“Due to the hierarchy of systems in a facility of this type, there are a number of key issues regarding integration that need to be considered. These issues can impact capital costs as well as long-term operating costs, both for building and operations,” he continues.

Some of these issues include:
• Facility organization function
• Single versus multiple pathogen research
• Specie type and separation
• Research function
• Route of transmission
• Operational approach

Another common concern that exists in an integrated facility is whose protocols control the space—veterinary or laboratory. Freson recommends using both protocols.

“Typically the protocols are not that restrictive to mandate one over the other; recognizing that, if challenged from outside, you will need to address both concerns.”

“Minimizing multiple containment zones is beneficial,” says Lauri Kempfer, vivarium and laboratory planner with Flad Architects. “Recognize that the rule of thumb is to design as simple and as small a containment zone as possible. Maintaining multiple zones provides some flexibility in operations, but can add significant costs.”

These options, however, are difficult to apply to a BSL-4 facility. Typically, BSL-4 facilities are integrated, where laboratory and vivarium research occurs within the Level 4 containment barrier. The risk of a potential accident is higher and access should be strictly controlled to only suite-certified individuals.

Case Study A

This Regional Biocontainment Laboratory (RBL) houses approximately 25,000 to 30,000 rodents utilizing ventilated cages. The facility is designed to test several different pathogens utilizing an aerosolized form of the pathogen.

The process of administering the agent is extremely tedious, involving the transfer of the rodents to a nose-only delivery carousel and back to the cage. All of the activities are performed in a Class III cabinet. It is anticipated that activities will limit technician throughput due to the confines of a Class III cabinet. Therefore, the facility has to be designed to accommodate the high personnel volume of multiple shifts.

Under full operation, the cage turnover rate would be very high, as the rodents would be expressing symptoms approximately every seven to 10 days. The design anticipates that the high cage turnover rate would need a significant operating staff. This was one of the driving factors for a stand-alone function, limiting staff entering and working in the facility, and lowering risk.

Case Study B

This expansion of an existing BSL-3 facility, designed for a contract service provider studying multiple BSL-3 human pathogens in nonhuman primates (NHPs), exhibits a high level of integration. All of the BSL-3 activities are inside the BSL-3 perimeter, including the laboratory operations, procedure room, holding, and all decontamination operations. All personnel enter the facility through a central locker facility. Animal handlers pass through an additional gowning area to enter holding rooms. Other containment measures include an effluent decontamination system, room-by-room vaporized hydrogen peroxide, and individual room HEPA filtration.

NHPs are anesthetized in the holding room, transferred to a primary-containment biosafety cabinet, and wheeled down a common BSL-3 corridor to the aerosolation laboratory, where the cabinet is docked to a Class III cabinet via alpha-beta ports. After dosing and challenge, the animal is returned to the holding room.

“Although the animal leaves its room, it never leaves the containment environment,” says Freson.

The client is doing a high volume of contract work and employs cross-trained workers who perform a range of tasks, resulting in a highly cost-effective operation. The facility was designed as compactly as possible to facilitate efficient process flows and minimize operating costs, thus maximizing value to clients.

Case Study C

This facility, currently in planning stages, is a multiple-pathogen, multiple-species BSL-3Ag academic research facility for agricultural pathogens. It includes a greenhouse facility and an insectary, and operates separate containment programs for plant pathogens and animal pathogens. Since the insect vectors under study are capable of infecting both plants and animals, a clear physical separation of research efforts was desired to avoid cross contamination. However, the university also wanted to keep all of its high-containment agricultural research programs under one roof, creating program continuity.

“Integrating a BSL-3Ag environment is particularly challenging because of the space requirements for large-animal handling, such as animal movement systems, necropsy facilities, squeeze chutes, and other devices to hold animals for procedures such as blood draws,” says Freson. “These environments typically devote only about 15 percent of net assignable area to animal holding areas, with the remainder dedicated to access areas around the perimeter of holding areas, gown-in-gown-out processes, and animal care functions such as cleaning and storage of feed and bedding materials.”

In addition, mechanical, electrical, and plumbing require significant space for redundant USDA 242 requirements, including pressure decaying.

Since research efforts encompass multiple pathogens, a “hotel” suite design approach was utilized, allowing any individual holding room to be devoted to any pathogen type and any animal species. Shower-out processes are incorporated into entering and exiting protocols. A long, linear link design with multiple airlocks between functions achieves the necessary separations while minimizing the layers of protocols that could impair the facility’s smooth operation.

Case Study D

Multiple factors influenced the integration of another academic research facility studying Select-Agent, highly pathogenic avian influenza in multiple species, including rodents, ferrets, fowl, and nonhuman primates. The Select-Agent status, as designated by USDA APHIS, required BSL-3Ag pressure-decayed facility design. Adding the BSL-3Ag component to this leased facility—a 1980s-era building originally designed for office use—required an entirely new addition be constructed to achieve pressure decay and the vertical stacking of mechanical, laboratory, and animal housing systems that is required for BSL-3Ag containment.

Since only one pathogen will be under study, multiple species can be housed within the BSL-3Ag containment without concern for cross-contamination.

“BSL-3Ag space is high-dollar real estate,” says Kempfer. “You want to prioritize what goes into the space.”

The high cost of BSL-3Ag space made it more cost-effective to house rodents in primary-containment caging outside the BSL-3Ag area, reserving that space for ferrets, fowl, and nonhuman primates.

Locating gown-in/gown-out locker rooms at the perimeters of BSL-3Ag and BSL-3E environments as well as autoclaving at entry and exit points allows animal-care workers and other researchers to circulate freely outside these areas and reduces the number of security clearances needed for the operation. The BSL-3Ag facility is fully integrated, incorporating procedural, necropsy, and laboratory spaces to enable researchers to conduct a full spectrum of animal research functions without having to go through the cumbersome process of donning and shedding personal protective equipment and transporting potentially agent-infected waste in and out for certain research steps.

Although the design fulfilled the requirements of the international building code, further modification was necessary to accommodate fire department access and life-rescue functions. Locations of security access control checkpoints were altered and hardware types modified to enable limited access for the fire department.

Case Study E

This multistory research facility of a major pharmaceutical company houses animal operations on multiple floors. Although the facility is not a biocontainment facility, workers “gown in” at each floor level for biosafety purposes, just as they would in a containment operation, to avoid cross-contamination. Since the environment is not strictly a biocontainment environment, it was feasible to transport animals and materials via elevators from a lower-level vivarium to locations throughout the three-story facility.

“In a contained environment, the elevators’ piston-like action could draw infectious material between levels,” Freson says, “which would simply not be acceptable.”

Integration, in this case, is on a floor-by-floor basis directly connected to a research laboratory as opposed to separate, functional areas.

By Deborah Kreuze