide.
how do corporations fund their research?
Commercial profit from sales of their products
AWA Covered Species
Dog, Cat, Non-human primate, Guinea Pig, Hamster, Rabbit, other warm blooded animals kept as pets or used or intended for use in research, tests, experiments, or exhibits
BSL-2
Indigenous microorganisms that can lead to diseases of varying severity in healthy adults.
BSL-3
Indigenous or exotic microorganisms that cause serious or potentially lethal disease through respiratory transmission
IACUC
Institutional Animal Care and Use Committee: charged with reviewing animal research procedures and ensuring that all regulations are adhered to
BSL-1
Microorganisms not known to cause disease in healthy adults.
________________ & _________________ require an IACUC review every _______ months while the guide says reviews are performed every _____
OLAW, USDA, 6 months, year
US government Principles for the utilization and care of vertebrate animals used in testing, research, and training are applied to research funded by _________
PHS
biological risk assessment
Principal investigators, laboratory directors, and facility directors determine the best methods for protecting workers against exposure to potentially infectious agents and materials by performing a biological risk assessment. The Institutional Biosafety Committee (IBC), IACUC, biological safety professionals, and laboratory animal veterinarians also participate in this assessment.
what replaced the NIH policy, Care and Treatment of Lab Animals (1971)?
Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS policy) 1973
who is notified if a suspension of a protocol or study is called for by the IACUC?
Suspension of animal activities requires the notification of USDA, OLAW, and AAALAC.
what must a facility do the be accredited with AAALAC?
The institution submits a program description, which is a highly detailed document containing information related to the institution's; animal care and use policies and responsibilities; animal environment, housing, and management; veterinary medical care; and physical plant. Representatives of the AAALAC Council on Accreditation conduct an on-site review of the institution's animal care and use program. Institutions in the United States are evaluated based on their adherence to federal, state, and local laws; regulations; and the standards outlined in the Guide and the Ag Guide. Additional mandates may apply in other countries. The team reports their findings to the Council on Accreditation, which is responsible for making all final accreditation decisions.
animal welfare regulations enforced by ____________ requires that an IACUC have 3 members ___________, ___________, _____________
USDA, chairperson, a vet, a member not associated with the institution
Post approval monitoring
a program devised to ensure that IACUC approved procedures are being followed, although this process is not federally mandated the AWR and PHS policy do require the IACUC to continually review ongoing animal studies.
category B pain
animals being bred, conditioned, of held for use in teaching, testing, experiments, research, or surgery, but not yet used for such purposes
Quality assurance unit
can be a department, an employee, or a contractor but must not participate in the study and cannot be the study director. QAU audits all GLP compliant studies to ensure compliance with the GLPS with regards to personnel, procedures, SOPS, documentation, facilities, equipment, reports, and archives.
CITES appendix II
contains species that are likely to become endangered
other granting agencies
department of defense department of energy USDA NASA army, navy, air force uniformed services university of the health sciences (USUHS) the defense advanced research projects agency (DARPA) armed forces radiobiology research institue (AFRRI) VA
Animal welfare regulations (AWR)
describes what a facility must do to comply with the AWA, authorized by the AWA and published in the federal register. In part 2 (regulations) AWR requires instituitons to: - registration of research institutions and licensing of dealers - oversight by an IACUC that meets the AWA guidelines - a research staff qualified for humane animal care and use - an adequate veterinary care program - proper ID of animals - adequate record keeping and reporting procedures - adherence to mandated animal holding periods and facility conditions -compliance with the regulations regarding procurement of random source dogs and cats
what must be submitted annually in order to keep accreditation with AAALAC? and how often do inspections occur?
institutions must submit an annual report describing changes in the animal care and use program. AAALAC performs site visits of accredited institutions every 3 years.
Records to keep for USDA and length of time they must be kept
minutes of IACUC meetings --- 3 years protocol records ---------------3 years semi-annual inspection records-- 3 years dog/cat acquistion and disposal records--3 years official USDA dog and cat tags ----1 year
records to keep for PHS (NIH) and length of time to keep
minutes of IACUC meetings --- 3 years semi-annual inpsection reports--3 years accrediation inspection reports--3 years protocol records-----------------3 years after completion of study
Occupational Health and Safety in the Care and Use of Research Animals (Occ Health)
published by the Institute of Laboratory Animal Research, gives guidance on creating and implementing an institutional occupational health and safety program and addresses hazard control in the laboratory animal facility, including animal allergy, zoonosis, and physical and chemical injury.
What must a nonfederal research institution do if using animals covered by AWA? how often? who is in charge of making sure the facility is in compliance with AWA?
register with USDA, registration must be updated every 3 years by submitting a new registration form, and the IO is responsible for compliance with AWA
Microenvironment
the individual cage of animals
Macroenvironment
the room in which an animal is housed
must
used to describe aspects of an animal care program that are considered essential or imperative to the proper humane care and use of lab animals
should
used to describe aspects of an animal care program that are strong recommendations for achieving a goal
In what instance does the guide have regulatory authority?
with institutions conducting PHS supported activities in animal research programs
Main public granting agency in US
NIH and NSF
what is an example of the implications of a suspension?
NIH does not allow grant funds to be used for activities that were not approved by the IACUC. Therefore, if researchers were not following their approved IACUC protocol, the institution may have to return grant money to NIH for the period of time that the institution was not in compliance.
__________ & ______________ require enriching the _____________ of some species & planning protocols with attention to issues of ______________ &______________.
NIH guidelines, federal regulations, environment, pain, pain relief
__________ a branch of ___________ is the primary funding agency for ____________ ________________
NIH, Public health service (PHS), biomedical research
PHS policy enforced by _________ requires at least 5 members ___________, _________, __________, _________, __________
OLAW (office of lab animal welfare), chairperson, a vet, a practicing scientist, a non scientist, a community member
differences between PHS and AWA regulatory requirements
PHS- 5 IACUC members, includes all vertebrate animals, inspections are for cause, requires and animal welfare assurance, and is enforced by OLAW AWA- 3 IACUC members, includes warm-blooded vertebrate animals, excluding birds, rats, and mice bred for research, inspections occur annually and are unannounced, must be a registered institution, and is enforced by USDA, APHIS
depending on funding source and species used institutions must follow
- AWA and AWR -PHS policy, The guide -the ag guide -relevant institutional policies
determining the most appropriate method of euthanasia depends on what factors?
- animal species and age - available means of restraint - skill of personnel - personnel safety and risk - the number of animals to be euthanized
GLP requirements involving animal care:
- any new animal must be quarantined and their health status evaluated prior to use -animals must be identified accurately -all housing areas must be kept clean and sanitized regularly -the containment levels of feed and water should be analyzed periodically and documented - test articles and control articles must be labeled with identity, storage conditions, concentration, expiration, and origin
archives
-All protocols, raw data, specimens, documentation, and final reports must be archived during or at the close of a GLP study. Even if a study is incomplete or restarted, all the data must be archived. -Specimens must be kept for as long as reanalysis would yield sound information. A study protocol should specify the time the raw data (including wet specimens) will be retained or archived at the end of a study and where the data will be stored. -Some archives are maintained for as long as the sponsor holds a marketing or research permit for the test substance. Often, archives are kept past the permit duration because the data may be needed for protection against liability. -Archives are kept for 5 years after study completion if they support a research or marketing permit that was not approved. -Archives are kept for 2 years after study completion if the study is not submitted for a marketing permit or is discontinued
IACUC approval is granted for?
1 to 3 years per AWR 1 year for USDA covered species
what other documents does the guide take into consideration?
AWA, AWR, PHS policy, and the US government priciples for the utilization and care of vertebrate animals used in testing, research, and training
Animal welfare assurance
Before the PHS may award a grant or contract that involves the use of animals, the recipient institution must file an approved Animal Welfare Assurance, signed by the institutional official (IO), with OLAW. The Animal Welfare Assurance commits the institution to compliance with the PHS Policy, the AVMA Guidelines for the Euthanasia of Animals2, the Guide, and the AWA.
what does the PHS policy require?
IACUC review of all protocols, an animal program review every 6 months, and the use of the guide for all animal use programs receiving federal research funding
flow of IACUC reports
IACUC submits report to IO -> IO sumits it to applicable oversight agencies (OLAW and USDA) -> IACUC establishes a mechanism to review all concerns regarding animal care and use brought to its attention -> the committee continually reviews protocols and is authorized to suspend any activities that do not comply with applicable policies, regulations, and guidelines.
Biosafety in Microbiological and Biomedical Laboratories
In 1974, the Classification of Etiologic Agents on the Basis of the Hazard was published by the US Department of Health, Education and Welfare, Public Health Service. This reference, later renamed Biosafety in Microbiological and Biomedical Laboratories (BMBL), describes a set of guidelines established by the CDC and the NIH for the safe handling and containment of biological agents in a laboratory setting, including infectious microorganisms and potentially hazardous biological materials.
Class B dealers
Purchase and may condition random-source animals for resale
GLP study separation requirements:
Testing facilities are required to have an adequate set-up for the number of animal rooms or areas to ensure proper separation of species or test systems, isolation of individual projects, isolation of newly received animals from outside sources until their health status is evaluated, and separation of routine and specialized housing of animals. A common misconception is that studies must be kept in separate rooms. The requirement states that studies must be separated in such a way that no mix-up can be made among study materials, including test systems.
test system
a comprehensive term for the animal or any other entity that is administered a substance in a GLP study. EPA GLP's state that a test system can be a physical or chemical medium such as soil or water. GLP's set a performance standard for housing and care of test systems and animal welfare is not specified by the GLP regulations but it is assumed
Federal Food, Drug, and Cosmetic Act of 1938
established oversight for the safety of food, drugs, and cosmetics. The responsibility for implementing and enforcing this law was delegated to the FDA. Documentation must be stored in a way that allows it to be readily available on demand. GLP studies also require much more documentation than projects conducted in a non-GLP environment.
what is required by AWA for dogs and NHP?
exercise programs for dogs and psychological enrichment for NHP
The US government principles
added to PHS policy in 1996, they are: - the transportation, care and the use of animals should be in accordance with the AWA and other applicable federal laws, guidelines, and policies - procedures involving animals should be designed and performed with due consideration to their relevance to human or animal health, the advancement of knowledge, or the good of society - the animals selected for a procedure should be an appropriate species and quality and the minimum number required to obtain valid results. methods such as mathematical models, computer simulation, and in vitro biological systems should be considered - Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals. - Procedures with animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents. - Animals that would otherwise suffer severe or chronic pain or distress that cannot be relieved should be painlessly killed at the end of the procedure or, if appropriate, during the procedure. - The living conditions of animals should be appropriate for their species and contribute to their health and comfort. Normally, the housing, feeding, and care of all animals used for biomedical purposes must be directed by a veterinarian or other scientist trained and experienced in the proper care, handling, and use of the species being maintained or studied. In any case, veterinary care shall be provided as indicated. - Investigators and other personnel shall be appropriately qualified and experienced for conducting procedures on living animals. Adequate arrangements shall be made for their in-service training, including the proper and humane care and use of laboratory animals. - Where exceptions are required in relation to the provisions of these Principles, the decisions should not rest with the investigators directly concerned but should be made, with due regard to Principle II, by an appropriate review group such as an institutional animal care and use committee. Such exceptions should not be made solely for the purposes of teaching or demonstration.
records to keep for FDA (GLP)
all records of the study are to be maintained for 5 years following submission of the application for FDA approval or 2 years after approval whichever is shorter
AWA excluded species
birds, rats of the genus Rattus, mice of the genus mus bred for use in research, horses not used for research purposes, farm animals such as livestock or poultry used or intended to be used as food, fiber, improving food/fiber quality, animal nutrition, breeding, management, or production efficiency
CITES appendix III
contains species that are protected by a member country that requests the cooperation of the other member countries to prevent exploitation
Category D pain
experiments, teaching, research, experiments, or tests causing pain or distress to the animals for which appropriate anesthetic, analgesic, or tranquilizing drugs were used
Convention on International Trade in Endangered Species of Wild Fauna or Flora (CITES)
implemented to prevent the endangerment or extinction of species due to international trade. it is an agreement between countries which provides a framework for the member countries to create legislation within the individual countries. requires a licensing system in order to import or export covered species. member countries must also designate a management authority for administering licenses and a scientific authority that provides advice on effects of trade on the species status
Guide for the care and use of laboratory animals (the Guide)
made in 1963 by the Animal Care Panel and supported by NIH. important source of information for researchers, animal care and use program management, vets, and IACUC. Makes recommendations regarding the humane care and use of lab animals based on performance standards meaning it measures success on the outcome of programs and procedures rather than the means of achieving the outcome.
GLP regulations
mandated by the FDA and the EPA. set standards for safety testing on types of commercial products such as cosmetics, pharmaceuticals, vet drugs, food additives, vaccines, biological, agricultural pesticides, toxic chemicals, and livestock nutrition supplements. FDA and EPA conduct unannounced for cause inspections and they assess the facility, equipment, specimens, data, documentation, and reports.
BSL-4
most lethal microorganisms sealed, negative pressure; "hot zone" -exhaust air is filtered twice through HEPA filters
Animal and Plant Health Inspection Service (APHIS)
of the USDA is tasked with administering the AWA and AWR. VMO (veterinary medical officers) are responsible for conducting unannounced inspections of registered facilities to assure they are following AWA and AWR
3 R's
replacement- can animals be replaced by a nonanimal alternative or lower sentient species without interfering with the objectives of the study reduction- can fewer animals be used without altering the validity of the study refinement- can the procedures used in the study be refined to lessen pain and distress or minimize the number of potentially painful procedures that the animals must undergo during the study
program reviews and inspections by the IACUC are done by:
reviewing and updating the AAALAC program description, reviewing the program in the context of the four major sections of the Guide, or using the OLAW semiannual program and facility review checklist. The program review also includes the inspection of all of the institution's animal facilities, including animal study areas and satellites. Typically, an inspection involves a subcommittee of IACUC members passing through each room where animals are housed or taken with procedures
