Research Animal Facilites

Biomedical Research

Goal is to improve our knowledge of anatomy, physiology, disease processes and methods to control and treat disease

3 types of research

• Basic

• Applied

• Clinical

Applied Research

• Uses existing knowledge to solve a specific biomedical problem

  • Development of new vaccines or surgical procedures

• Performed on computer or mathematical models, cell or tissue cultures, or live animals

  • When live animals are selected as applied-research subjects, they are referred to as animal models

  • Choice of model is based on the ability of the model to mimic or predict response in another species

Clinical Research

• Builds on the knowledge gained in basic and applied research

• Always conducted on live animals, including humans

• Required by the FDA

• The FDA also requires that all research (basic, applied, and clinical) funded or reviewed by their agency be conducted in accordance with GLPs

Basic Research

• Advances fundamental knowledge of physical, chemical, and functional mechanisms of life processes and diseases

• Often performed using computer models or plants

• Provides guidance for applied or clinical research

Gnotobiology

• The study of animals with completely known flora and fauna

• Developed in 1950s

• Minimizes variations among individuals of the same species

Gnotobiology includes

• Axenic

• Gnotobiotic

• Specific pathogen free

• Cesrean derived

• Barrier sustained

Axenic

• "Without strangers"

• Germ free

• No evidence of microorganisms except those that pass to the animal through the placenta before birth

• Maintained in strict barrier facilities

• Food and water must be sterilized

  • Heavy supplementation of vitamins and minerals

• Grow faster, absorb fats faster, and live longer

Gnotobiotic

well defined flora

Specific Pathogen free

demonstrated to be free of certain pathogens but not all pathogens

Cesarean derived

• Delivered surgically by removal of the uterus

• Fetuses delivered in sterile isolation chamber

Barrier sustained

Cesarean delivered and maintained in a sterile, controlled environment

Convential

Undefined/unknown microflora

Research Design

• It is guided by initial question to be answered/problem solved

• Literature search is conducted to identify if question have already been addressed

  • No answers/solutions, hypothesis developed

• Research team develops experimental design

Developing an experimental design

• Methods, SOPs, biomedical model, personnel, budget

  • If using animal model, design must be approved by IACUC

• Identify variable (1 characteristic, condition, or factor) to study or apply treatment

• Assign test groups

  • Experimental group(s): variable is manipulated

  • Control group: no manipulation of variable

  • Random assignment: may e categorized by gender, age, etc

Research Team includes

• Principle Investigator

• Laboratory animal veterinarian

• Laboratory animal facility administrator

• Laboratory Animal Technicians/Technologist

Principle Investigator

• Develops hypothesis, major contribution experimental design

• Usually has advanced degree in specific field

• Complies, interprets data and reports findings

Laboratory animal veterinarian

• Member of ASLAP or ACLAM

• Oversees all aspects of animal health

• Ensures compliance with regulations related to animal care and use

ASLAP

American Society of Laboratory Animal Practitioners

ACLAM

American College of Laboratory Animal Medicine

Laboratory animal facility administrator

• Oversees all aspects of facility operation

  • Supervision of staff, record keeping

Laboratory Animal Technicians/Technologist

AALAS offers the certification exam for laboratory animal technicians, assistants, and technologist

• ALAT

• LAT

• LATG

• CMAR

ALAT

• Assistant laboratory animal technician

  • Entry-level certification

  • Oversees the daily care, feeding, comfort, and observation of research animals

LAT

• Laboratory animal technician

  • Requires a minimum of a GED or high school diploma and at least 3 years of experience

  • May perform procedures such as collecting blood samples, taking radiographs, assisting in surgery, and other advanced animal nursing procedures

  • Collect and process data

LATG

• Laboratory animal technologist

  • Requires a bachelor's degree and additional experience

  • May perform procedures such as collecting blood samples, taking radiographs, assisting in surgery, and other advanced animal nursing procedures

  • Collect and process data

CMAR

Certified Manager of Animal Resources

Why become AALAS certified?

• Is useful for promotions and hiring decisions

• Gives recognition as an industry professional

• Builds confidence and improves performance

• Evaluates strengths and weaknesses

• Enhances career satisfaction

Value of a RVT Education in a research environment

• Utilize education to support veterinary and research staff

  • Collect and process laboratory samples

  • Anesthesia support

  • Surgical support

  • Regulatory compliance

  • Husbandry management

  • Environmental enrichment

  • Clinical care for ill animals

  • Ensure humane animal care and valid research results

Technician involvment in Facility administration

• Record keeping

  • Animal welfare act/USDA

  • The Guide for the Care and Use of Laboratory Animals

  • Public Health Services

• Cost calculations

  • Per diem - total cost per day for housing of animal

  • Includes: Feeding, watering, bedding, cleaning, waste disposal, vet care, costs related to operation of facility

• Inventory control

• Animal acquisition

RVT research careers

• Animal Health Technician

• Animal Care Staff Technician

• Training and Techniques Coordinator

• Environmental Enrichment Coordinator

• Animal Trainer

• Research Associate

• Supervisor/Manager

• IACUC Specialist/Administrator

Facility Design

• Quality of research data directly connected to quality of animal care

• Appropriate housing and care are essential

• Specific design needs vary with type of research

• Focus on minimizing spread of disease in the facility

• Constant and controlled environment

Standard areas

• Animal rooms

• Surgical suie

• Cage wash

• Receiving and Storage

• Laboratories

• Locker rooms with showers

• Personnel areas

Animal rooms

• Sufficient number for multiple species

• Consistent environmental controls

  • Variable could compromise research

• Easy to clean, waterproof walls, floors, and electrical sources, drains

Surgical Suite

• Areas for animal prep, surgery, and recovery

• Aseptic technique

• Special instrumentation and equipment

Cage Wash

• Separate area for washing cages and other supplies

• Away from animal rooms

• Clean vs. Dirty sides

• Ventilation and noise control

• Walk - through, cabinet, tunnel types

• High temps for sanitization

Receiveing and Storage

• Medications, food, supplies, and equipment

• Separated from animal rooms

• Feed and bedding storage

  • Free of vermin and moisture

  • Low temperature and humidity

  • At least 20 cm off the floor and away from the walls

Laboratories

• All procedures conducted outside of the animal rooms

• Include: Radiology, necropsy, treatment

Personnel Areas

• Break rooms

• Offices

• Changing and showers

Construction materials

Waterproof and seamless

Interfaces between walls, windows, doors, and floors

• Not damaged by regular use

  • Movement of large equipment

• Cleaned regularly

Windows and Doors

• Windows not usually present

• Doors designed to open inward

  • Can have windows in doors for observation

Types of Facilities

• Conventional

• Double Corridor

• Barrier

• Containment

Conventional Facility

• Animal and support rooms have single doors opening into a central corridor

• Common in small facilities

• Requires special attention to minimize disease spread

• Cages cleaned within room

  • Dirty cages taken to cage wash

  • Try to move dirty cages in one direction

Double Corridor facility

• Aka - Clean/dirty facility

• Rooms have two doors

  • One into clean corridor

  • One into dirty corridor

• One-way traffic

• Personnel cannot leave by the clean corridor door

Barrier facility

• Similar to double corridor except personnel must shower before entering animal rooms

• Must wear disposable clothing

• Entry areas have an airlock

  • UV light

• All materials must be autoclaved before entering

• Air pressure is carefully monitored

• Used for germ-free animals

Containment facility

• Similar to barrier

• Personnel usually required to shower before leaving facility

• All materials used in rooms must be autoclaved before disposal

• Houses animals with infectious or zoonotic diseases

• Air leaving facility is filtered or heated to remove infectious organisms

  • High efficiency particular air (HEPA) filters

Environmental concerns

• Maintain constant conditions

• Systems to monitor animals rooms

• Macroenvironments

• Microenviroments

Conditions we must maintain

• Temp

• Humidity

• Ventilation

• Air pressure

• Lighting

• Noise

• Social

Macroenvironment

• All components within the animal room

• Optimal level species specific

Microenvironment

• Factors within the primary enclosure of the animal

  • Cage, run, pen

• Affected by this

  • Ex. Bottom rack cages lower temp than those on top rack

Temperature

• Optimal levels species dependent

  • Rodents - higher temps than rabbits

• Temp maintained in the thermoneutral zone (TNZ)

  • Range of temp where an animal does not need physical or chemical mechanisms to control heat production or loss

Variation in temperature and humidity can affect what?

metabolism and behavior of animals, affect data

Humdity

• Optimal level species specific

• Most rooms maintained at 45-55%

  • Rodents 40%-70%; dogs, cat, primates 30-70%

Proper ventilation

• Supplies oxygen and removes odors and contaminants from the air

• Ammonia

• Animal rooms must have 10-15 air changes per hour

• Recirculated air must go through HEPA filters first

  • Not recommended to recirculate

How often should the air change in animal rooms

10-15 per hour

Ammonia

• By product of breakdown of animal waste

• Toxic levels if improper ventilation

Positive air pressure

• Air flows from room to the outside when door is opened

• Ex. Surgical suites

Negative air pressure

• Air flows from the outside into the room when the door is opened

• Ex. Quarantine, Infectious animals

Lighting

• Non natural light/windows in animals rooms

• Seasonal light changes = variable

• Diurnal illumination system

  • Lights on for 12 hours, off for 12 hours

• Breeding animals have special requirements, species specific

Diurnal illuminarion system

Lights on for 12 hours, off for 12 hours

Noise

• Many species sensitive

• Special alarms used in facilities

• House animals away from loud equipment

• PPE for personnel

Social Environment

• Physical contact, visual, auditory, and olfactory communication with members of the same species

• Understanding of species' normal behavior essential

  • Group house when possible

    • Dog, primates

  • Consider activity patterns

    • Play, foraging, resting boards/ledges above floor

Primary Enclosures

• The Outer limit within which the animal can move without human assistance

• Must be capable of containing without unnecessary restraint

• Protect from hazards and environmental extremes, provide for well-being

• Proper feeding and watering equipment

• Allow for observation without disturbing normal physiologic and behavioral functions

Caging Materials

• Stainless steel

• Aluminum

• Plastics

Stainless steel

• Strongest, rust free, resistant to most cleaning chemicals

• Expensive, low temperatures

Aluminum

Lightweight, inexpensive, less durable material

Plastics

• Polycarbonate

• Polypropylene

• Polystyrene

Polycarbonate

High impact strength, high heat/chemical resistance, transparent, expensive

Polypropylene

Moderate impact strength, heat/chemical resistance, opaque

Polystyrene

Low impact strength least heat/chemical resistance, disposable cages

Types of Caging

Species Specific, experimental design

• Shoebox

• Suspended

• Metabolism cages

• Gang gases

• Transport cages

• Pens or runs

• Activity cage

• Inhalation cage

• recovery cage

Shoebox cage

• Plastic with solid bottom

• Top with a grid of stainless steel

  • May incorporate a feeding station and

• Rodents

Suspended

• Plastic or stainless steel with mesh bottom or plastic grid floor

• Slide in and out of rack on rails

• Excellent ventilation

• Poor microenvironment

Metabolism Cages

• Used to collect feces and urine

• Food and water outside of the cage

Gang cages

• Group housing

• Configuration depends on species

• Multiple food and water sites

Transport cages

• Wheels move animals from one location to another

• May have a squeeze area

• No food or water - short periods of use unless transported long distance

Pens or runs

• Large pens for dogs, livestock

• May be outdoors or indoors

  • Special considerations for outdoor areas

Activity cage

• Exercise

• Species specific

Inhalation cages

Enclosed chamber with strict environmental parameters

Recovery Cage

• Strict control of temperature, humidity, oxygen

• May have IV lines, access ports, and monitoring

Space requirement

• Calculations require a large number of factors

  • Large enough for normal postural movements and enrichment

  • Calculated on animal weight and body surface area

    • Space requirements can be found in the Guide

  • Based on animal health, reproduction, growth, behavior, and activity

  • Group housed vs. Single housed

Environmental enrichment

• has significant impact on animals health

• Goal is to provide a mechanism for animal to express an innate behavior with positive effects on its health and well-being

• Research data may be compromised if appropriate EE is not provided

Considering normal behavior for species for environmental enrichment

• Some species need vertical space

• Resting ledges

• Boxes for burrowing

• Chew toys

• Climbing ropes

• Hidden treats

• Running wheels

Exercise Programs

• Animal Welfare Act

  • Requires dogs to have appropriate exercise

  • If singly housed and with less than twice the required floor space - must have exercise program

  • Group housed - no need for exercise program if floor space is adequate

  • Dogs that cannot have direct physical contact with other dogs must be provided regular human interaction

Feed

• Readily available

• Not allowed to be contaminated with feces or urine

• Stainless steel or plastic

• Special considerations for group or outdoor housing

• V-shaped for many rodents

• J-shaped for rabbits and guinea pigs

• Stainless steel or crock bowls for dogs, cats, and primates

Water

• Fresh water all the time

• Water bottle

  • Shoebox-fit into V-shaped trough

  • Suspended within cage

    • Glass

  • Outside of cage

    • Plastic - polycarbonate

  • Ball bearing

    • Water moves with animal contact

• Automatic watering systems

  • Expensive, car/maintenance

  • Built in pressure - reducing stations

  • Filtering systems

Federal law mandates for Animal Acquistion

• Animal be acquired from USDA-Licensed dealers

• Dealers must:

  • Adhere to the AWA standards of care

  • Comply with detailed record-keeping and waiting period requirements

  • Undergo unannounced USDA inspections

Animal Acquisition includes

• Purpose bred

• Random source

• Quarantine

• Acclimation period may be required post quarantine

Purpose bred

• Bred specifically for research purposes

• Class A

• Almost half of the dogs and cats used in research are purpose bred

Random Source

• Class B dealers are permitted to obtain animals from shelters and other sources

• Some research protocols prohibit the use of random source animals

• Some state and local laws prohibit dealers from obtaining shelter animals for research

Quarantine

• All animals must be quarantined prior to induction into the colon

• Allows animals to recover from the stress of transportation

• Prevents diseases

• Minimum 48 hours

• Physical exam, fecal, and blood tests

Quality assurance

• Monitoring of the health of the animals

• Periodic physical examinations and laboratory testing

• Sentinel Animals

Sentinel Animals

• Susceptible to particular pathogens

• Located in various animal rooms and areas

• Periodically tested

  • Serologic

  • Fecal

  • Blood cultures

Facility security

• Welfare of the animals and personnel and protection of reliable research

• Controlled access to facility and individual rooms

  • Keyed entry

  • Coded keyless entry

  • Changed regularly

• Integrated security and emergency systems

OSHA

• Enforces laws to protect workers

• Hazards must be identified and employees must be trained

  • Allergens, noise, zoonoses, waste handling, chemical safety, microbiological, anesthetic, and radiation hazards

• "Right to Know"

  • Informed about potential exposure to chemical hazards

  • List of hazardous chemicals

  • PPE provided

  • SDS/Secondary container labeling

  • Safety

• CDC and NIH/PHS require OSHA program

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

  • Biosafety in Microbiological and Biomedical laboratories

Biosafety Hazard Considerations

• Biologic substances containing infectious agents that pose a threat to human health

  • Used needles, patient samples

• CDC guidelines for safe handling and management

• Containers with specific symbol

• Biosafety Levels

  • I, II, III, IV

  • Great the number, greater the risk

Level I biosafety hazard

• Agents that ordinarily do not cause harm to healthy humans

  • Soaps

  • Animal vaccines

  • Species-specific diseases

• Normal sanitation protocols

Level II biosafety hazard

• Agents have potential to cause human disease if handled incorrectly

  • Toxoplasmosis, Salmonellosis

• Limited access

•  PPE

• Sharps containers

• Instructions for disposal or decontamination

Level III biosafety hazard

• Agents that can cause serious potentially lethal disease

  • Mycobacterium tuberculosis

• Controlled access

• Decontamination of waste, cages, clothing, and equipment

• Testing of personnel

• Use of biosafety cabinets during procedures

• PPE

Level IV biosafety hazard

• Agents pose a high risk of causing life-threatening diseases

  • Ebola

• Strict protocols

• Advanced training