However, constructing even a small scale BSL-3 or BSL-3Ag project can be a difficult undertaking. The biggest challenge is overcoming the cost inefficiencies inherent in a small-scale project. The small scale requires a higher unit cost to construct, and typically, there is no reduction in design and engineering fees. The fee structure remains the same because whether a BSL-3 lab is a 1,000-nsf renovation or a 10,000-nsf part of new construction, the design still requires one of everything in order to meet the biosafety requirements as outlined in the Biosafety in Microbiological and Biomedical Laboratories manual.

"Small biocontainment facilities for work with most agents can be safely developed, monitored, and operated based on the science of biosafety and the tools that have been developed over the past 50 years," opines Jon Crane, principal with CUH2A Inc. in Princeton, N.J. "The greater challenge exists from the larger multi-agent, multi-user facilities that require a sophisticated facility design and a knowledgeable biosafety staff actively managing biosafety in the facility."

Nonetheless, three potential problems loom on the horizon: the shortage of qualified design firms and contractors, proper maintenance of BSL facilities, and a shortage of trained personnel.

Qualified Consultants

First, few contractors and designers have the experience to properly design biocontainment facilities, and the few who do are not geared up to handle the hundreds of small (1,000 to 5,000 nsf) space conversions and upgrades that will be happening all over the country to create small, imbedded biocontainment suites.

"Finding qualified contractors to build these facilities can be especially difficult," says Jeff Schantz, principal with Lord, Aeck & Sargent Architects in Atlanta. "Outside of a handful of contractors, there are very few who have constructed a high containment lab. It is important to team your contractor with an experienced design or facilities professional who can guide the uninitiated through the process. The contractors who have the most experience with these types of facilities are ones who've worked for government, university, or pharmaceutical clients.'

Lou Welker, chief of the Facilities Engineering Branch of the U.S. Department of Agriculture concurs, "Often finding a contractor who has an understanding of how a biocontainment facility needs to be commissioned and tested can be a monumental and frustrating task."

Equally important to issues of design experience is the experience of the owners. Key staff with biocontainment knowledge must be present and active in the planning process. Personnel who are responsible for compliance policy, those who will operate and maintain the facility, and those with responsibility for safety and health should be involved very early in the process and continue to participate throughout the life of the biocontainment project.

"Selection of design firms by owners of biocontainment facilities under development can be based on incorrect assumptions of a firm's experience," says Scott Rusk, biocontainment specialist with Flad & Associates in Madison, Wis. "Smaller projects do not always draw interest from firms with the appropriate experience. That, combined with the possible inexperience of the owner in operating and managing these types of facilities, can cause delays, wrong solutions, excessive protocols and management effort, high costs (both construction and operation), and risks to future science programs and funding opportunities."

Each biocontainment facility is unique in that it needs to be designed to accommodate the specific planned / envisioned science programs. Good design follows a strong understanding of the intended science and projected use of the facility. Design firms need to have knowledge of the science programs, the day-to-day operational issues, and the applicable regulatory requirements. They should also have an understanding of the issues revolving around the administration and management of biocontainment facilities in order to assist owners in developing their facilities.

"Addressing the CDC's Select Agent requirements adds a new wrinkle to an already complex issue," says Welker.

The results of working with an inexperienced firm are likely to be two-fold: schools will end up overpaying for features and systems they don't need, and the facilities will not, in the end, be safe or even usable. Unfortunately, it isn't until the final day of testing that a facility is discovered to be unusable, at which point walls have to be torn out to re-seal utility lines and boxes, etc. Biocontainment buildings must be designed and built by people who have enough knowledge of the issues to ask the right questions.

Low-cost and inadequate systems, materials, or layout can result in short-term solutions but can compromise flexibility and building longevity. However, there is also the risk of spending too much based on lack of knowledge or understanding of multiple solutions or requirements, resulting in the acceptance of inadequate facilities. There must be a balance to the process to avoid both ends of the spectrum. Safety is at risk if shortcuts or critical elements are missed due to lack of knowledge or experience.

There are a number of options that may help to reduce the cost of acquiring BSL-3 space. Jeff Schantz has these suggestions:

Roll it into a new project. This approach is the easiest way to construct BSL-3 space that is cost effective and will attract the type of professional talent (scientists, architects, engineers, and contractors) experienced enough to build it. It will also blunt the cost of HVAC systems, as much of the required system capacity (supply side especially) can be piggy-backed off other systems.

Gut renovation of a top floor space. The next best option is to do a gut renovation, preferably right below the roof. This will allow direct access to roof-top placement of exhaust air components, and if a new supply air unit is required, it will be close by, saving costs by reducing duct runs. It also helps to have a floor below to deal with plumbing issues. If the lab is to be slab on grade, consider using under-sink carboys to collect liquid waste that can be autoclaved out as opposed to liquid decontamination systems.

Convert existing non-BSL lab space to BSL-3. This can be very tricky, especially if the room does not have properly sealed surfaces, access to an autoclave, proper HVAC systems, or entry vestibules. There is also the issue of air systems to consider. It is important to understand that existing fume hood ductwork may not be useful as exhaust for Class II/Type 3 cabinets. It may not be sealed or tested for leaks.

Convert animal space to BSL-3. Most animal facilities that meet AAALAC/USDA standards will have 80 percent of what it takes to create BSL-3 space. Animal facilities typically have sealed and coved surfaces, adequate supply and exhaust air, and service paradigms that can support high containment. This strategy works particularly well if the proposed facility is going to be doing in-vivo work at ABSL-3, or is harvesting tissue or cell samples from nearby animal colonies.

Use modular space. There are many situations where a modular BSL-3 can be an appropriate solution. However, the choice of a modular solution should not be driven by cost, as BSL-3 modular labs can cost as much as building new space or renovating. Modular solutions are most appropriate in the following situations:

Proper Maintenance

The second looming problem is the proper maintenance of biocontainment facilities. Such maintenance is very complex, expensive, and human-resource intensive. Employee illness, poor scientific results, the loss of research time and dollars, and losing the ability to continue research are all consequences of improperly maintained BSL facilities.

Maintaining biocontainment facilities is an integral component to facility design. Many decisions made during the design stage have long-term implications for maintenance and "too often good maintenance elements and techniques are 'designed out' during the design stage to reduce construction costs," says USDA's Welker.

"The involvement of many disciplines—owners, users, compliance/safety officers, and designers—during the planning and design of facilities helps to ensure the full scope of costs and complexities are well understood and that the facility can be operated as intended," says Flad's Rusk.

Tony Della-Porta, managing director with Biosecurity and Biocontainment International Consultants in Australia, addresses other maintenance concerns: aerosol containment, HEPA filtration, and fumigation.

Aerosol containment, and its re-entrainment into buildings, is one of the reasons why BSL-3 laboratories operate under negative air pressure, and why air exhaust needs to be HEPA-filtered. When laboratories rely on the containment provided by HEPA filters in biological safety cabinets, any accident outside the cabinet cannot be properly contained.

"It is of concern to me that some countries do not have proper standards for the operation of BSL-3 laboratories, and that they do not require HEPA filtration of the air exhaust," he says.

Also, if BSL-3 laboratories are not sufficiently air tight, fumigation is a potential hazard to people outside of the laboratory. Laboratories need to be constructed so that they meet a pressure-decay standard, rather than require an ongoing search for leaks when under negative pressure.

"I know of a number of incidents of gassing with formaldehyde, fortunately with no fatalities (yet)," says Della-Porta.

Properly Trained Staff

The third looming problem is the need for adequate training of users and maintenance technicians in addition to quality design and construction. Exposures to scientific staff and subsequent illnesses often occur as a result of breaks in protocol, which underlines the requirement that infectious disease research with highly pathogenic agents needs to be done by people who are extensively hands-on trained in biosafety protocols.

Della-Porta has been involved with several investigations of laboratory accidents around the world. He concludes that a major problem in all of the incidents he has investigated has been the poor training of staff and improper operating procedures, rather than accidents associated with containment. There appears to be a need for laboratory accreditation and proper staff training.

"In virtually all of the laboratories we investigated, there was little understanding of infection control and how to handle laboratory spills," he says. "This becomes of greater concern as molecular biologists move into BSL-3 and 4 laboratories with little microbiology training."

"Even the most perfect building needs to have people with proper training, knowledge, and experience working within the facility in order for it to function appropriately and help to assist the scientific discovery process," says Rusk.

Training requires time, and it is an important point to note that there is a general shortage of trained people, as well as a lack of good training courses. This applies to the bench as well as the people responsible for managing, operating, and maintaining the facilities. The lack of trained biosafety personnel is being driven by the pace at which new BSL facilities are being added. Many institutions that previously were not in the biocontainment business now are.

Recently, a number of institutions have begun offering post-professional training to fill the needs of a growing demand for biosafety workers. Much of this demand is being driven by the lack of foreign scientists who have traditionally been attracted to the United States. However, the only currently existing course in North America that actually trains staff hands-on in public health issues concerning select agents and emerging diseases is at the Canadian Science Centre for Human and Animal Health.

The issue also attracted the interest of the U.S. Congress, which held a hearing on February 25, 2004. It recognizes the United States historical dependence on attracting the best scientific talent from around the world as a key factor in its preeminence in science and development.

"Much of this sounds quite ominous if the situation continues to develop on its present course," says Schantz of Lord, Aeck & Sargent. "It is clear that until the world political and security situation improves, American science will have to find ways of coping. Unless we are willing to invest, recruit, retain, and reward work in the sciences to attract the highest quality domestic workforce available, we will still have to consider our science community part of the world community, and in need of foreign talent."

In Summary

Unfortunately, there is not one single solution to the issues outlined above. As potential owners realize their opportunities and as facility planners, programmers, and designers become engaged in helping develop biocontainment facilities (large or small scale), it is highly effective to integrate all components (management, operations, science programs, design, the public, engineering systems, security, safety, maintenance, funding, etc.) to successfully and properly carry out these projects.

"My caution to owners is to be aware of what you are buying since not all biocontainment facilities are created equal," says USDA's Welker. "There are not enough people—consultants and contractors—around who have done this and know what they are doing. Facilities are being built, and money wasted, to achieve an operating level, such as BSL-3, that is not needed."

Scientists also need to be careful not to over react and classify organisms at too high a biosafety level. Laboratory staff, from the laboratory directors on down, need to take responsibility for the biosafety within their facilities and ensure that staff are properly trained and that their facilities meet present containment requirements.

CUH2A's Crane, who has designed more than 50 BSL-3 and BSL-4 labs, advises, "Low-cost, appropriately designed facilities can accommodate much of the science required for BSL-3 work, and are easier and less costly to design, operate, maintain, and modify. Be sure to understand the reasons behind the choices made when adding features to a biocontainment facility."

by Steve Westfall with contributions from:
Jon Crane, Principal, CUH2A Inc.
Tony Della-Porta, Managing Director, Biosecurity and Biocontainment International Consultants
Scott Rusk, Biocontainment Specialist, Flad & Associates
Jeff Schantz, Principal, Lord, Aeck & Sargent Architects
Lou Welker, Chief, Facilities Engineering Branch, U.S. Department of Agriculture