ABSTRACT Animal Biosafety Level 3 (ABSL-3) studies have increase nearly 50% from pre-pandemic, in large part, by SARS- CoV-2 research and is now nearing ABSL-3 housing capacity limit in the current Yale Animal Resources Center (YARC) ABSL-3 facility. To remedy the ABSL-3 space shortfall, a $4.25M university-funded renovation of the Laboratory of Epidemiology and Public Health (LEPH) 8th floor animal facility includes restoring two previously decommissioned ABSL-3 animal suit to its original ABSL-3 use. Renovating LEPH 8 ABSL-3 suite to meet current ABSL-3 standards will provide basic criteria required for conducting ABSL-3 work but the renovation does not “move the needle” towards more efficient and safer rodent ABSL-3 research. YARC proposes to equip two LEPH 8 ABSL-3 animal rooms with a total of five Tecniplast DVC® IsoCage N biocontainment cage system (and one rotator) with a newly available home-cage monitoring system to fully leverage use of the new ABSL-3 suite. These “smart” biocontainment cages will transform use of the new ABSL-3 suite by 1) adding an additional level of biocontainment for maximum personnel protection through sealed, negative pressure caging system with cage level HEPA filtration. This additional cage level safeguard will lessen concerns over the use of multiple BSL-3 agents within one room, thereby maximizing the flexibility of the two animal rooms; 2) automated evaluation of cage bedding conditions (wetness) will result in objective data that quantifies when cage changing is required. This system standardizes cage conditions and avoids unnecessary cage changes, given static cage are typically changed on a 7-day cycle, regardless of need. The ventilation combined with automated cage wetness indicator will extend the cage change cycle to 14 days and beyond, especially for cages with lower numbers and/or smaller mice. The “change on demand” approach reduces labor by providing objective bedding condition data, potential exposure to BSL-3 agents during cage changes from reduced cage changes and decreases the amount of waste generated (up to 50% less). The wetness indictor system will also send emergency alerts if cage flooding is detected from the water source (or otherwise), guarding against catastrophic animal loss; and 3) automatic and continuous monitoring and analysis of spontaneous animal locomotion resulting in enhanced animal welfare monitoring. Since most ABSL-3 studies result in clinical disease that correlates with activity levels, the ability to continuously monitor activity remotely will revolutionize animal monitoring. Investigators will be able to target when in-person monitoring is needed, better pinpoint endpoints to subvert unnecessary animal (and data) loss and decrease the amount of unproductive time and personal risk associated with unnecessary/excessive entry into ABSL-3 space. Taken together, occupational safety, housing efficiency and animal monitoring stringency will be increased while labor, PPE an...