“When you introduce animals into the laboratory containment boundary, it definitely gets more complicated,” says Lauri Kempfer, lab planner with Flad Architects. “You have a host of different users, protocols, and process flows, which essentially amount to two distinct management and operational protocols and design characteristics that you wouldn’t otherwise have in just a laboratory setting. Animal care specialists, as well as laboratory researchers, will be working in the same environment. Therefore under whose protocols will the space be managed: veterinary care or the research lab? In addition, design characteristics, as well as animal procedures and laboratory research practices, will need to cohabitate in the same space including waste flows, feed handling, and bedding.”

Due to stringent design parameters and safety protocols, high-containment environments are extremely expensive to build and operate. It is crucial to have a thorough understanding of protocols and process flows before designing an integrated facility. This understanding is fundamental to efficient facility organization and encompasses such considerations as pathogen classification, species type and quantity, animal housing, safety protocols, regulatory compliance, and security, as well as the ever-important cost of the facility.

The Business Plan

Central to the process of designing an integrated high-containment animal facility is the business plan, which should outline research objectives, processes, protocols, and potential outcomes, and incorporate the estimated cost to operate the facility. The costs should include research, health and safety, maintenance and engineering, and also address local community perceptions and concerns. All too often design and engineering solutions are required following public review. These are usually unexpected and can be costly from both a capital as well as operating cost perspective. For example, disinfection systems that are not required at a Level 3, may still be requested by local municipalities.

In general, animal operations are much easier to integrate into the discovery phase of a research effort than into later development stages. Typically, toxicology programs involve large numbers of animals and lengthy durations, versus discovery studies that include fewer animals and shorter studies, says Steve Freson, principal and facility planner with Flad Architects.

“Integrating large toxicology study programs into a laboratory environment is impractical due to the length of the studies,” says Freson. “You’re much more likely to see integrated animal facilities on the discovery side or for specialized operations than on the later stages of any kind of product or therapeutic development phase.”

The increase in the volume of operations is a key consideration when moving into high containment facilities. For example, a 50 percent increase over a normal BSL-2 to accommodate 24/7 operations in a BSL-3 would not be unusual in the first year of operation. The corresponding increase in steam capacity to run multiple autoclaves for decontamination and cagewash systems would in turn require multiple boiler arrangements to maintain the necessary peak demand load. The operating model would thus need to include the appropriate number of engineering operators to maintain these systems.

Facility Organization

The integrated laboratory facility should be organized to facilitate anticipated process flows and protocols. Basic strategies include organizing by department, biocontainment level, pathogen under study, or animal type.

Animal size is a major factor in containment planning. For example, ventilated caging is sufficient to provide primary containment for rodents infected with a BSL-3 aerosolized pathogen. However, non-human primates (NHP) infected with the same pathogen can be housed in primary containment caging systems similar to bio bubbles or Class III cabinets, or housed in rooms designed under either a BSL-3Ag or BSL-4 design parameter. The two choices provide two very significant operating and capital cost scenarios. The expertise and numbers of animal care staff will be quite different for the two species as well, as will equipment requirements and design parameters.

Location of high-containment support services such as decontamination is another key consideration, as is the organization of utilities. Of particular importance in the organization of biocontainment environments is the desire to stack MEP components. BSL3-Ag environments, for example, ideally place HEPA filtration and air supply and exhaust systems above the containment area, and effluent decontamination systems below.

“The basement level, occupied floor level, interstitial level, and exhaust platform should be efficiently designed as an integrated system,” says Freson, “rather than providing systems that require long horizontal runs. The stacked design provides ease of maintenance and accessibility and prevents the build up of contaminated particles in the ductwork over non-contained spaces.”

“Direct vertical drops and gravity flow are ideal designs with respect to risk, biosecurity, cost, and efficiency,” says Kempfer. “Your level of risk increases when you need to route your contaminated air to another location in the building. In addition, slab-on-grade installations require double-wall and leak-detection systems, an additional cost issue.”

The diversity of pathogens intended for study in the facility directly impacts organization.

“You need to consider whether you want to build a hierarchy of spaces in the facility,” says Freson. “Is the facility designed to become a single pathogen or multiple pathogen facility, or to be designed by function or funding program? These organizational structures will limit the flexibility of the facility over time.”

Building Systems and Infrastructure

Mechanical, electrical, and plumbing considerations are much more involved in integrated animal biocontainment facilities.

“The facility must be sealed construction to different degrees depending on the biosafety level,” says Kempfer. “Electrical conduits and all penetration points need to be in the right place as second chances in BSL-3Ag concrete systems are not negotiable. Biowaste piping is completely dedicated in these facilities, and some biosafety levels require effluent decontamination.”

The square footage devoted to mechanical systems in these facilities tends to be at least as large as the amount devoted to programmed areas such as labs and vivaria, and associated support spaces. Biological containment guidelines help to assess the level of risk associated with the agent and the type of research conducted, and that risk directly correlates to the amount of redundancy required for mechanical systems. This is what accounts for the increased square footage, says Kempfer.

“You can typically use one air handler for an officing facility or low-containment lab, but when you get into higher containment you need to dedicate those air handlers, as well as provide redundancy. BSL-2 spaces can’t share BSL-3 air. BSL-3 spaces can’t share BSL-3Ag air.”

Air filtration and treatment add yet more complexity.

“Higher containment levels require HEPA filtration,” says Kempfer. “BSL-3 or higher requires HEPA filtration of exhaust air. BSL-3Ag requires HEPA filtration for both exhaust air and supply air, and then redundant HEPA filtration on that exhaust air, and then one more redundant HEPA filtration before that air can be exhausted out of the facility. Plus, you need to supply one of those for each room, independently.”

Security

After September 11, 2001, government regulations for Select Agent research intensified, requiring federal clearances for all personnel working near and directly with Select Agents. Determining who should have access to which areas is a major design consideration.

“For example, you have an integrated facility that has some laboratory functions within it, some animal holding rooms, maybe a procedural space, and some support functions,” says Kempfer. “For registration purposes, you need to evaluate which individuals require access to that facility and where Select Agents are stored. There is a balance that needs to occur between the functions you require in that facility and the personnel you want to have access.”

Security solutions include performing an initial threat and risk assessment; employing multiple layers of security mechanisms, including exterior perimeter security, high-security keys, proximity readers, and bioscript readers; and implementing safeguards such as bulletproof glass, glass-break detection devices, laser detection devices, and blast protection. Seismic loads as well as potential loads of wind and snow must also be considered.

Risk

Overall, it’s important to discern the level of risk the client is comfortable with, says Freson.

“Sometimes, it is far more important for researchers to evaluate how many levels of personal protective equipment or how many showers they are required to take to get from zone to zone,” Freson says.

“In academia, when researchers indicate, ‘I want an integrated facility,’ what they’re really asking is, ‘Can I have my animal holding room next to my lab because it’s efficient and because I don’t want to have to go through all the veterinary protocols,’” he continues. “In contrast, the pharmaceutical company testing clinical or Phase II or III-grade product will say, ‘We are required to separate these areas because we can’t afford the potential for cross-contamination compromising all of our expensive pharmaceutical work.’ Integration is complex and requires careful planning and an understanding of the design protocols and the owners’ operating cost parameters.”

By Deborah Kreuze