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So, is more always better?

After review of many animal facilities, there appears to be no norm for the number of racks of mouse boxes in animal holding rooms for a standard vivarium. A range is found anywhere from 3 – 20 racks per room, each holding from 98 – 160 cages per rack. Although some rooms may have <3 or >20 racks, most commonly the number of racks will be found within these limits. One might ask if there is an optimum for the number of racks per animal holding room (AHR) and, furthermore, if that norm is the same or different from an animal care technician’s perspective, researchers and their staff, veterinary and health surveillance technicians, consideration of “green” utility efficiencies, or from any number of other criteria. Interestingly, the number of cages indexed to usable square feet within such a range of racks per room varies within a relatively narrow range, that being between 2.0 – 3.0 cages per AHR net square foot. While this value is impacted by the number of cages per rack, it remains notable that the values have a small range. Figure 1 illustrates two different room configurations with widely different cage capacities ranging from fewer than 1000 to greater than 5000 cages per room; yet, the room density, i.e., cages/usable square foot, ranges only from 2.2 – 2.8 cages/net square foot.

The Four Constituencies
If, then, there is no overwhelming difference in the number of cages per square foot in rooms substantially different in overall dimension, what might be the relevant criteria to determine if there is an optimal room size to accommodate research with laboratory mice? To begin, it is important to consider the priorities of those individuals with a vested interest in the eventual configuration. Though they may be complementary, some concerns may be conflicting, and the design team needs direction to develop plans that will hopefully satisfy the different interests. Primary concerns are usually expressed by four constituencies (Table 1): the Investigators and their personnel whose mouse-based research will be accomplished within the rooms, the Lab Animal Resource team, whose responsibility is for the day-to-day operation of the facility, the Veterinary Medical Staff, ensuring the health of the animal populations, and the institution’s administration who define the scope and dimension of the animal care program.

The determination of available space (i.e., net square feet, nsf) within any AHR will be affected not only by dimensions, but by the inclusion of several fixed and non fixed structures and equipment. These may include, but not be limited to sinks, fixed load-bearing columns, floor drains with associated pitch, biosafety cabinets and mobile cage change stations, extra caging, rodent chow, consumable supplies, personal protective equipment and cage handling equipment (carts, clean cages, etc.), records and documents in active use, investigator-related devices and materials (e.g. telemetry platforms, metabolism cages, treadmills, recording equipment, scales, drugs, experimental agents, special diets), and waste collection receptacles that may not occupy floor space all the time but must be considered since they will impact accessibility at some regular interval. Room to work is necessary for both animal care staff and research personnel, resulting in a reduction in usable square footage for racks of cages.

The number of investigator staff accessing the AHR will be influenced by the type of research being accomplished. This influence is represented in Table 2. In study programs with large breeding colonies of genetically altered mice, only a few investigators (occasionally even just one) may have in excess of 3000 cages being managed by only a very few research technicians. Alternatively, studies of experimental pathology and therapeutics could involve tens of technicians, students, postdoctoral fellows and others with necessary access to an individual AHR. As well, procedure rooms and specialized technologies outside the AHR, such as imaging or irradiation, will result in a regular stream of traffic out of and back into the AHR. Certainly, the fewer cages per project, the greater the likelihood that an associated larger number of research staff will require access. The larger the room, the more traffic; the more traffic, the more disturbances there will be to the room, its occupants, and its activities.

The facility operations staff also requires access on a regular basis. If one accepts a cage change frequency for individually ventilated cages with auto water of every 14 days, and a cage change rate for individually ventilated cages (IVC, microisolators) by technicians of about 30-35 cages per hour, then a room holding between 1800 and 2400 cages will have a facility person in the room and continuously using the biosafety cabinet/ change station essentially every hour of every day of the work week. Not only that, additional space will be required for clean changeout cages, other support supplies, soiled cages, other soiled items, and waste. Any more cages than this will require and result in more than one care tech in the room all day every day. This scenario, of course, only accounts for animal care procedures; research personnel during these times will require convenient and regular access to the room, their animals and a biosafety cabinet.

Weighing the Factors
Eventually, all considerations will impact animal health and welfare. Concerns of noise, vibrations, cage and rack movements, continual movement in and out of the room of different personnel, handling and opening of filter top cages all have potential impact on animal health. Further, a health assessment program comprised at the least of sentinel mice with soiled bedding exposure and daily visual health checks becomes much more complex as cages and racks become more compressed and the census per net square feet surges to a detrimental ratio. This presents compelling challenges not only to the veterinary staff, responsible to assure the health status of the colony, but also to husbandry personnel tasked with conducting the soiled bedding exposure procedures. The veracity of sentinel programs may be compromised when it is difficult to work in tight spaces and the work of exposing sentinels to soiled bedding may not be done.

The presumption in providing a wholesome and consistent environment where animals reside and studies are conducted is that a limited number of individuals accessing the AHR is desirable.The less disruption, the less noise there will be; the less noise, the better for both animal welfare and the environmental consistency critical to data collection; the fewer people accessing the AHR, the less risk of contamination, confusion, compliance failures, and conflict. This results in a general consensus that an optimum may exist for the number of racks/cages per AHR (Table 3).This is necessarily balanced with the conflicting consideration that construction costs will be reduced the greater nsf one can dedicate to actual and realized single AHR. Air handling costs, controls, security, lighting, etc. are all less expensive if larger individual AHR are designed. That is, the maximum cages per net square foot within the largest rooms translate to lower construction costs on a cage per facility net square foot basis.

This, then, raises a dilemma for the design team. What constituencies are represented at the design table? Whose voice will prevail? Is upfront construction cost containment the only or most prevailing criterion for consideration? How much weight should be accorded to animal care operational efficiency and the minimization of operating costs over the lifetime of the facility? Do the needs of scientists to manage and supervise their employees, have convenient access to animals, produce data and generate important findings merit any consideration in this context? Who is the real client as the facility is designed? All four represent perspectives with vested and often conflicting interests. For example, while a single facility with a few spacious rooms might be favored by the administration and animal resources program because of the likelihood of low construction and operating costs, small rooms dedicated to each laboratory and in decentralized and dispersed distribution convenient to laboratories would be preferred by scientists.

Change is the Only Constant
A large room may contain nearly 6,000 cages while, if divided into several smaller AHR, collectively occupying nearly an equivalent footprint, fewer than 4000 cages may be held (Figure 1). This loss of 2,000 cages merely by erecting a few walls illustrates the practical reality that larger rooms mean more cages within a greater footprint. However, the success of the larger design in terms of environmental consistency and the minimization of disruptive events rests on the fact that only a very few investigators occupy the larger rooms. Of course, this is satisfactory while they are tenants maintaining a large census. However, if their funding decreases, they change program direction, or, as is not uncommonly the case, they are attracted to another institution, the large rooms now are most likely required to meet the needs of several smaller users, compounding the problems of access, disturbance, and constant use. Traffic to and from external procedure spaces becomes more of a problem in this multi-user AHR scenario, as does the consideration of what procedures are permitted within AHR. That issue rests with the institution and typically with its institutional animal care and use committee (IACUC). Some IACUCs will allow quite a bit in a room in this regard. Others permit no experimental procedures, no manipulations in the animal room at all. This will impact how many procedure rooms are needed as well as the associated animal and personnel traffic to and from them. Investigators sharing procedure rooms also can present concerns when there are large numbers of them and their staff per AHR. They not only share the animal husbandry space, but they also share the procedure space.Many research groups use expensive equipment and tools. Shared space can present a security challenge, not only with regard to other research groups, but also with the facility staff who normally are required to maintain and clean that space. Even schedules for use can present problems: the more users, the greater the potential for problems and often the greater need for active oversight and scheduling by management resulting in additional operating expenses.

The consideration that eventually AHR will have different occupants with very different needs, compounded by the variable that today’s mouse room may be tomorrow’s zebrafish, rabbit, ferret, or non-traditional species room adds weight to the argument in favor of smaller sized rooms permitting greater facility flexibility. Larger AHR have restricted plasticity in terms of use and may need to be subdivided and renovated in the future. The design vision needs to take this possibility into consideration. Designs and infrastructure will impact future options, their associated renovation costs, and the extent of disruption to both animal care and research.

One of the specialized needs that is contrary to larger, high density AHR, is the need for very small holding environments, such as “cubicle” rooms that hold only one rack each. Cross-contamination control, specialized environmental controls, behavioral studies, and others, may benefit from small dedicated holding environments. These smaller holding environments can also serve as quarantine rooms, disease isolation rooms, and to support other veterinary requirements.

Factoring in Changeout
Eventually, regardless of the number of IVC within a room, the changeout process needs to be, and rarely is, given detailed consideration in design. When the census within an AHR exceeds a design capacity that has taken into consideration animal care efficiency, racks often must be relocated into an adjacent hallway to service cages. In others, heavy racks must be moved about to allow access for cage change and this increases the risk for accidents and injury. In yet others, the change station and the required supplemental equipment like clean cages and water bottles are moved down to the end of rows, and animal care technicians are required to carry cages up and back the aisle between racks to change cages. If the change hoods are in fixed positions, then all cages within the room must be brought to the station for change. This is time consuming, ergonomically costly, and inefficient. Yet, this is imposed on the operations unit potentially for the lifetime of the facility if that is the course the design takes. Beyond intensive animal care procedures, there are the needs to keep the AHR tidy, organized, and clean and these interventions may also create commotion to some extent within a room. Rooms may be swept and mopped as frequently as daily, and there often are more intensive sanitary procedures that are done on a periodic basis. A larger room, one with twelve racks, will be subjected to the disturbances associated with these procedures for a longer period of time than an AHR with four racks or the thoroughness with which the task is completed may be impacted.

An Ongoing Dialogue
This discussion is presented with the intention of stimulating continued thought and dialogue regarding the process of design of mouse animal holding rooms and how this can best serve the parties of interest. It is possible to take two floor plates exactly the same size, and by adding or removing walls and corridors, achieve many more cages in one as compared with the other. This may be an extreme example, but the fact remains, AHR dimensions will translate to greater or lesser cage densities with associated complexities for both facility and research staff. As we have shown, several variables are of prominent concern and these dismiss the notion that “cookie cutter,” one-size-fits-all designs will in all instances satisfy the needs of investigators, operations managers, veterinary staff, and institutional administration. Yet, together, an informed, deliberate decision that weighs and balances the needs of all, includes room use flexibility as a facet of the design, and allows for future adaptation to meet differing needs will meet or exceed the needs for the life of the facility.

Mike McGarry, PhD of MCG Consulting has over 35 years developing facilities and directing laboratory animal programs at Roswell Park Cancer Institute,Mayo Clinic Arizona, and Arizona State University. He also has done basic and pre clinical research in a variety of lab animal species reported in over 90 peer-reviewed publications. He can be reached at mike@docmcgconsulting.com.

Michael J. Huerkamp, DVM, DACLAM has 25 years postdoctoral experience in laboratory animal medicine. He is the director of the animal resources program at Emory University where he manages facilities comprising over 155,000 gsf and a staff of 78. He can be reached at mhuerka@dar.emory.edu.

Andrew “Andy” Pesek, Jr. BS, RLATG, CMAR has over 16 years of experience in Laboratory Animal working at Texas A&M University, University of Texas Health Science Center-Houston and The University of Texas M. D. Anderson Cancer Center. He can be reached at atpesek@mdanderson.org

Jerry Percifield has a Bachelor of Fine Arts degree in Architecture and a Masters of Architecture. He has been a licensed architect for 34 years and is currently a Principal at Lord Aeck Sargent. Jerry has published over a dozen articles and co-authored several chapters for ABSA. He can be reached at jpercifield@lasarchitect.com