The Sixth Edition of the Biosafety in Microbiological and Biomedical Laboratories (BMBL) manual emphasizes the importance of risk assessment and management, communication among all stakeholders, comprehensive procedures to report accidents and exposures, and a new focus on biocontainment of pathogens affecting agricultural animals. First published in 1984, the BMBL still serves as the cornerstone of biosafety practices for the safe conduct of research throughout the world.
The most recent version, published in 2020 by the Centers for Disease Control (CDC) and the National Institutes of Health (NIH), is thicker than previous manuals with more than 600 pages. Each edition of the manual is an authoritative reference intended for use in an advisory capacity in conjunction with other relevant publications, recommending the best practices for the safe operation and design of microbiological, biomedical, and clinical laboratories.
“The new edition is definitely a risk assessment-based volume, as were most of the others, but this one includes a lot of additional species of bacteria, viruses, and other pathogenic agents,” says Robert Ellis, emeritus biosafety director and emeritus professor in the Department of Microbiology, Immunology, and Pathology at Colorado State University (CSU). “It should be used as an assessment tool to mitigate risks in microbiological, biomedical, and clinical laboratories to ensure the research is safe. The BMBL is the manual the research community looks to for guidance to perform their research in the most efficient, safe, and secure manner.”
Risk Assessment Process
The newest edition delves deeply into the importance of properly assessing and mitigating risks in all phases of research and, if necessary, addressing any adverse incidents or “near misses” that occur. One addition is the recommendation that near misses be added to the records for reporting accidents, exposures, unanticipated absences due to potential laboratory-related infection, and the medical surveillance of potential lab-related illnesses. If an incident or near miss occurs, the lab and building’s culture of safety hinges on an effective communication policy to report risk indicators in a non-punitive manner.
“This is to ensure that such near misses are reported and recognized and can then be addressed procedurally to prevent future incidents,” says Ellis. “Near misses at CSU have been reported for at least a decade and have likely led to the prevention of accidents, exposures, and unanticipated absences due to potential lab-associated infection.”
The risk-management process highlighted in the BMBL outlines six steps:
- Identify hazardous characteristics of the agent and perform an assessment of the inherent risk.
- Identify laboratory procedure hazards.
- Determine the appropriate biosafety level and select additional precautions indicated by the risk assessment.
- Before initiating the research, review the risk assessment and selected safeguards with all relevant stakeholders.
- As part of an ongoing process, evaluate the proficiencies of staff regarding safe practices and the integrity of the safety equipment.
- Regularly revisit and verify risk-management strategies and determine if changes are necessary.
Ellis says CSU started reviewing the risk assessment and safeguards with all relevant stakeholders many years ago and will continue. For example, CSU has an extensive training program for anyone entering the BSL/ABSL-3 research programs. Lab training and extensive mentoring are required before an individual is permitted to work independently in those labs. To facilitate the comprehensive training program, CSU constructed a training lab in one of its buildings in 2008. This particular lab features key card entry, air flow indicators, biosafety cabinets, a locker room, shower, and equipment typically found in BSL-3 labs.
“Ongoing staff training is important with new buildings so you can make that building function correctly and make sure people are trained on that specific building,” says Ellis. “It doesn’t matter what training they’ve had in the past, and just because someone has 20 years of experience in research does not mean they can walk into this next building and operate the same way they are used to operating. Sometimes, the newer people are the ones most likely to pay attention to what is going on in there and be able to operate it correctly, so retraining and refresher training are necessary.”
In addition to proper training, the significance of thorough risk communication is emphasized throughout the BMBL. Users must know what type of pathogens and agents they are working with on a daily basis, abide by the appropriate safety protocols, and have all necessary guidelines in place to address any scenario that might occur. For example, eyewashes are now recommended at lower levels of containment—down to BSL-1—not because of the infectious agents users encounter, but because of the chemical agents.
Major Change in the BMBL Sixth Edition
The manual also discusses loose or open-penned animals, an area not covered in previous editions. When large animals cannot be housed in a primary containment system or ventilated containment cages, certain features of the animal room, such as HEPA exhaust filters and the sealed and pressure-tested room surfaces, act as the primary barriers. Loose-housed and open-penned animals—which refers to large animals such as pigs, sheep, goats, cattle, and horses—may require ABSL-3Ag or ABSL-4Ag containment.
“The biggest changes regarding animal research and containment are going to come in the future with the publishing by the USDA of a manual specifically for loose housing of animals when in containment levels ABSL-2, 3, and 4,” says Ellis. “There were substantial additions to the BMBL 6 Appendix D regarding loose housing of animals, and there are plans for a stand-alone manual dedicated to the containment of these animals. Until this specific manual is published, Appendix D in BMBL 6 is the standard for containment and handling of such species in a loose housed environment.”
Ellis says the information regarding these larger animals was updated to further the necessary research and continued health of the agricultural animal population. He notes that maximizing the health of these animals requires the continued development of new treatments and vaccines for diseases that threaten them.
“The research must be conducted in housing and laboratories that ensure the research, which sometimes involves diseases foreign to the United States, is conducted safely and securely,” he says. “Appendix D addresses guidelines for conducting such research in a safe and secure manner in more detail than in previous BMBL editions. Any research entity, whether university, private, or government, must adhere to these minimum standards in order to safely and securely conduct that research.”
Appendix D stresses biocontainment measures in assessing the risk of working with agricultural pathogens to reduce or eliminate the risk of an agent being released into the environment. The host range of these veterinary pathogens may be limited to animals, although some may also have zoonotic potential and could pose a risk to both humans and animals. This part of the manual describes enhancements that exceed standard practices, procedures, containment equipment, and facility design features common in traditional BSL-2, ABSL-2, BSL-3, ABSL-3, BSL-4, and ABSL-4 facilities.
Stakeholder Value for All Biosafety Level Projects
Obtaining input from all relevant stakeholders is necessary during the risk assessment, risk management, and communication process to ensure consensus on facility design, operation, and communication for all biosafety levels of research and not just research involving agricultural animals.
Administrative officials are often the initial stakeholders brought on board because they control budgetary issues. However, Ellis stresses the valuable input that can be added by biosafety and general safety leaders, maintenance and engineering technicians, lab animal investigators, greenhouse managers (if plants are used in the research), and all other overall building users. Designing a building without including input from relevant stakeholders, such as those who work in the labs, can waste money, time, and effort if modifications are required after construction is complete.
“Investigators are often brought into a committee meeting at the beginning of a project and then forgotten until the building is almost done, and then it is too late to make sure the users’ work needs are addressed,” says Ellis. “Maintenance and engineering also are critical and need to be included throughout every step of the planning, design, and construction. Building and commissioning should be done side by side throughout the construction and handing the building over to the people who will use it.”
Ellis, who worked as CSU’s biosafety director during the design, construction, and operation of most of the university’s current facilities, says communicating with maintenance employees was invaluable. It is a time and money saver to ensure they can easily walk, rather than crawl, through areas where mechanical, electrical, and plumbing equipment is located. If they can comfortably move through these areas on a daily basis, they can listen for slight changes in sounds, like bearings that might be malfunctioning, and correct the issue before it snowballs into a major equipment failure that requires the shutdown of a lab or the entire building.
Ellis says the manual is not meant to be proscriptive, but is rather a guideline of the basics for best practices. As such, there may be variances in how the research is managed and conducted from facility to facility. He suggests including input from all stakeholders throughout the design, construction, and use of the facilities. In addition, he stresses the BMBL is guideline-based, is not a regulatory publication, and should be viewed in conjunction with other documents, rather than as a stand-alone publication.
“The underlying foundation for research relies on the ethics and integrity of the research community to conduct the research in the manner recognized to yield results that can be confirmed by others and which can be used as the foundation for further research,” he says. “The BMBL 6 gives further guidance, especially in the risk-management section, so that all research can continue to be conducted safely and securely.”
By Tracy Carbasho