introduction to the use of animals in biomedical research research animal facility veterinary and...

INTRODUCTION TO THE USE OF ANIMALS

IN BIOMEDICAL RESEARCH

Research Animal Facility Veterinary and IACUC Staff

DBL/EBR 02/11/04

OUTLINE

Why learn about animals in research?Regulatory requirementsThe IACUCThe 3 Rs and alternativesBiohazards and zoonoses: Maintaining human

healthSecurity and RAF accessAnimal health and animal procedures

REGULATORY REQUIREMENTS

Animal Welfare Act (AWA)

Public Health Service Research Extension Act (PHSREA)

AAALAC International

Animal Welfare Act (AWA)

First enacted by Congress in 1966Was the first law in United States

pertaining to use of animals in research

Animal Welfare Act (AWA)

Enforced by the USDAUnannounced Site Visits by a USDA

Veterinarian (VMO)Amended in 1970, 1976 and 1985

PHS and AAALAC cover all vertebrate animals including

cold blooded vertebrates.

The Public Health Service Health Research Extension Act, 1985

Covers all vertebrate animals Establishes Institutional Animal Care & Use Committee

(IACUC)

Enforced by the Office for Laboratory Animal Welfare (OLAW)

Must be observed by all institutions receiving NIH funds

Basic guidelines for Humane Animal Care and Use are mandated

AAALAC International Association for the Assessment and Accreditation of Laboratory Animal Care

Voluntary membershipPeer reviews and site visitsProfessional evaluations with stringent

standardsUses the Guide for the Care and Use of

Laboratory Animals, “The Guide”UMDNJ, Newark has maintained full

AAALAC accreditation since 1981

Institutional Animal Care & Use Committee

Became mandatory in 1985• Mandated by the Animal Welfare Act• Public Health Service and • AAALAC International

Institutional Animal Care & Use Committee Regulations and guidelines

• Members of IACUC (PHS

requirement)

• Scientist• Veterinarian• Chair• Nonaffiliated member• Nonscientist

Institutional Animal Care & Use Committee Membership

IACUC committee: currently 15 members• Chair (Dr. Fitzgerald-Bocarsly)• Attending Veterinarian (Dr. Ryden)• Staff Veterinarian • Non-affiliated member• Nonscientist member • Scientists – Many departments represented

Institutional Animal Care & Use Committee Responsibilities

• Review and approve proposed activities• Inspect areas where animals are housed and

used

• Review the RAF program for the humane care and use of animals

• Review and investigate concerns regarding the care and use of animals

Institutional Animal Care & Use Committee Protocols

• Before any proposed research or teaching activity can be undertaken at any institution, an IACUC application must be approved by Committee.

• This application is called the IACUC Protocol.

• At the VA is called ACORP (Animal Component of Research Protocol)

Institutional Animal Care & Use Committee Protocol annual reviews

• Protocols are approved for 3 years with annual reviews.

• Annual review notices are sent 2 months before the expiration date--required for continued protocol approval during the three-year period.

• An expired protocol inhibits an investigator from ordering animals or performing any experiments

Institutional Animal Care & Use Committee AMENDMENTS

An amendment must be submitted if significant changes are planned after a protocol has been approved by the Committee.• Change in Procedures• Change in Species• Change in Anesthesia• Addition of Animals• Change in Endpoint

Personnel Add/Delete Form

An Add/Delete Form must be submitted if New personnel are added or if

Personnel are deleted

Requirement for Training

New personnel are required to 1) Attend RAF Orientation and2) To documents their experience and

training using the species and performing the procedures to be used or

3) To state who will train them

Institutional Animal Care & Use Committee Protocol questions

• Experimental Endpoint• Humane Endpoint• Animal must be humanely euthanized if in

distress which cannot be treated• Euthanasia• USDA category• Literature search for alternatives• Biohazard Approval if relevant

Humane Endpoint vs Experimental Endpoint

• Experimental Endpoint• Planned endpoint when animal will be

euthanized and tissues harvested for in vitro analysis

• Humane Endpoint• Unplanned endpoint (earlier than Experimental

endpoint) if something goes wrong

• Animal must be humanely euthanized if in distress which cannot be treated

Institutional Animal Care & Use Committee Alternatives

• Search for alternatives• The 3 R’s

o Replacemento Refinemento Reduction

Russell and Burch (1959)

Institutional Animal Care & Use Committee Replacement

• Replacing animals with in vitro modelso cell cultureso tissue cultureso computer models

• Replacing a higher more sentient animal with a lower less sentient animalo Instead of a monkey use a rat

Institutional Animal Care & Use Committee Refinement

• Use of less invasive procedures• Ex: Laparoscopy instead of laparotomy• Blood collection from vein instead of

cardiac puncture

Institutional Animal Care & Use Committee Reduction

• Reduction in number of animals used• Reduction in number of procedures

performed on one animal

Institutional Animal Care & Use Committee Considerations

• Anesthesia & Postoperative Care• Physical discomfort• Number of animals requested• Justification for using animals• RAF orientation and training

Institutional Animal Care & Use Committee Literature search

• Search to document previous studies• Search for alternatives• Mandated by the AWA• Documented in the IACUC protocol

Institutional Animal Care & Use Committee USDA category

• B Breeding colonies or animals not yet used in research

• C No or minimal pain and distress• D Pain or distress alleviated by

analgesics, anesthetics or tranquilizers• E Pain or distress NOT alleviated by

drugs

Institutional Animal Care & Use Committee Protocol review process

• IACUC meets the 1st Tuesday of each month.

• Veterinary and administrative Prereview

• Committee Review: Two reviewers

Institutional Animal Care & Use Committee Review process

Three possible outcomes at the meeting:• Approval

• Conditional Approval

• Tabled

Institutional Animal Care & Use Committee Biohazard review

Protocols using the following hazardous chemicals or biologicals are submitted to the Biohazard Committee for review:• Chemical Hazards• Carcinogens• Radiation Hazards• Infectious Hazards• Bloodborne pathogens• Recombinant DNA

Institutional Animal Care & Use Committee Animal Biosafety Committee (ABC)

The ABC meets monthly.It consists of the following members:

• A representative from EOHSS• Pharmacologist & Toxicologist• Microbiologist/Virologist• Attending Veterinarian• Facility Manager ICPH

Institutional Animal Care & Use Committee Institutional Biosafety Committee (IBC)

• A subsection of the IBC meets monthly • IBC is administered by EOHSS• Available on the UMDNJ web• Reviews Recombinant and infectious

studies

Institutional Animal Care & Use Committee Other Agencies

• OSHA Occupational Safety and Health Administration

• PEOSH Public Employees Occupational Safety and Health • EOHSS Environmental and Occupational Health and Safety

Services

NJ and UMDNJ state regulations

Institutional Animal Care & Use Committee How to report concerns about care and

use of laboratory animals

• Speak to any member of the IACUC or any of the Veterinarians (who are

members of the IACUC)• IACUC membership and contact

information is posted in the Animal Research Facility

Your concern will be kept confidential

Occupational Health

Pre-employment and Annual Physical Exams if personnel has significant contact with and exposure to animals

Tetanus immunizationTB test if working with nonhuman

primatesOther vaccinations as recommended and

indicated

Occupational Health Health concerns

What do you think is the most pervasive health concern are from working with research animals?

Allergies to animals

1) Allergies30 – 40 % of staff working full-time with animals may develop allergies over time(primarily to mice, rats, cats, rabbits)

2) Bites and scratches may occurBest prevention is to be trained in handling each species and to wear appropriate clothing

How to protect yourself

Wear designated clothing over or instead of your street clothes when working with your animals: Long-sleeved lab coat or scrubs

Wear gloves when working with rodentsWash your hands when you are finished

handling your animals

Clothing requirements for the RAF

Please note that lab coat or scrubs are mandatory before entering RAF animal rooms

All RAF rodent rooms require some level of Personnel Protective Equipment (PPE)

READ DOOR SIGNS BEFORE ENTERING ANY ANIMAL OR ANIMAL PROCEDURE ROOM

HAZARDS

SPECIES-SPECIFIC CONCERNS

Most rodents, rabbits: Minor concerns

Cats: Toxoplasmosis

Nonhuman Primates: Herpes-BShigellaTuberculosisOther zoonotic diseases

Bite and Scratch Prevention

Each animal room has a bite/scratch kitIf bitten or scratched, do the following:

Put animal down in cageScrub wound for 2 minutes by the clockReport incident to RAFReport incidence to your SupervisorIf indicated see doctor

Women of child-bearing ageLimit or avoid exposure to:

X-raysGas anesthesiaCat feces and litter box (Toxoplasmosis)LiftingBrDU (Bromodeoxyuridine)Other: as indicated by your doctorNotify your supervisor

Injuries: How to proceed

1. First aid Animal bite or scratch: Use Bite and Scratch kit Other: Fall, Cut

2. Incident report (Witness documented)3. Risk & Claims (UMDNJ employees)4. Own/Assigned doctor (students,

residents)4. Medical attention as needed5. Insurance as arranged by department

RAF Card key access

SA17= Front door by personnel elevators • PERSONNEL ENTRY

SA18= Back door by freight elevators• ANIMAL AND EQUIPMENT ENTRY

SA19= Barrier access. Restricted.• BARRIER MICE AND QUARANTINE AND BIOHAZARD

STUDIES

Checking and using access

Wait 3 days after RAF OrientationThen swipe your card key and see if it

worksIf not working within a week report back

to RAF

Visitors policy

No children allowed Research and student personnel must be 17

years or older Please make appointment if you want a tour PLEASE DO NOT TAKE VISITORS TO SEE YOUR

ANIMALS WITHOUT CLEARING THIS WITH RAF ADMINISTRATION (Mr. Rodriguez or Dr. Ryden)

Do not take pictures without clearing this with RAF Veterinary Staff

Let’s take a break

Sign up for RAF card key access

Room key if applicable

Animal Procedures and Veterinary Care

Three (3) Veterinarians Four (4) Sr. Veterinary Technicians

support animal care and researchTraining Coordinator

ANIMAL ORDERS

ORDER FORMS

• DEADLINE: Tuesdays @ 10:00

• COMMERCIAL vendors only

• Specify preferred housing room

• IACUC protocol must be active

ANIMAL ORDERS

DELIVERIES

• Pigs and rabbits: Mondays

• Canines: Tuesdays

• Rodents: Tues and Wed.

ANIMAL ORDERS

TRANSPORT IS STRESSFUL

ACCLIMATION • Rodents (3 days)• Large animals (7 days)

QUARANTINE• Rodents (0 or 8 weeks)• Most large animals (1

week)

ANIMAL ORDERS

TRANSPORT ON-CAMPUS

• Return animals to the same animal room on the same day; overnight housing in the lab requires special IACUC approval

• Submit completed Animal Transfer Form if a room change is proposed

• Cover animals with dark plastic bag—use new bag each time

• Transfer to clean rodent cages for post-operative recovery for return transport

ANIMAL ORDERS

TRANSPORT OFF-CAMPUS

• All animal shipments from UMDNJ must be approved by Research Animal FacilityComplete Animal Shipment Form.

• All Animal shipments from UMDNJ must be approved by Office of Patents and LicensingComplete Material Transfer Agreement

• All shipments to UMDNJ must be approved and coordinated by Research Animal Facility in advance of shipment.Complete Animal Shipment Form.

ANIMAL ORDERS

CAGE & CARCASS TRANSPORT

• CARCASS DISPOSAL in necropsy freezer in A-664 or in box outside of

A-664

• SOILED CAGE RETURN• Return to dirty cage wash inside of plastic bag• Please return all cages

ANIMAL ORDERS

vendor classes

Class A vendors• Purpose-bred animals for

research• Very stringent health

monitoring• Very stringent genetic

monitoring

• USDA Class B vendors• Use of random source

(pound) animals

• Not legal in NJ

Are pets used for research?Class A versus Class B vendors

Animal Welfare

ActPublic Law

89-544 August 24, 1966

VETERINARY SERVICES

Technical services

Small and large animal procedures (fee-for service)

• Operating rooms: email to Dr. Condobery at condobpk@umdnj.edu

• Procedure room: sign-up board across from MSB-A610

• Rodent barrier hoods: sign-up sheets at entrance

• Euthanasia/necropsy room: contact veterinary staff

• Euthanasia, blood collection, treatmentsRequest for Technical Services

• Drug and supply orders: Request for Technical Services, allow 48-hour notice.

General stock is for analgesia, anesthesia, anti-microbial, diagnostic or therapeutic use only: no experimental drugs.

AVMA 2000 Panel of Euthanasia

Specifics acceptable methods of euthanasia

Addresses the following concerns: Humane concerns (good death) Ease of administration Safety for animal and operator Suitability for research goals

VETERINARY SERVICES

Emergency services

• Office and pager numbers are furnished

• A veterinarian is on-call 24/7/365

• Report concerns before they are problems

VETERINARY SERVICES

Consultations & Training

Contact Tracy Davis:email to davista@umdnj.edu

• Barrier training: required for access to rodent barrier

• Rodent surgery: • Euthanasia Training:• Necropsy room: contact veterinary staff

• Euthanasia, blood collection, treatmentsRequest for Technical Services

• Drug and supply orders: Request for Technical Services, allow 48-hour notice; otherwise $15 expedite fee

VETERINARY SERVICES

Drug and supply orders

• Complete Request for Technical Services

• Return to MSB A-610

• Allow 48 hours notice

Calculate drug dose

Body weight (kg) X Dose (mg/kg)Concentration (mg/ml)

DRUG CALCULATIONS

To calculate an individual animal dose, multiply its weight (kg) by the drug dosage and divide by the concentration.

Ex: 25 g x 100 mg/kg10mg/ml

Don’t forget to convert the weight to like units!!!

VETERINARY SERVICES

Drug and supply concerns

Lock all controlled substances.Controlled drugs purchased under the

Research Animal Facility license remain the responsibility of the licensee.

Designate Lab Staff to check drugs every month

Check expiration dates regularly. Return expired controlled drugs to RAF.Discard expired non-controlled drugs.

VETERINARY TECHNICAL SERVICES

Veterinary Technical Staff

4 Senior Veterinary Technicians (nurses) are:

College trained AALAS certified Have several years of experience Attend local and national meetings for

CEC

VETERINARY SERVICES

Chronic care

LARGE ANIMAL • Dental prophylactic dental care• Pedicures• Grooming• Vaccinations• Bloodwork

VETERINARY SERVICES

Chronic care

RODENTS: SENTINEL SURVEILLANCE • Soiled bedding transfer performed once weekly• Leave purple dots on cages• Testing is performed every two months for viruses and

parasites. Most rodent concerns are sub-clinical!• Rodent Room Order is adjusted as needed

e.g. barrier > conventional > necropsy

VETERINARY SERVICES

Adequate care

• Knowledge of and adherence to IACUC protocol• Protocol deviations must be formally amended e.g. new drugs,

new surgeries, change of goals, animal use, animal numbers

• Knowledge of and adherence to Research Animal Facility procedures to provide “adequate veterinary care”

ROLE OF INVESTIGATIVE STAFF

Adequate care

• Knowledge of and adherence to IACUC protocol• Protocol deviations must be formally amended e.g. new drugs,

new surgeries, change of goals, animal use, animal numbers

• Knowledge of and adherence to Research Animal Facility procedures to provide “adequate veterinary care”

ROLE OF INVESTIGATIVE STAFF

Animal illness or pain

Know the condition of the animal before the procedure• Dehydration: report extended skin tenting• Report blood, discharge, soiled discolored

bandages• Report rough hair coats, poor grooming• Report untouched food, water or absence of urine

and feces• Report incision dehiscence (rupture)

Report findings in medical notes (date & initial)

Humane Endpoint vs Experimental Endpoint

• Experimental Endpoint• Planned endpoint when animal will be

euthanized and tissues harvested for in vitro analysis

• Humane Endpoint• Unplanned endpoint (earlier than Experimental

endpoint) if something goes wrong

• Animal must be humanely euthanized if in distress which cannot be treated

ROLE OF INVESTIGATIVE STAFF

Medical record notes (Large animal)

• Shared document• Research lab• Veterinary staff• USDA inspectors• IACUC inspectors

• Record observations, injections, treatments, procedures (date and initial)

ROLE OF INVESTIGATIVE STAFF

Rodent surgical concerns

Pre-operative• Dedicated surgical area• Sterile instruments• Sterile preparation of surgical site• Clean lab coat, sterile gloves, mask required

Post-operative• Warmth• Ambulation• Access to food and water (e.g. sipper tube)• Analgesia

ROLE OF INVESTIGATIVE STAFF

Other rodent concerns

Breeding rodents

Wean at 3 weeks of age

Housing densityFour mice per one shoebox cage

Rats according to weight

Note Rodent Breeding SOP

FACILITY MANAGER

Plans and orders equipmentPhysical Plant: climate-control, plumbing,

drainsTogether with Supervisor manages staffResearch support: special cages, food,

study support Security: keycards and keys

Animal Facility support staff

Administrative staff Animal orders, Billing, Office support

Facility Manager Supervises husbandry/animal care staff

Supervisor and animal care staffVeterinary staff

Husbandry Staff

RAF has 10 Animal CaretakersSeveral are Senior Animal CaretakersSr. ACT requires a minimum of 2 years of

experience and AALAS certificationRAF has 2 Cagewashers RAF has staff working 24/7/365 caring for

our laboratory animals

HUSBANDRY SERVICES

Role of the Animal Caretaker

Daily ROOM evaluation and documentationDaily ANIMAL evaluation and documentationFEED & WATERSANITATIONTREATMENTSMORBIDITY & MORTALITY REPORTING

INTRODUCE YOURSELF!

GOOD ANIMAL CARE PROMOTES GOOD RESEARCH