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Operating a BSL-4 Laboratory in a University Setting

Center was approximately $1 million, not including the daily maintenance costs of the hot lab. Both laboratories had to be operated concurrently in or- der to preserve the integrity of the testing until Hil- liard’s team determined that the new Center could function efficiently on its own.

The architectural firm of Lord, Aeck and Sar- gent designed the first phase of the Center, while construction of the BSL-4 lab was supervised by the architectural firm of HOK in cooperation with The Baker Co., which customized the 32-linear-foot glovebox cabinet.

tigators. The BSL-3 and -4 laboratories have a mag- netic card access so that entry and exit into the facili- ties can be tracked by a computer. With the addi- tional restrictions imposed by the new Homeland Security Program, all individuals who work within the BSL-3 and -4 labs must first have federal security clearance after submission of extensive documenta- tion to the FBI. The facilities must also meet Clini- cal Laboratory Improvement Amendments and Se- lect Agent inspection requirements to carry out the research and diagnostic missions of the laboratory.

Designing a BSL-4 Laboratory

Key Components of a Maximum- Containment Facility

The Viral Immunology Center, housed in the University’s six-floor, 500,000-sf natural sciences building, features a departmental animal facility in the basement and BSL-3 and -4 laboratories on the third floor, including a specialized BSL-4 for small animal models of disease. The Center, which occu- pies about 5,000 sf and employs 30 people, also in- cludes two support BSL-2 laboratories, a biochemis- try lab, robotics facility, offices, a fermentation lab, and shared departmental resources, including elec- tron and confocal microscopy areas, a sequencing core, and a FACS-analysis core for cell sorting.

The activities that take place in the Natural Sci- ence Center are of particular interest when design- ing a BSL-4 laboratory in a university setting. This building typically houses the departments of biology, chemistry, biochemistry, physics, and anatomy in addition to the BSL-4 lab. Research activities that are not part of the viral laboratories must also be taken into consideration when deciding where to locate the BSL-4 suites. Other activities to consider include teaching sessions and seminars.

Providing access to the laboratories in a manner that protects visitors is critical to the efficient opera- tion of the facility. Serious consideration is given to the type of barriers that are erected between com- mon access hallways and restricted areas to ensure that lay visitors and research supporters can view the work taking place without being exposed to poten- tial risks. Access is provided via keypad entry for stu- dents, faculty from other disciplines, visiting scien- tists, security and maintenance personnel, and inves-

Each day Hilliard’s facility receives up to 20 boxes from all over the world from individuals who may have been exposed to the secretions of a Macaca monkey. Minimizing the transport of materials going to high-containment areas is critical. When the sam- ples arrive, they are triaged to determine what tests must be done so the results can be sent to the con- cerned individuals as quickly as possible.

The packages, transported through an isolated hallway that is sectioned off from other areas of the facility, are opened in the Level 2 unpackaging room, attached to the BSL-3 and -4 suites. Each of these areas can be accessed only by computer- controlled keypad entry. Any materials that leave the BSL-4 facility undergo an intensive search for evi- dence of any live virus, using virus plaque assays to verify that all virus has been inactivated. If the assay is negative, the chain of custody for removal begins.

Items that leave the BSL-4 laboratory must go through two sets of autoclaves or two sets of cross- linked glutaraldehyde dunk baths. Dunk baths en- able chemical sterilization of the outside wall of sub- mersed containers. This allows a live virus to be re- moved from the cabinet for ultra-low freezing and storage within the BSL-4 and passage of inactivated materials to the Level 2 labs. Live virus never leave the suite.

The disposal system consists of two redundant 150-gallon tanks that are released into a boiler- decontamination unit. A chilling mechanism cools the water, which is released into the public system


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