Equipping a newly renovated ABSL-3 suite with a "smart" biocontainment caging system

摘要 动物生物安全3级（ABSL-3）研究比大流行前增加了近50%，在很大程度上是由SARS引起的- CoV-2研究，目前耶鲁动物资源中心的ABSL-3住房容量已接近极限 （YARC）ABSL-3设施。为了弥补ABSL-3空间短缺，大学资助的425万美元的翻新工程 流行病学和公共卫生实验室（LEPH）8楼动物设施包括恢复两个以前 退役的ABSL-3动物服恢复到最初的ABSL-3用途。翻新LEPH 8 ABSL-3套件，以满足当前 ABSL-3标准将提供进行ABSL-3工程所需的基本标准，但翻修不提供 “移动针头”，走向更有效、更安全的啮齿动物ABSL-3研究。YARC建议装备两架LEPH 8个ABSL-3动物房，共有5个Tecniplast DVC® IsoCage N生物防护笼系统（和1个 旋转器）与新提供的家庭笼监测系统，以充分利用新的ABSL-3套件的使用。这些 “智能”生物防护笼将通过以下方式改变新ABSL-3套件的使用：1）增加额外的水平， 通过带笼的密封负压笼系统实现最大程度的人员保护 高效过滤器。这种额外的笼级保护措施将减少对使用多个BSL-3的担忧 一个房间内的代理，从而最大限度地提高了两个动物房的灵活性; 2）自动评估 笼床条件（湿度）将产生客观数据，用于量化何时需要更换笼。 该系统可消除保持架状况并避免不必要的保持架更换，因为静态保持架通常 每7天更换一次，无论是否需要。通风与自动笼湿度指示器相结合 将笼更换周期延长至14天及以上，特别是对于数量较少和/或较小的笼 小鼠“按需更换”方法通过提供客观的垫料条件数据、潜在的 在换笼期间暴露于BSL-3制剂，减少换笼，并减少废物量 生成（最多减少50%）。湿度指示器系统还将发送紧急警报，如果笼子洪水是 从水源（或其他地方）检测，防止灾难性的动物损失;以及3）自动和 持续监测和分析动物自发运动，从而提高动物福利 监测.由于大多数ABSL-3研究导致与活动水平相关的临床疾病， 远程连续监测活动将彻底改变动物监测。调查人员将能够瞄准时， 需要亲自监测，更好地确定终点，以避免不必要的动物（和数据）损失， 减少与不必要/过度进入相关的非生产性时间和个人风险 ABSL-3空间。综合考虑，职业安全，住房效率和动物监测的严格性将是 增加，而劳动力，PPE和医疗废物处理成本将下降。

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 and medical waste disposal costs will be decreased.