What Constitutes a Good Animal Facility?

What Constitutes ^a Good Animal Facility?

1

Germain Rivard, DVM, PhD

[email protected] [email protected]

[email protected]

1

Institutional Policies and

Responsibilities

- Animals - Users - Public

- Environment

3

Veterinary Medical Care

4

Physical Plant 2

Animal Environment, Housing, and

Management

22 Basic Room/Area Components

• Animal Holding Room

• Procedures Room

• Surgery Area

• Loading Docks [Clean/Dirty]

• Animal Reception

• Feed/Bedding Storage

• Waste Storage

• Waste Disposal

• Washing Room

• Sterilization Room

• Janitorial Closet

• Necropsy

• Office/Reception

• Laundry

• Toilets

• Break & Meeting Rooms

• M echanic al / E lectric al / P lumbin g

• Corridors

• Barriers

• Radiation Shielded /

Imaging Suite

3

Animal Holding Procedures Wash

Sterile Vet

Med Care Admin.

Storage

5 Management Tools

 Primary Barrier [MicroEnvironment]

 Caging

 Personal Protective Equipment [PPE]

 BioSafety Cabinet [BSC]

 Local Exhaust Device [LED]

 Secondary Barrier [MacroEnv.]

 Building

 Floor

 Area

 Enclosure

 HVAC

 Air Ventilation

 Air Pressurization

 Air Treatment

 Standard Operating Procedures [ S.O.P.]

 Budget

Air VENTILATION

• Dilution-Removal

• Single-Pass

Air PRESSURIZATION

+ - Air

TREATMENT

• Filtration

• Temperature

• Humidity

H V A C

CAGING PPE BSC LED

HUSBANDRY

S

O

P

Primary BARRIER

Secondary

BARRIER

$$$$$$

5

AUDIT

• Self / Union

• IACUC Inspection

• USDA

• OPRR

• FDA

• CCAC

• AAALAC

• Energy Audit

• OHSA

• EPA

• CDC

• ADA

• IATA

• ILAR

• LEED

• GVF

Good Animal Facility

Production / Research / Testing / Education Institutional Animal Care

^& Use Program

Health

Well-being / Comfort Safety

– Data: Output/Outcomes

• 3Rs

– Flexibility

– ‘Green’ [Energy-efficiency, Sustainability]

- Animal ^& Occupational Welfare

4 Performance Goals

7

3Rs

• Replacement

– Replace animals with non-sentient alternatives – Use sacrificed animals

– Use non-animal models, training videos, online courses

– Find alternatives to animal use

3Rs

• Refinement

– Reduce the stress on experimental animals – Provide Indoor Air Quality (IAQ) [Room+Cage]

– Improve caging, bedding, feed, water

– Provide novel environmental enrichment – Use the most updated equipment

– Bundling of activities

9

3Rs

• Reduction

The greater the variability, the greater the number of animals the experimenter must use to detect a given biological change.

– Careful planning of experimental design

– Eliminate variables

Fig. 1.1-1 Environmental and management factors affecting animal homeostasis. (After Dr. William J. White) Handbook of Facilities Planning, Vol. 2 Laboratory Animal Facilities, Ed. by Theodorus Ruys, AIA, 1991.

11

Source of Variables

GENETIC

Strains Mutants Tg, KO

HEALTH

Defined Health Status

ENVIRONMENTAL

Engineering Controls

Good Animal Facility

Production / Research / Testing / Education

Stressors

• Noise

• Vibration

• Population Density

• Physical Activity

• Social Interaction

• Bedding

• Nesting

• Enrichment

Disturbances

• Observations

• Intrusions

•Health check

•Watering

•Feeding

•Cage Changing

•Handling

• Attitudes

• Manipulation

• Physical Activity

Conditions

• Feed

• Water

• Light

• Indoor Air Quality [Rm, Cage]

• Air Makeup

• Temperature

• Humidity

• Air Composition

•Oxygen

•Waste Gases

•Odors

•Particulates

• Air Velocity

• Air Ventilation Efficiency or Mixing

• Air Change Rate

• Air Pressurization

Environmental Factors as Source of Variables

13

Air Make-up [Ventilation]

Temperature, Humidity, Air composition [O 2 ,CO 2 ,NH 3 ,Odors]

– Fresh Air at 10-15 AC/h, Total-Cooling-Load Calculation Method – Air Pressurization (+, -)

– Air Treatment (70-90%, HEPA, or ULPA Filter)

Air Mixing Factor or Diffusion Patterns or Ventilation Efficiency

Mixing factor ranges from 1 for perfect mixing to 10 for poor mixing.

Type, Number, and Location of Air Supply and Exhaust Devices - to minimize temperature differential and dead air spaces - to control CO2, NH3, Allergens, Airborne Contaminants

–Recirculation or Dilution-Removal Ventilation

–Single-Pass or Laminar Flow Ventilation

• Recommended-ACH =

Q [exhaust airflow in cubic feet per minute] X 60 V [volume in cubic feet]

Minimal ventilation to accommodate the heat load expected to be

generated by the largest number of animals to be housed plus any heat expected to be produced by non-animal sources and heat

transfer through room surfaces [Total-Cooling-Load Calculation].

• Required-ACH =

Recommended-ACH X Mixing Factor

Adequate ACH to prevent both stagnation and short-circuiting of air, i.e. passage of air directly from the air supply to the air exhaust.

15

How to Determine a Mixing Factor?

• CFD: Predict without resorting to expensive prototyping

• Tracer Gas Simulations: Use rate of decay to calculate AC/h

• CO2

• SF6

• Neutrally Buoyant Helium Bubble Simulations: Show airflow patterns

• Mechanical Engineer

– Smoke Release (Calculate Time for 99% Smoke Removal Efficiency)

Reynolds: 7ppm Isosurfaces of ammonia

SageAction: Clean Room

Supply

12⁰C Exhaust

30⁰C

Location

Equipment Heat Loads

In/Out Air Conduits/Plenums – Horiz./Vert.

Contaminated-Air Recirculation

15 AC/h

144 min. for 99% smoke removal efficiency Poor Mixing Factor [8]

17

Supply

18⁰C Exhaust

22⁰C

Location

Equipment Heat Loads

In/Out Air Conduits/Plenums – Horiz./Vert.

Contaminated-Air Recirculation

15 ACH

7 min. for 99% smoke removal efficiency

19

The longer the exposure; the higher the number of potential variables!

+/- 0.15 m/s

IVC

EVC

60 ACH

20 min.

20 ACH

4 min.

Poor Mixing Factor

• Small diameter air valve or nozzle = High Frequency Noise

• Turbulences, Drafts, and Dead-Air Spaces = Poor Air Mixing

• 20^oC [68^oF] air moving at 0.3m/s[60 fpm] = Evaporative Cooling Effect of 7^oC [12.6^oF] +/- 0.5 m/s

• High-Velocity : 0.3 – 0.5 m/s [40-100 fpm ], 60- 120 AC/h

+/- 0.3 m/s

• Low-Velocity : 0.02 – 0.15 m/s [4-30 fpm ], 20- 100 AC/h

• Large vent port = No Noise

• No Drafts = Fair to Near-Perfect Air Mixing

• Low Velocity = No Cooling Effect

+/- 0.1 m/s

+/- 0.15 m/s - 0.02 m/s - 0.02 m/s

21

• Noise

1. IVC Fan

2. Cage Changing Station

3. Air supplied through Small Valves 4. Room Air Diffuser

√ √ 55 dB

√ √ 84 dB

√ 60 dB

√ 75 dB

Noise Level

High-Frequency

Low-Frequency

Human Mice

0.02 – 10 – 20 – 30 – 40 – 50 – 60 – 70 – 80 – 90 – 100 kHz

Ultrasound: Echolocation, Alarm calls, Pup distress calls, Social/Sexual interactions Ultrasonic Songs of Male Mice: http://tinyurl.com/7s3te

Timothy E.H. and Zhongsheng G., Depart. of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri. PLOS Biology, Vol 3, Issue 12, 2005.

Between 32 and 62 kHz: Repulsive to Rodents ( PestChaser induces auditory stress)

Recommended Maximum Noise Level for

Human: BELOW 85 dB Rodent: BELOW 50 dB

Noise exceeding 83 dB may reduce fertility of rodents

23

• Noise

• Vibration

2. Environmental Factors

Human Mice

• Vibration

Blowers on wall brackets fail to stop vibration in the cages as it is probably due to

the high-velocity and small volume of air conduits on the rack.

Static [ SMI ] Ventilated (Forced-Air) IVC Ventilated (Exhaust-Air) EVC

EVC cages did

not exacerbate the symptomatology of MHV compared to SMI and IVC

• Clinical signs, severity of symptoms, and survival are affected by the caging system

• Caution should be applied when extrapolating data from different caging systems

Effect of Caging System on a MHV-model of Experimental Infection

2004, JC Gourdon, DVM, LE Guanzini, LATg, JD Baines, DVM, PhD, MM Bailey, DVM, DACLAM, Cornell University. CARE. Ithaca, NY 14853

25

• Enrichment

Joe Garner, PhD, Purdue U., Lafayette, IN

2003, Can we trust research done with lab mice? Discover 24(7): 64-71 2002, Animal models - Can a mouse be standardized? Science, 298 2001, Animal data jeopardized by life behind bars. Nature, 412

Barbering (stereotypy

Schizophrenia

• Enrichment structures or nest building material [paper towel] that can be ‘shared’

avoid agonistic behaviors and variables

• Burying / Tussling / Biting enrichment devices are aversive and aggressive responses, not play!

• Defensible enrichment devices (shelters) cause territoriality, aggression, and stereotypy

Prevent the alteration of biological, behavioral, or health status.

1. Provide similar room conditions in the cage.

2. Prevent evaporative cooling effect/avoiding eddys, drafts, dead air spaces.

3. Avoid noise and vibration in the cage.

4. Eliminate recirculation of heat loads, moisture, waste gases, and particulates at the room and cage levels.

5. Preclude expression of stereotypic behaviors (barbering, cannibalism) using nesting materials, enrichment structures and IAQ.

6. Fail to exacerbate the symptomatology of metabolic changes.

Good Animal Facility

Production / Research / Testing / Education

27

Eliminate variables to allowing the production of valid data.

Reduce the number of animals needed for statistical significance.

Flexibility

• Conventional

• In/Out

• Barrier

• I

• II

• III

• IV

• Containment

• ABSL 1

• ABSL 2

• ABSL 3

• ABSL 4

• Mouse

• Rodents

• Rabbits

• Dogs

• Non-Human Primates

• Multi-Species

• Farm Animal

• Others

Environmentally-Responsible

• Sustainable / ‘Green’

29

Energy Conservation, Water and Waste Reduction

Recognize Green Initiatives ^that Encourage Sustainable Use of Space, Materials, Resources [Water,Electricity].

A Resource for Green Design & Planning,

Reduce Energy and Water Consumption, Decrease Waste Disposal,

Increase Indoor Air Quality.

30

Green Vivarium Foundation

•

 Evidence-Based Information

Concept including Theory and History

Data for Metrics

 Electricity – Gas – Water – Waste - Others

 Occupational Health and Safety

CO2 – NH3 – Airborne Contaminants - RODAC

 Animal Care and Use

CO2- NH3 – Airborne Contaminants – Breeding Performances – Population Density - Sentinel

 Cost Analysis with Payback

Case Study

Green Practices ⁱⁿ

Vivaria

31

The Green Vivarium Foundation 1 ^st Annual Awards-2008

 Best Individual Initiative

 Carrie Grace, National Jewish Health Biological Resource Center, Denver, CO

 Initiated a recycling and energy, water, and waste reduction program

 Non-secure paper products and water bag [optimize changing periods]

 Best Facility

 NIH Mouse Imaging Facility

 Converted to a recyclable cage system that saves energy and space

 Best Product or Service

 Innovive, San Diego, CA [www.disposablecages.com]

 Innocage and Innorack disposable technology eliminates the need for on-site washing/sterilizing

 Save energy, water, and space

The Green Vivarium Foundation 2 ^nd Annual Awards-2009

 Best Individual Initiative

 Professor Dr. Joerg Schmidt, Helmholtz Center Munich, Germany

 Initiated a Waste Separation Program for Plastics

 Prevented 69,000 Kg of CO2 production related to transport, shredding, recycling

 Best Facility

 Pfizer, St. Louis

 Low environmental burden at the landfill during construction

 Tri-level HVAC mode: Occupied [15 Ach, 12:12], Unoccupied [3 Ach, OFF], Decontamination [0 Ach, OFF]

 Best Product or Service

 Beta Star Life Science Equipment, Honey Brook, PA [www.rvii.com]

 Enviro Vac: Water Conservation Vacuum system

 Circulate and re-use water in a condenser tank to save up to 80% of water per cycle

33

Energy-Efficient NYSERDA Grant

3 Green Strategies to Save 70% Energy

□ Reduce Animal Space to Air Condition

□ Shift from Dilution-Removal to Single-Pass Ventilation

□ Recover Energy from Exhausted Conditioned Air

Reduce Animal Space to Air Condition

□ 6,000 cages: 3,750 sf [1.6] 1,800 sf [5.7]

□ Reclaim Space [2,700 sf or 72%]

□  $ Architectural &Engineering [76%]

□  Maintenance [65%]

35

Recover Energy from

Exhausted Conditioned Air

□ Heat Pump Heat Recovery

□ 3,200 cfm/6,004 LED [12 kW] = 65% Recovery

Shift from Dilution-Removal to

Multi-Point Exhaust [Single-Pass] Ventilation 12,000 cfm [19 AC/h] 3,200 cfm [9 AC/h]

□ Local Exhaust Devices [6,004]

□ Exhaust Ventilated Caging System (EVC)

□ Downdraft Workstation

□ Low-Pressure-Drop System

3 Fabric Air Distribution Ducting Diffusers 64 Manifolded Local Exhaust Devices

6,000 Cages

EVC+

LPD, HR First Cost

Savings (%)

$728,250 $175,650

$552,600 (76%)

HVAC & Plug Load [kWh] 356,800 98,800 (72%)

Carbon Footprint: CO2

- Savings

271 tons 75 tons

196 tons

Annual Energy Cost

- Savings (%)

$ 88,500 $ 11,652

$76,848 (87%) Annual Maintenance Cost

- Savings (%)

$22,200 $ 7,800

$14,400 (65%) Annual Husbandry Costs

- Savings (%)

$660,000 $576,000

$84,000 (12%)

perDiem/cage Cost

- Savings (%)

$0.38⁷

$0.28¹

$0.10⁶ (26%)

Costs and Benefits of Green Technologies

$232,140/yr

37

Wood

Molding Recycled

Fiber Molding

• Stack-driven

• Lighting

Gas

• Plug-in

ELECTRICITY HEAT

• Air Conditioning

W2E

PEV

Convection

Turbine-Generator Bedding ^●● Cage

BioWaste

PPE

Processing

Reduce the flow of air, water, and waste to help fight global warming

Eliminate plastic use to curb oil dependency