Lee Thompson, director of biosafety and containment facilities at the University of Texas Medical Branch in Galveston, sees four main factors driving the search for research space that can be converted across various biosafety levels: anticipation of future high containment needs; maximum utilization of very expensive laboratory and animal spaces; increased opportunities for grant funding; and preparation for bioterrorism or emerging infectious disease emergencies.

For organizations with a definitive BSL-4 program, Thompson sees certain flexibilities that can be built in to address these drivers, and to allow them to accommodate a variety of programs and types of agents.

For organizations that don't require BSL-4 space, he also sees a range of options that facilitate reconfiguration of BSL-2, BSL-3, and BSL-3 Enhanced spaces. Although based on fairly standard design solutions, such concepts can even support upgrading / downgrading spaces across these biosafety levels with relative ease.

Flexibility Features for BSL-4 Space

For organizations with a defined BSL-4 program, the cost-effective solution is often to build new space to accommodate that program, rather than upgrading existing BSL-2 or BSL-3 space.

Such thinking drove decision-making for UTMB's new BSL-4 lab annex. Originally conceived as a level 4 laboratory to support the World Health Organization's Reference Center on Tropical Diseases, the facility was initially designed along conventional lines, with the ventilation system and directional airflows all according to prevailing standards.

However, coming to terms with the implications of limited resources, the team began looking at flexibility options to allow the space to accommodate other potential programmatic needs, including multiple, simultaneous research programs; new security requirements; product-related research; expanded lab capabilities; and expanded animal capabilities.

During this stage of re-thinking, the U.S. bioterrorism initiative was passed, adding impetus to the search for flexibility.

In the final design, the 12,000-gsf annex to UTMB's biocontainment research center will feature roughly 2,000 sf of usable high-containment research space, including roughly 900 sf of animal space. The project architect is B2HK/SmithCarter, a joint venture between Houston-based B2HK and the Canadian firm, Smith Carter, and building engineering is by ccrd partners; both firms are based in Houston.

By putting animal space in high-containment areas, institutions can increase funding opportunities for certain research programs when it comes to applying for grants and supporting funds, explains Thompson. Institutions without theappropriate research space would simply be ineligible.

The design solution consists of a laboratory half and an animal half, with each side having built-in capabilities to serve needs typical of the other with relatively minor reconfiguration. For instance, both sides of the facility have laboratory capabilities. The main lab incorporates ducted biosafety cabinets, while the animal room has the capability for these to be installed.

The procedure lab houses a ducted biosafety cabinet, and has the hardware necessary to install a downdraft necropsy table. It also serves as an anteroom for the main lab. For added flexibility, the team chose to upgrade the sizes of autoclaves, and to add penetrations for biosafety cabinets and an additional biosealed door in the body shower. In addition, the animal watering system is piped throughout the building, with backflow prevention, allowing the labs to function as laboratory animal rooms.

Now nearing completion, move-in to the facility is anticipated by October 2003. Total project cost is $15 million.

The key to the design's flexibility is a division of the ventilation system into two separate—independent but integrated—systems. This provides UTMB management a range of choices regarding the active configuration of lab and animal space.

The estimated cost impact of the decision is $600,000. This cost premium results mainly from the fact that the decision to split the ventilation systems was made relatively late in the design process; if included in the project from the outset, Thompson notes the added cost for this feature would have been minimal.

A corridor around the lab—which is pressure-negative to the rest of the building and pressure-positive to the high-containment lab—serves as both an air reference corridor around the laboratory, and as a buffer between the lab and the exterior wall.

"If you put the laboratory on an exterior wall, you have a lot of problems with maintaining the pressure because of wind velocities and other environmental factors. If you put a buffer corridor around that, you have better control," says Thompson.

Access to the space—including the buffer corridor—is restricted for security reasons, but an added advantage is that this minimizes the chance of lab workers being startled by pedestrian traffic, reducing the risk of accidents and injuries.

Flexibility in Larger BSL-4 Labs

Another approach to flexibility—one more suitable to a larger biocontainment lab—can be seen in UTMB's proposed high containment expansion project.

The design of this new UTMB project features labs along one side of the building and animal space along the other, with a central spine of support spaces (procedure labs, centrifuge facilities, and storage space). Biosealed doors along the central spine and between sections of lab and animal space allow the amount of animal space supporting any given lab to vary. The design can accommodate multiple, independent BSL-4 programs—each with its own support services and structures—but also has the capability of increasing the animal space for each program.

A buffer corridor around the perimeter permits a given animal room to be taken off-line, decontaminated, and reconfigured, without interrupting any of the other scientific activities in the laboratory. Additionally, any of the animal rooms can double as a fumigation chamber when unoccupied.

"This lets you minimize the number of fumigation chambers that you have in the facility," says Thompson. "You take that fumigation chamber and put it into usable laboratory space."

Concepts for Convertible for BSL-2 and BSL-3 Facilities

For organizations that rely on biosafety space, but don't definitively require BSL-4 space, flexibility remains an important facilities consideration. This is especially true for many biotech diagnostic and production companies, which often require space that can be adapted between level 2 and level 3 capabilities relatively easily. They also need biosafety space that can be made operational in a short period of time, and that is cost efficient to construct and operate. As with non-biosafety labs, the most common design approach to achieve these goals is typically a modular concept.

"The modular concepts that support this degree of flexibility can get you all the way up to the BSL-3-Enhanced category without going to the expense of a level 4 lab," says Thompson. "Taking a BSL-2 facility up to BSL-3 Enhanced is a lot more cost efficient than building a BSL-4 lab and using it for BSL-3."

As an example, Thompson points to suite-based designs that can achieve level 3 capabilities through barrier penetration and directional airflow. Individual HEPA filtration on supply air, together with the capability to put HEPA filtration on the exhaust, allows specific areas to operate at higher biosafety levels if required by the research programs in those areas.

Another flexible solution for convertible BSL-2/3 space employs change rooms with shower-out capabilities between different areas. This permits separation of work with pathogenic organisms from product development and testing, per FDA requirements. Diffuser capabilities for HEPA filtration on supply air can provide an added degree of flexibility.

Such level-3 facilities can be built relatively inexpensively—as little as $265/sf.

Another approach to flexibility employs cubicle boxes within individual labs. Each cubicle has its own ventilation system, with directional airflow and individual cubicle monitors. On this design, each lab effectively has its own anteroom for donning personal protective equipment. The anteroom can also be maintained pressure-negative to the cubicle working area to satisfy requirements for product protection.

Each cubicle has a biosafety cabinet, some of which are ducted. Each also has a central penetration for services. Thompson describes this as "almost a plug-and-play environment."

BSL-3 space incorporating cubicle boxes can typically cost $450/sf, and such facilities can be brought online relatively quickly.

Flexibility and Programmatic Commitment

Whatever the demands for flexibility in planning for future high containment needs, Thompson stresses the importance of getting commitment from policy / management people not only to build the facility, but also for the scientific support programs it will house.

He cites an example from a national animal disease laboratory, which was designed and built in anticipation of certain—but as yet undefined—future research needs.

Upon completion of the facility, policy and management people were surprised to learn that the researchers needed to bring the agents they would be working with into the lab in order to develop the diagnostic techniques for those agents. In other words, they had to risk exposure in order to learn how to detect it. The resulting confusion caused significant delays for commissioning the facility.

"If you are going to have a level 4, you have to meet with the administration and with your scientific groups, and get a commitment, not only for the facility, but also for the scientific support programs. Otherwise it is not going to work," says Thompson.

By John Treat