The biological safety officer is responsible for tracking every aspect of science in the facility, including the incoming and outgoing materials, personnel, and animals to ensure that movement between various biocontainment levels can occur seamlessly with the proper protocols and procedures to minimize accidental exposure to harmful pathogens.

“It is important to have an integrated building where safety is combined with facility design, standards of practice, and the necessary scientific equipment to provide a safe and productive research environment,” says Robert DeGenova, an associate principal at Hillier Architecture in Princeton, N.J. “There is a lot of fact-finding and preparation required to design these very complex facilities and it starts with understanding the type of research that will be conducted in the building.”

Architectural Design Considerations

The most suitable design for aerosolization facilities can be planned only after a thorough risk assessment is performed. A detailed analysis is necessary to determine the type of Select Agents that will be handled in the facility, the level of risk, and the size and species of animals to be housed in the building. The answers to these questions will be used to determine the procedures and protocols that must be implemented to ensure safety and emergency preparedness for all potential hazards. The hazards are evaluated based on the likelihood that a problem may occur and the consequences that would result.

Designing multi-pathogen facilities that house multiple species requires the use of specific protocols for different animals and the type of research being conducted. Documented SOPs reduce the potential for exposure to humans, animals, and  the environment, while preventing cross-contamination between the different kinds of research taking place in the building. Detailed requirements must be outlined to ensure that all individuals working in the facility understand the importance of safety procedures, operational standards, personal protective equipment, and engineering protocols.

“We want scientific results that are reliable because the proper protocols are in place,” says DeGenova. “Where possible, we rely upon proven experience. We are pleased that the research community is open and collaborative so we can learn from each other’s successes and failures.”

Being prepared to safely handle multiple pathogens and to effectively deal with emergencies can be achieved by preparing a detailed checklist defining the following:

• agents (form, concentrations, and expected manipulations),
• animal models,
• expected toxic chemicals and/or radiation use,
• people, materials, and animal flow issues, including the transport of hazardous materials into the facility and hazardous waste out of the facility,
• potential risks, threats, probabilities, and consequences,
• required engineering controls, and
• special ventilation, plumbing, and electrical needs.

Adhering to the highest safety standards is especially important when working in BSL-3 facilities because exposure can lead to illness or death, treatments for exposure to certain pathogens are limited, and there is the potential for the disease to spread by splash, spray, or aerosol accidents. Measures must be taken to prevent employee exposure and the release of any aerosol within or outside the facility.

“There has been an explosion of understanding of what constitutes BSL-3. In response to emerging needs and health risks, BSL-3 has become the big box for a lot of pathogens,” says DeGenova. “The threat of diseases, such as Mad Cow Disease, is worldwide. Tuberculosis is also re-emerging and older drug therapies may not be effective.”

Equipment Solutions

Most of the new biocontainment laboratories have dedicated lab space to perform aerosolization research, working with a range of animals from mice to non-human primates. Safe and effective ways to address the hazards associated with the aerosolization of animals have been developed.

Taking certain steps before selecting equipment ensures the successful operation of a high-containment aerosolization facility.

“The first thing we tell our people is to get input from the end users to determine their needs,” advises Mark Zarembo, the custom products division manager at the Baker Co. in Sanford, Maine. “They may need something special located in the glovebox and they need different configurations depending on the type of research they are doing. Any of the manufacturers selected for Class III equipment will need to know these things at the beginning of the project.”

Building an integrated facility can be done much more smoothly when input is also obtained from biosafety officers, the architects, the HVAC engineers, maintenance people, and those who will be handling the animals. Talking to other researchers who have used aerosolization equipment in the past is a good idea to determine what works well and what does not. Gathering the necessary information will ensure the building is equipped with the best solutions and offers the maximum operating efficiency and highest level of safety.

Be sure to consider what will be located in the space around the equipment and whether the HVAC capabilities are sufficient. Decontamination protocols should be in place for each piece of equipment. Since much of the equipment consists of large, gas-tight structures, it is essential to ensure the units can be moved from the loading docks into the laboratory without being compromised.

“We have had cases where the equipment had to be hauled up to the eighth floor through an elevator shaft, so be careful about the selection,” says Zarembo. “Consider the path and the way to get the equipment into the building. You also have to consider equipment lead time and the reality of when the equipment will be available to researchers.”

Once equipment is installed, it must be certified prior to use and this is typically done by a qualified, independent third party. Testing should include the HEPA filter leak test, which requires special instrumentation, special knowledge, and special procedures. HVAC balance must be tested to ensure proper pressurization and to verify that alarms are operating properly. All ancillary equipment should be checked to guarantee top operating performance.

Mechanical, Electrical, and Plumbing Considerations

There are numerous functional and technical criteria that must be met as part of the HVAC design requirements for the aerosolization suites, according to Allan Ames, a principal at Bard, Rao + Athanas Consulting Engineers in Watertown, Mass. The suite is typically divided into three or four zones (anteroom, holding room, and aerosol challenge room) with an HVAC system capable of providing 15 to 20 air changes per hour. The supply is 100 percent outside air with 100 percent exhaust. The AHU and exhaust fans require redundant units to ensure that there is no unintentional shutdown during operation. A Class III device like the glovebox requires two HEPA filters in series per NIH standards. One filter is located on the glovebox and the other is typically located remotely, possibly in the interstitial space, so maintenance personnel can access it using proper protocols.

Animal holding rooms contain microisolator racks with direct exhaust and thimble connections. Each room in the aerosolization suite is a pressurization zone with interlocking doors and electronic pressurization monitoring systems. All exhaust ductwork serving the suite is welded stainless steel. A general exhaust outlet in the ceiling is required to help ventilate the aerosol challenge room and holding rooms.

The Class III glovebox has a low-volume (200 CFM), high-static exhaust connection. This can be mitigated by having the glovebox manufacturer supply an integral booster fan with the equipment. These would be run in series with the main exhaust fans. Two low-flow, high-static exhaust fans (one primary and one standby) in parallel located in the interstitial are required per NIH standards to exhaust the glovebox to atmosphere.

The design of the BSL-3 rooms includes constant volume supply and exhaust with hot water reheat valves, proof of proper air pressure and temperature at each room, individual exhaust connections to each rack, supply HEPA filters at each cage rack, a decontamination sequence, and special software programs for data collection, alarm management, and alarm notification.

Air flow is important when considering the necessary decontamination sequence. At the Duke University Global Health Research Building there is a wall separating the Class II glovebox with a BSL-2 biological safety cabinet in the passthrough into the Class III glovebox. Generally, the air flows from the corridor into the anteroom, into the holding room, and then into the aerosolization suite.

It is important to understand the efficacy and risks associated with decontaminating one room versus all of the rooms at the same time in order to develop decontamination protocols. Can each room be safely isolated and decontaminated without the decontamination gasses entering the adjacent rooms? The design must consider the location of bubble-tight dampers, whether redundant HEPA filters are needed, and budgetary concerns.

The gloveboxes at Duke have a separate exhaust going to a filter containment box and then the individual rooms have separate exhausts from the biosafety cabinets and holding cubicles. On the supply side, each room is separated with the anteroom and the autoclave having their own supply zone.

Ductwork in aerosolization facilities is very dense and is typically located in an interstitial space. Abundant mechanical space is necessary to provide service personnel with ample room to repair and maintain the equipment. Hard ceilings with no access panels are a good choice to prevent contamination, so alternative access to the piping and ductwork is necessary.

“You have to think about all of the failure scenarios and decontamination scenarios and make sure the sequences are built into the control system,” says Ames. “We had quite a bit of discussion about that with the maintenance people. Everyone must work together to design the safest, most technologically sophisticated, and effective environment to achieve the desired outcome.”

By Tracy Carbasho

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