Improving Animal Model Translation, Welfare, and Operational Efficiency with Appropriate Housing and Infrastructure Design
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Digital monitoring systems can help optimize animal housing and infrastructure design to improve animal welfare, data reproducibility, and operational efficiency. Such systems allow near real-time tracking of animals, detection of issues like water flooding, and analysis of the effects of procedures on animal activity levels. This can help reduce cage change frequencies and the associated space needed for wash areas. Real-time air quality monitoring also enables reduction of conditioned supply air levels while maintaining animal health standards, reducing energy costs significantly. Overall, digitalization provides opportunities to standardize data collection, minimize confounding factors, and enhance the rigor and reproducibility of research.
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Improving Animal Model Translation, Welfare, and Operational Efficiency with Appropriate Housing and Infrastructure Design
- 1. Improving Animal Model Translation, Welfare, and Operational Efficiency with Appropriate Housing and Infrastructure Design Dr. John J Hasenau Principal, Lab Animal Consultants Jeffrey Zynda Principal, Science and Technology Perkins+Will
- 2. Improving Animal Model Translation, Welfare, and Operational Efficiency with Appropriate Housing and Infrastructure Design John Hasenau, DVM and Jeffrey Zynda consider practical options for housing and infrastructural designs to sustainably improve animal welfare, data reporting and reproducibility through the use of new technologies used by academia, pharma and CROs to acquire animal activity data.
- 3. InsideScientific Webinar Improving Animal Model Translation, Welfare and Operational Efficiency with Appropriate Housing and Infrastructure Design Part 1: Recent Housing improvements and Equipment Developments that Improve Repeatability and Rigor of Data Reporting John J. Hasenau DVM, DACLAM Part 2:Next-generation strategies to maximize laboratory space efficiency, flexibility and productivity. The Value of Digitalization in a LAS Facility from the Architect’s point of view. Mr. Jeffrey R. Zynda, Regional Science Practice Leader, Principal Perkins & Will
- 4. Current Rodent Housing, Needs From the Management and Research point of view Dr. John J Hasenau Principal, Lab Animal Consultants Labanimalconsultants@charter.net
- 5. Welcome #1 • Management Needs: - Increased density while maintaining footprint - Ability to have good tracking and monitoring of animals in near real time. - Promote animal welfare at all levels and maintain staff engagement. - Keep costs contained and promote sustainability in operational efficiencies
- 6. Welcome #2 • Research Needs: - Have translatable data, which may include repeatability and rigor. - Ability to have good tracking and monitoring of animals in near real time - Promote animal welfare at all levels for improved data translation - Keep costs contained and promote sustainability in operational efficiencies
- 7. Key Objectives • How to improve the translational value of animal models through advanced housing systems • Optimizing Animal Welfare with advanced housing systems • How can locomotor activity serve as a “digital biomarker” for animal welfare for infectious disease • Use of an automated home housing systems to improve standardization of the cage and decrease human associated factors of study disruptions • Use of automated housing systems to eliminate shared instrument behavioral, physiological, and in general study disruptions • Why digitalization of a facility is now mandatory than elective from a design aspect • Practical relevant information that you (the participants) can use at your facilities
- 8. Introducing Study Data Reproducibility • Reproducibility Definition- the replication of results through independent experiments. • Best done with rigorous and transparent experimental methods. • Stages that impact this: – Experimental Design – Methodology – Analysis – Interpretation – Reporting
- 9. ARRIVE (Animal Research Reporting of In Vivo Experiments) Guidelines on Housing and Husbandry. • Original 2010: • Updated 2019: included as Recommended List vs Essential 10 (Study Design, Sample Size, Inclusion and exclusion criteria, Randomization, Blinding, Outcome Measures, Statistical Methods, Experimental Animals, Experimental Procedures, and Results) which allows journal staff, editors, and reviewers to verify items adequately reported in manuscripts.
- 10. Current Issues: Specifics to Housing and Husbandry • Macroenvironmental Concerns • Microenvironmental Concerns • Study Conductivity
- 11. • Temperature • Humidity • Light • Air Flow • Differential Pressure CONDUCTANCE GUIDELINES: Per The Guide, areas that need to be monitored in a typical environment: Macroenvironmental Concerns
- 12. Micro environments for Rodents in Laboratory Animal Facilities. • Rodent Cage Level Temperatures • Rodent Cage Level Humidity • Rodent Level Air Flows • Rodent Level Lighting • Rodent Level Noise • Rodent Level substrate (contact bedding) • Related Husbandry items: – Nutrition (diet) – Water – Cage housing items (EE) – Animal handling
- 14. Rodent Housing Varieties • Types: Open top, Closed top, Microisolators (non- ventilated, ventilated), Automated home cage systems… • Sizing differences within manufactures as well as throughout the industry • Color of Units (affects on circadian metabolic measures, melatonin variations) • Unit Compositions (polypropylene, polycarbonate (BPA), polysulfone (BPS), and polyphenylsulfone) • IVC-Where is air supplied, at what rate(s), positive or negative to the room?
- 15. Rodent Housing Varieties; types
- 16. High-Density Housing 20% more housing density in the same footprint, 96 housing units in single sided racks (vs 80) and 192 units in double sided racks (vs 160). Built in Environmental Enrichment.
- 17. Rodent Housing Varieties; types Different automated home housing systems: Video based, Infrared based, sensor plate, RFID, nose pokes with instrumental monitoring, Electrode capacitance perturbations as examples.
- 18. Digital Ventilated Caging (DVC) utilizes EMF/ELF for automated home cage monitoring
- 19. DVC® System Working Principle
- 20. DVC® algorithms The DVC® system collects data 24/7 and applies different algorithms based on the different available features * LDS algorithm example • Anomaly Animal Activity • Bedding Condition Analysis • Food Availability • Water Bottle Availability • Water Flooding detection • No activity from registered cages • Activity from unregistered cages • Activity from an empty position (not properly inserted cage) • …
- 21. Rodent Housing Systems; colors & light control
- 22. Not a new concern for the industry
- 23. Rodent Caging Varieties; IVC air supply Highlights - Balb/c and C57BL6 mice behaved differently in two anxiety behavior tests when housed in two different IVC systems with different air supply. - In one system, air was delivered at cage cover level, while in the other, air was delivered at cage level. - In the system where air was delivered at animal level, the mice exhibited more anxiety-like behavior in the open field and elevated plus maze tests.
- 24. Handling of Animals Alternatives to tail handling • Tube movement – when properly trained and performed in high anxiety mice improved performance reliability in habituation- dishabituation behavioral testing • Cup movement – as above Professor Jane Hurst, University of Liverpool NC3R’s
- 25. Handling of Animals Individual responses • Female mice sensitivity to male experimenters (but not male husbandry personnel) causing a robust stress- related analgesia effect
- 26. Cage Changing and animal movements • Use of Continuous Automated Home Cage Systems to determine impacts • Range of impacts with cage changing are 48-96 hours post changing, dependent on room size and procedures, strain, sex and time of day of cage changing • Primary impacts are seen during the daytime activities • Age dependent changes were not seen
- 27. Continuous Automated Home Cage Monitoring and Cage Changing effects
- 28. Cage Changing or movement of animals out of the home cage for experimental manipulations - automated home cage analysis Day Night day 0 day 1 day 2 day 3 day 4 day 5 day 6 Bedding change Mice weighing Effects of procedures such as • bedding changes • Weighing • Lights ON/OFF
- 29. Global Animal handling and Bedding change effects on animal activity Heat maps • Global activity during 4 consecutive weeks Each panel is 1 week • The white vertical line indicates transition to night time with lights-off • Cages were not removed from the rack but daily checked • Two weekly intrusive procedures were conducted (cage-change- Thursdays, weighing and a handling health assessment on Monday) • Day and night rhythm of activity and impact of procedures replicate well across all geographic sites
- 30. Continuous Home Cage Monitoring as a tool • Allows behavioral and physiological monitoring of animals with minimal or no human intervention or bias • Increases the understanding of the normal diurnal behaviors and activities • Explore how environmental manipulations interact with genetics and age • Understand the magnitude and duration of procedure effects • Potential to increase study reproducibility
- 31. Night Welfare Check – Alert (E-mail) Current night analysed vs. previous nights (activity) Cage Score(s) assigned if obvious changes are detected E-mail will be generated and sent to the assigned person for check Examples of welfare score: • Anomalous hypoactivity • Anomalous hyperactivity • Circadian rhythm disruption
- 32. Example: water flooding effect Big and fast drop of the Bedding Status Index due to the water flooding (17° Sept at 01:32am)
- 33. Reduced almost to “zero” activity Example: water flooding effect Zooming the period and using a more detailed minute aggregation visualization in the DVC® Analytics we can see that, immediately after the water bottle flodding occured, the animals dramatically reduced their spontaneous locomotion around the cage until the cage itself was “rescued” by operators in the morning (changed)
- 34. Cage Change event Example: water flooding effect
- 35. Now, looking at a wider temporal period including 2-3 days after the water flooding, it is extremely evident how much time the animals needed to really fully recover. The entire day (light) and night after the event, although now the cage was already back to “standard” conditions, shows that in reality the animals were still “under shock/stress” because the circadian rythm not yet fully recovered (in comparison to days before the event). Cage change 1.5 days impact Example: water flooding effect
- 36. Embryos cryopreserved @ Jax Currently studied Why is ACE2 receptor important for Covid19 entrance? Animals kept 5 years then culled SARS-CoV-2 (Covid19) Mouse Models
- 37. Body Weight https://www.nature.com/articles/s41590-020-0778-2#Sec10 SARS-CoV-2 (Covid19) Mouse Models
- 38. Body weight start to change when activity is already depressed to 10% * Data generated as courtesy of Univ. of Montreal, MUHC (BSL-3) DVC® in infectious disease: SARS-CoV-2 (Covid19) mouse models Method: n=8, (2.8x104 TCID50/ml) 6 days observation post inoculation, parameters body weight % (gold standard) and distance travelled % Hypothesis: What are the effects of Covid19 inoculation?
- 39. Biocontainment studies using hermaticaly sealed housing systems (ISO-N)
- 40. Provides opportunities for reduced cage handling and unique advantages: Research Facility management Animal Welfare Keep the animals in their home cage: reduce animal and cage handling that enhances bio-safety 24/7 locomotor detection for a better daily animal welfare check Reduce the Bedding change Automatic flooding detection 24/7 locomotor data collection for more reliable data High throughput data (all the experiment cages together) minimize possible confounding factors Provide standardized metrics: just keep the animals in the home cage and automatically collect results (reduced bias), improvement of longituditinal data collection. DVC® for ISO: Automated 24/7 data collection from the home cage
- 41. Provides opportunities for reduced cage handling and unique advantages: Research Facility management Animal Welfare Keep the animals in their home cage: reduce animal and cage handling that enhances animal welfare 24/7 locomotor detection for a better daily animal welfare check Reduce the Bedding change Automatic flooding detection 24/7 locomotor data collection for more reliable data High throughput data (all the experiment cages together) minimize possible confounding factors Provide standardized metrics: just keep the animals in the home cage and automatically collect results (reduced bias), improvement of longituditinal data collection. DVC® for High Density Housing (Emerald): Automated 24/7 data collection from the home cage
- 42. - THANK YOU -
- 43. Vivaria in the Age of Data-Science LK;LK Jeffrey R. Zynda | Regional Science Practice Leader, Principal jeffrey.zynda@perkinswill.com Challenges and Opportunities of Digitalization of Animal Facilities
- 44. Introduction Facility Optimization Energy Reduction Design Considerations Agenda 44
- 45. “…Uphold the scientific rigor and integrity of biomedical research with laboratory animals as expected by their colleagues and society at large…” - 8th Edition of ILAR “Guide”
- 48. Challenge 48 The use of digital monitoring of cages for optimized change rates can theoretically decrease the cage change rate and the associated the amount of space allocated for wash operations potentially reducing construction and operational costs.
- 49. Facility Optimization 49 8,000 cage – Mice 1,500 tank - Aquatics 500 cage - Rabbits
- 50. Facility Optimization 50 8,000 cage facility – weekly full cage wash – 1,600/day 650sf (56m2) – Soiled Side 550sf ( 46m2) – Clean Side 1,200sf (112m2) – Total Wash
- 51. 8,000 cage facility – weekly full cage wash – 1,600/day 650sf (56m2) – Soiled Side 550sf ( 46m2) – Clean Side 1,200sf (112m2) – Total Wash Facility Optimization 51 1,200sf@ $1,400/sf = $1.68MUSD
- 52. Facility Optimization 52 Original Change Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Percentage Reduction Housing #1 1/week – Cages 15% 14% 55% 57% 55% 60% 43% Housing #2 1/week – Cages 6% 7% 44% 52% 53% 50% 50% Housing #3 1/week – cages 2% 2% 43% 44% 45% 45% 56% * *After two months the cage change duration was switched from one to two weeks
- 53. Facility Optimization 53 Original Change Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Percentage Reduction Housing #1 1/week – Cages 15% 14% 55% 57% 55% 60% 43% Housing #2 1/week – Cages 6% 7% 44% 52% 53% 50% 50% Housing #3 1/week – cages 2% 2% 43% 44% 45% 45% 56% * *After two months the cage change duration was switched from one to two weeks It was determined through home cage monitoring that the change rate and associated space could be reduced by approximately 50%.
- 54. Facility Optimization 54 840sf @ $1,400/sf = $1.2m USD Ultimately it was decided that the throughput workspace could be reduced by 1/3 because of a longer cage change duration / through – Saving $504,000 USD.
- 56. Challenge 56 Real-time digital monitoring of air quality and conditions can result in significant reductions in conditioned supply air while maintaining safe and repeatable baseline conditions for animal health, welfare and scientific discovery.
- 57. 57 Energy Use Reduction Typical laboratory ventilation 6 ACPH @ 10’-0” ceiling is ~ 0.02M3/Sec/Min (1 CFM / SF) ILAR “Guide for the Care and Use of Animals” “Provision of 10-15 fresh-air changes per hour in animal housing rooms is an acceptable guideline to maintain macroenvironmental air quality by constant volume systems and may also ensure microenvironmental air quality” – 10-15 ACPH = ~ 0.05M3/Sec/Min (2 CFM / SF) FELASA Euroguide 2007 / ETS 123 In each room, 15–20 air changes per hour is normally adequate but can be reduced to 8–10 if stocking densities are low. 15-20 ACPH = ~ 0.07M3/Sec/Min (2.5 CFM / SF)
- 58. Energy UseReduction 58 19% 14% 9% 46% 8% 4% Plug Loads Lighting Pumps & Fans Heating Cooling Other
- 59. Energy UseReduction 59 19% 14% 9% 46% 8% 4% Plug Loads Lighting Pumps & Fans Heating Cooling Other 63%
- 60. Energy UseReduction 60 Demand Controlled Ventilation (DCV) is perfectly suited foranimal facility applications Modulation of airflow can provide as little as 4-5 air-changes-per-hour that can beelevated based on room conditions (8-10 ACPH). Sensors can be calibrated tosense: • TVOC’s • Airborne Particulate • Ammonia
- 63. Energy UseReduction 63 Continuous digitalair-qualitymonitoring allows forreduction inairflowfrom 15-20 air-changesper hourto 4-6 air-changes per hour, whilemaintaininghigh-qualityconditions for the animals. 60-75% air-side energy savings is attainableusing demand controlled ventilation(DCV)systems.
- 64. Energy UseReduction 64 Institutions that choose todeviate from15-20 airchanges per hour (CCAC,2003) must providethe infra-structure, monitoring, control mechanism, anddocumentation necessary toensure appropriateairquality at all times for animals andpersonnel, as specifed in this document.
- 67. Challenge 67 Set cage change rates from past metrics led to unnecessary handling of animal andhigher than required labor forcage movement as wellas wash operations. Labor couldbe optimizedthrough monitoring of cages and using automation inwash operations to allowstaff to be re- tasked toward research support roles.
- 68. Challenge 68 4 Month study of 600 cages yieldedresults that showed approximately 40-50% of the cages did not needto be changed at 14 days, via digital monitoring. The theory was that labor could be reconsidered for changingoperations, cage movement andwash operations.
- 70. Labor Optimization 70 10,000 cage facility –WeeklyWash Schedule = 2,000/day
- 73. Labor Optimized 73 Reducedwash throughputrequired- ~600/day
- 74. Finding 74 Cage changes occurredin a range of 18-24 days and resulted inthe re-taskingof four people for cage change and movement. Wash related labor reductionsallowedfor the re-taskingof eight people for both soiled andclean-sideoperations.
- 76. Design Considerations 76 3350mm x 7600mm =22m2 11’-0” x 22’-0” =240 nsf Six single-sided rodent cage racks =460-480 cages /room Stock density of 5 rodents per cage yields: 2,300 models per room
- 79. Design Considerations 79 CablingCategory CAT 3 CAT 5 CAT 5e CAT 6 CAT 6a Maximum Data Rate 10 Mbps 100 Mbps 1000 Mbps 10 Gbps 10 Gbps Maximum Frequency 16 Mhz 100 Mhz 350 Mhz 250 Mhz 750 Mhz TypicalDistance 100m(50 Actual) 100m(60-70 Actual) 100m(50m actual) 100m (55m Actual) 100m (60m actual)
- 82. Design Considerations 82 Protocol Theoretical Actual 802.11b 11Mbps 5.5Mbps 802.11a 54Mbps 20Mbps 802.11g 54Mbps 20Mbps 802.11n 600Mbps 100Mbps 802.11ac 1,300Mbps 200Mbps
- 83. Design Considerations 83 1 Gbps translates into about 125 megabytes per second (MBps). 1 720p video feed requires approximately 25MBps. = 7.0GB/Hour.
- 90. Summary 90 • Digital home cage monitoringshows great potentialtomodify traditional laboratory planning metrics for wash operationsand associated construction cost savings. • Digital environmentalmonitoringcan significantlyreduce energy usage in vivaria. • Using digitalmonitoringin conjunction with automationcan allow labor to be re-tasked tosupport animalcaretaking and research. • Digital home cage monitoringtakes variousforms – know how they work and what constraints youhave in your facility!
- 91. • Watch the webinar here: Improving Animal Model Translation, Welfare, and Operational Efficiency with Appropriate Housing and Infrastructure Design • Want to learn more about the DVC system from Tecniplast? Visit: www.tecniplast.it Thank you!