Good Animal Facility Management and Husbandry. Chou C. Hong, DVM.,PhD.,DACVM Member, Council on Accreditation AAALAC International

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Good Animal Facility Management and Husbandry Chou C. Hong, DVM.,PhD.,DACVM Member, Council on Accreditation AAALAC International 1

Good Animal Facility Management and Husbandry 2

The Animal Care and Use Program 3

The Guide Performance Standards: Provides scientifically, technically, and humanely appropriate guides for animal care and use OLAW standard AAALAC standard 4

A good animal facility A good management program provides the environment, housing and care that permit animals to grow, mature, reproduce and maintain good health; provides for their well-being; and minimizes variations that can affect research results -the Guide 5

Institutional policies OHSP IACUC Adequate Veterinary Care Administrative Organization 6

Animal management Animal Space Provisions Support Service Sanitation Practices Caging/Housing System Aseptic surgery Husbandry Practices Identification/Record Keeping Vermin Control 7

Veterinary care Preventive Medicine Disease Diagnosis, Control, Treatment Surgical & Postsurgical Care Anesthesia/Analgesia Euthanasia 8

Physical plant HVAC Survival Surgery Support Facility Maintenance Personnel Safety Concerns General Storage Conditions Sanitation of Facilities 9

Physical plant (cont.) Illumination Emergency Power Physical Plant Design Security 10

IACUC Responsibilities and Function 11

12

Composition of the IACUC USDA requires: At least 3 members Veterinarian, Non-affiliated member COA (Taiwan): At least 3 members Veterinarian, Non-affiliated member PHS Policy requires: At least 5 members Veterinarian, Nonscientist, Community/Nonaffiliated member, at least 1 practicing scientist 13

IACUC functions Semi-annual review of the Animal Care & Use Program Veterinary care Personnel qualification Adequate animal facilities and husbandry Program of occupational health and safety Investigate concerns involving the care and use of animals, e.g., animal welfare, complain, etc 14

IACUC responsibility: Review of scientific merit Protocols involving animals should have a sound research design, the animals selected should yield valid results, and the project should have relevance and scientific value (i.e. merit). (based on PHS Policy and USDA Regulations) 15

PHS policy on scientific merit Procedures with animals will avoid or minimize discomfort, distress, and pain to the animals, consistent with sound research design. - PHS Policy (IVC1a) The animals selected for a procedure should be of an appropriate species and quality and the minimum number required to obtain valid results. -U.S. Government Principles III 16

The USDA on scientific merit Rationale for species Appropriate species to obtain valid results Activities do not unnecessarily duplicate Procedures for the conduct of scientifically valuable research - 9 CFR 2.31 17

Protocol review Replacement/Reduction: Project Overview Use of Live Animals Literature Searches for Alternatives Experimental Design Justification of Animal Numbers Refinement: Procedural Description Pain, Distress and Discomfort Analgesia Euthanasia Training & Experience 18

Special review issues Multiple Survival Surgery Prolonged Restraint Food and Water Restriction Use of paralytic agents Pain/distress Category E procedures 19

Pain and Distress 20

Pain and distress Pain in laboratory animals is a major animal welfare issue that must be addressed We need to consider: When pain might occur, how long it might last Pain management (Anesthesia and Analgesia) Pain assessment Pain occurs in animals; that it can result in suffering, in a similar way to pain in man The avoidance and alleviation of Pain should be given a high priority. 21

Why treat pain? Legal and ethical reason Beneficial for the animal Beneficial for research Rapid return to normal function A higher survival rate Counteract physiological changes Thoracic and abdominal pain affect ventilation Reduction in food and water consumption 22

Recognition of pain Prey animals mask pain Nocturnal species Signs to look for General appearance and condition Attitude, posture and movements Interactions with cage mates Reactions to manipulation Food and water consumption Production of faeces and urine Species-typical signs of pain and distress Procedure-specific signs 23

Pain relief: Use of analgesics 1. NSAIDs Salicylates (aspirin) Ketoprofen: (Romefen ) 2. Opioids Intraoperative pain relief (Hypnorm ) Postoperative pain relief (Buprenorphine :Temgesic ) 3. NMDA-receptor antagonists 4. Alpha-2-agonists (Xylaxine: Rompun ) 5. Sedatives and tranquillizers Diazepam, acepromazine, fluanisone 24

USDA Pain/Distress Categories B = animals used only for breeding purposes (breeder moms, stud males, culled pups, etc.) C = momentary (or less) pain or distress Needle stick for blood draw or administration of euthanasia No anesthesia needed for a similar procedure in a human 25

USDA Pain/Distress Categories D = Some pain/distress, treated with anesthetic, analgesic or tranquilizing drugs Similar procedure in a human would require topical or systemic anesthesia Post-surgical pain treated with analgesia Anesthesia used for restraint Cardiac Perfusion? Maybe not.. 26

USDA Pain/Distress Categories E = Pain/distress for which the use of appropriate anesthetic, analgesic or tranquilizing drugs would adversely affect the research. Analgesic studies Death as an endpoint REQUIRES SCIENTIFIC JUSTIFICATION 27

28

Euthanasia The bringing about of a gentle and easy death. Humane killing with the minimum of pain, fear and distress. AVMA Guidelines for the Euthanasia of Animal: 2013 Edition 29

Why carry out euthanasia? End of experiment Continuing adverse effects Pain, distress or suffering exceeding stated level If state of health or welfare give cause for concern Unwanted stock For blood or other tissues 30

Humane method of killing "The killing of an animal with a minimum of physical and mental suffering, depending on the species." Requirements: Minimise fear and distress. Separate area away from other animals. Ensure operator competence. Reliable method. 31

Method Painless and stress free. State of unconsciousness should be reached rapidly and maintained until death. Easy to administer. Safe for staff who perform it. Appropriate for species, bodyweight, and stage of development. Compatible with experimental objectives. 32

Choice of method Chemical methods: Inhalant agents: CO 2 asphyxia Non-inhalant agents: overdose of anaesthetic Physical methods: Concussion Decapitation Cervical dislocation. 33

Methods used for small animals Methods Rodent less than 125 g Rodent/Rabbit 125 g~ 1 kg Rodent/Rabbit <2 kg CO2 asphyxiation Barbiturate overdose, IV (100 mg/kg) Barbiturate overdose, IP (100 mg/kg) Exsanguination (under anesthesia) Decapitation (under anesthesia) Cervical dislocation (under anesthesia) Decapitation (no anesthesia) Cervical dislocation (no anesthesia) :Recommended; :not permitted; :not recommended, can be applied after IACUC approval 34

Confirmation of death Absence of pulse / heartbeat. Decapitation. Destruction of brain. Severing of major blood vessels to terminate flow of blood to brain. Onset of rigor mortis (return to individual cage for c.30 mins). 35

Zoonosis and OSHA Regulation 36

Occupational Health and Safety Regulations 37

Occupational health and safety program Risk Assessment and hazard identification Medical surveillance Training Personnel hygiene PPE Facilities Procedures and monitoring 38

Program design 1. Knowing the hazard 2. Avoiding and controlling exposures 3. Training and education 4. Rules and guidelines 5. Consistency 6. Record keeping and monitoring 7. Commitment and coordination 39

Program management 1. Animal care and use 2. Research 3. Environmental health and safety 4. Occupational health 5. Administration and management 6. IACUC provide links among the five above institutional functions. 40

Potential hazards for laboratory animal employee 1. Allergens 2. Biological hazards--zoonotic diseases 3. Physical and chemical hazards 4. Protocol related hazards 41

Allergens in the animal facility 42

Prevention of allergy 1. Ventilated hood, biosafety cabinet 2. Animal rooms ventilation (>10 ACH) 3. Wear protective clothing 4. Wash hands frequently 5. Keep cages and your work area clean 43

Zoonoses disease Diseases and infections which are naturally transmitted between vertebrate animals and humans - WHO 1959 44

Does NOT include Fish and reptile toxins Zoonoses Allergies to vertebrates Diseases in which animal-derived food serves as a vehicle (e.g. hepatitis A contaminated deli meat) Experimentally transmitted diseases 45

Zoonoses: Importance Economics Zoonotic disease are expensive Rabies post-exposure prophylaxis GI illness due to Salmonella or Campylobacter lost productivity, medical costs Import/Export BSE restriction on cattle Avian Influenza restriction on avian species Travel/Globalization Remote area accessibility 46

Zoonotic diseases of rodents and rabbits Zoonosis Agent Species Route of transmission Rat bite fever Streptobacillus moniliformis, Spirillum minus Rodents Bites, Fecal-oral (S moniliformis) Bites (S. minus) Leptospirosis Leptospira spp. Rodent/Rabbit Aerosol, direct contact with urine, water or soil Lymphocytic Choriomeningitis LCM virus Rodents Aerosol, bites, direct contact, fecal-oral. Korean Hemorrhagic Fever Hanta viruses Rodents Aerosol, direct contact, fecal-oral. Cheyletiellosis Cheyletiella parasitivorax Rabbit Direct contact Dermatophytosis (Ringworm) Trichophyton sp. Microsporum sp. Rodent/Rabbit Direct contact Tapeworm Hymenolepis nana Rodents Fecal-oral Pneumocystis Pneumocystis carinii Rodent/Rabbit Aerosol carinii infection 47

Control of zoonotic diseases in the animal facility 1. Engineering control (facility design) 2. Animal quarantine and stabilization 3. Work practices and procedures 4. Personal protective equipment 5. Training and education 6. Role of the facility director and IACUC 7. Institutional policies and rules 48

Physical related hazards 1. Animal bites, scratches, and related hazards 2. Sharp objects: needles, broken glass etc., 3. Flammable materials 4. Pressure vessels 5. Lighting and Electricity 6. Radiation and Lasers 8. Noise 9. Machinery 49

Chemical related hazards 1. Disinfectants, Pesticides, detergents 2. Anesthetic gas and chemicals 3. Chemical for preserving tissues, formaldehyde 4. Pharmaceutics Material Safety Data Sheet (MSDS) 50

Protocol related hazards 1. Involving chemicals of unknown hazards 2. Involving chemicals: carcinogens, mutagens and potential hazards 3. Involving infectious agents: BSL 1, 2, 3, and 4 4. Procedures and manipulation 51

What are the hallmarks of a good OHSP? Strong administrative support Sound implementation strategies Effective coordination of components 52

Conclusion 53

Conclusion Virtually every medical achievement of the last century has depended directly or indirectly on research in animals ~ US Public Health Service

Conclusion Good Animal Care & Use program in research is possible Good Animal Care & Use program in research is necessary Good Animal Care & Use program in research supports research outcomes Good Animal Care & Use program in research is the right thing to do! 55

Thank You for Your Attention 56