“Despite going through the commissioning process, many biocontainment laboratories do not meet either the engineering or operational guidelines required to ensure containment,” says Dr. John Keene, WorldBioHazTec Principal.

Due to the number of contractors, vendors, and facility personnel involved in creating a biocontainment lab, deficiencies in areas critical to meeting regulatory requirements can be overlooked. These issues can be successfully identified and resolved by conducting a third-party certification review of the facility. WBHT is an independent consulting firm that works with various global entities to certify facility compliance with CDC, NIH, USDA, and WHO requirements, as well as country-specific regulations. As part of the process, a team of biosafety experts including engineers and operational specialists conduct a detailed audit of the facility’s design, construction, and operating procedures, then submits an assessment with suggested measures for resolving any deficiencies.

“Given the expense and risks of operating biocontainment facilities, it is essential to get an objective review from a professional standpoint,” says Keene.

United States Guidelines and regulation, and the WHO biosafety manual, define laboratory containment in two areas: facility design and operating procedures.

“We can overcome some lapses in engineering by adjusting the procedures that are done within the facility. Design and procedure functioning together are what create a safe laboratory environment,” says Keene.

In the event of an incident, it is the institution, not the researcher, that is held accountable, and pleading a defense that annual inspections are too expensive to conduct is insufficient.

“According to U.S. guidelines, it is the institution’s responsibility to make sure labs are properly built, maintained, and inspected,” he says.

Commissioning vs. Certification and Validation

Commissioning is the process of making sure that all laboratory equipment and components perform according to their design specifications, and is generally performed for all newly constructed facilities including biocontainment facilities as part of the construction contract. As part of the process, deficiencies and changes should be thoroughly documented. Commissioning does not include a review of biosafety policies and procedures.

Certification is the process of confirming that facility design and operational procedures will prevent pathogens from being released. According to CDC/NIH BMBL requirements, all facilities with a BSL-3 or higher rating must conduct a certification evaluation.  All deficiencies and resolutions must be documented.

Validation is achieved when a facility has been certified to be operationally safe. It is the result of final risk assessment by a team of biosafety professionals and engineers who evaluate the administrative and engineering controls and confirm, or “certify,” that they will function as planned. Facility validation must be reviewed annually.

Common Deficiencies

Of the 22 commissioned labs that WBHT reviewed, none were in full compliance. Of these, five had relatively minor insufficiencies. In some cases, the lapses were procedural, in others, they were the result of design or construction of the facility.

“Sometimes, the design was fine, but the construction was significantly less than perfect,” says Keene.

BMBL guidelines dictate that the lab space must have smooth surfaces that are easily cleanable. Construction lapses included the use of inappropriate materials, exposed wood, gaps in wall penetrations, and inappropriate finishes. Labs must also be sealable in the event of an accident that requires gas decontamination. Common features found in normal labs, such as ceiling-mounted access panels, are incompatible with the criteria of cleanable surfaces that can be sealed.

“One new BSL-3 facility we looked at was very well designed except that there were 15 access doors in the ceiling because all the support services for the outside lab were above the containment lab. According to the BMBL standards, you have to be able to seal all of those access panels. Gaskets are insufficient because, after they are opened several times, they do not provide a sufficient seal. Needless to say, that lab didn’t open,” says Keene.

Concealed sprinklers are another design feature that conflict with the criteria of creating an airtight seal.

“Air has to be able to get in for recessed sprinklers to work, which means there’s a hole for every sprinkler head. The concealed head looks good, but it doesn’t meet the guidelines,” says Keene.

A functional alternative is to run pipes through the ceiling and seal the penetrations with smooth caulk. Keene also recommends covering wall-mounted utility conduits and piping in a sealed chaise for easy cleaning.

Pressures and Procedures

Computer airflow models show that there can also be procedural conflicts with designs involving multiple suites that are negatively pressured against a positive clean corridor.

“Consider a situation where a researcher has a spill of something like mycobacterium tuberculosis, which takes only one or two organisms to cause an infection. From a procedural standpoint, we teach them to stop breathing and get out, but when that researcher opens the door to the hallway, the pressure differential drops to zero. If the pathogen is aerosolized, that aerosol can leak into the positive side. From there it can spread into the other laboratories because they are all under negative pressure,” says Keene.

In this model, the higher the pressure differential, the faster the pathogen moves between rooms. One way to mitigate this problem, from a procedural standpoint, is to create the lowest possible controlled pressure differential between rooms.

“The thing about pressure differentials is that now we can do things we couldn’t do 20 years ago, like electronically interlock the fans; so we have a lot more control,” he says.

HVAC problems can be identified in failure tests conducted during certification. To ensure containment in the event of an accident when the air handling system of a BSL facility fails, the air handling unit must result in either a neutral or negative pressure relationship in the containment laboratory.

“In one facility, everything was operating fine until both the primary and backup fans failed. The laboratory went positive because the building’s air supply was tied into the system and didn’t shut off properly,” says Keene.

Positive vs. Negative

Another common conflict involves the use of positive-pressure cleanroom devices in negative-pressure containment environments.

“We saw another lab where they had put a whole cleanroom ceiling system in and it had to be taken out because pressure differentials could not be achieved as the negative pressure relationship of the laboratory was pulling in the opposite direction against the positive cleanroom seals of the ceiling system,” says Keene.

The exception to this rule are cleanroom pressure monitors that use an internal diaphragm to indicate pressure differentials between rooms without an open hole through the wall.

Value Engineering

Inappropriate value engineering decisions can also result in building deficiencies. Because biocontainment labs are increasingly expensive, value engineering initiatives to cut project costs can result in the use of insufficient materials or design features.

“These are high-requirement facilities. It has to be recognized that they are more expensive. It’s critical that value engineering not be done in a vacuum, and that someone who understands the regulatory requirements must be involved in the process,” Keene says.

It’s also important that all biosafety cabinets, HVAC systems, and prototype technologies be thoroughly tested before being implemented in design.

“You really need to test equipment thoroughly. You can’t just throw something in there because the inventor says it’s the best thing since sliced bread,” says Keene.

Myths and Misconceptions

A common myth about Biocontainment labs is that they are contaminated by default. Keene points out that contamination occurs only if there is an incident outside the biosafety cabinet—the primary containment device.

“If we assume that the lifespan of one of these buildings is 25 or 30 years, it may be contaminated once in that time period. Do you need to install a million dollars’ worth of decontamination equipment for one accident that might happen in 20 years? That is an important decision that has to be made,” says Keene.

Another frequent misconception is that containment labs themselves protect personnel.

“Safety is the result of procedure and engineering systems operating together. We can put a whole lot of money into designing these facilities but, in the end, safety comes down to how people use it,” says Keene.

The design of biocontainment laboratories does not have to be overly sophisticated to be safe. In fact, according to Keene, the simpler they are in design, the safer they are, because good procedures can be used to overcome engineering system deficiencies.

“One thing I have seen is that, when creating procedures, organizations will often just quote the rules. This is not enough. All of these labs are different, so the procedures must be written specifically for each facility, and it’s important that these procedures be reviewed on a regular basis,” says Keene.

By Johnathon Allen