Clinical Laboratories: Using BSL-2 Plus When Working with Pathogens Transmitted via Inhalation

Clinical laboratories, such as public health or academic labs, commonly conduct procedures involving pathogens that are infectious via inhalation. These pathogens present a significant risk because in addition to getting the individual working with them sick, it can then be quickly transmitted to others. To prevent infection, it is recommended that such work be conducted in a BSL-3 that has the appropriate mechanical systems, personal protective equipment (PPE), and administrative controls.

Yet most often clinical laboratories do not have access to a BSL-3 facility and do not have the funds to create or maintain one. BSL-3 labs can be costly to construct and require routine preventative maintenance and performance validations. The mechanical systems must be recommissioned annually to ensure performance.

So, is there a safe alternative to a BSL-3? While it is not a best practice, with the right precautions and training in place, this work may be conducted safely at Biosafety Level 2 Plus (BSL-2+) containment. Typically, BSL-2+ containment is a laboratory where work with microorganisms is conducted in a BSL-2 lab with biosafety practices and procedures generally found at BSL-3.

Now, let’s examine how you go about implementing a BSL-2+ to safely work with pathogens that are infectious via inhalation.

Start with a Biosafety Risk Assessment

There is no roadmap for implementing a BSL-2+ because it is not a recognized containment level. Before implementing a BSL-2+, the essential first step is to conduct a biosafety risk assessment in accordance with the Centers for Disease Control and Prevention’s (CDC) Biosafety in Microbiological and Biomedical Laboratories (BMBL). The risk assessment will determine the selection of appropriate practices, engineering controls, and PPE to prevent exposure. Remember this process should be fluid. The risk assessment should be treated like a “living document” and updated continuously as procedures, equipment, or infectious agents change.

When working with infectious agents that are transmissible via inhalation, all work must be conducted in a biological safety cabinet with appropriate respiratory protection (N95 respirator or PAPR).

Key Measures of Protection

Consider the four key biosafety program elements that need to be in place to safeguard against exposures when working in a lab:

1. Engineering Controls
2. Administrative Controls
3. Standard Operating Procedures (SOPs)
4. Personal Protective Equipment

When one of these four elements is missing from your program, you must ensure that the other three are highly effective and enforced. Such is the case when working in a BSL-2+ with pathogens that are infectious via inhalation. While BSL-2+ laboratories vary in set up, it is common that the recommended engineering controls such as a dedicated lab mechanical system, HEPA filters, and so on, are missing. This means you must be vigilant in implementing and ensuring adherence to administrative controls, SOPs and the use of PPE.

Training

• The risk communication component of your training program becomes even more critical. Workers need to understand the exposure risks and how the lack of proper engineering controls impacts the procedures they are conducting.
• SOPs for donning and doffing, spill clean-up and exposure response must be thoroughly validated by biosafety personnel.
• Testing biosafety competencies should be part of the training process to ensure laboratory staff are properly trained.

Respiratory Protection and PPE

• The biosafety risk assessment will determine the appropriate respiratory protection. Workers using N95 respirators must be fit-tested annually.
• Proper donning and doffing of PPE will be vital.

Equipment

• Biosafety cabinets must be certified annually.
• Procedures will need to be established for proper decontamination and cleaning of lab equipment.

Administrative Controls

• Your Occupational Health Program must have up-to-date records on health monitoring, vaccinations, immunization status, and availability of prophylactic drugs. As an example, ensuring that PPD testing is conducted annually for lab staff working with tuberculosis (TB) should be part of health monitoring.
• Proper signage clearly identifying biological risks and emergency response procedures.

Case Study: BSL-2+ Clinical laboratory that routinely tests for Mycobacterium tuberculosis

In clinical public health laboratories, routine diagnostic testing for Mycobacterium tuberculosis (MtB) in a BSL-2+ space is commonly performed. Typically, these laboratories are separate and secluded from general laboratories and may or may not contain directional airflow (negative to surrounding spaces).  While MtB is a risk group 3 (RG3) pathogen that is easily transmitted via inhalation (infectious dose of ~10 bacilli), these clinical laboratories adopt modified biosafety practices and procedures for working with RG3 pathogens in a BSL-2 space due to lack of BSL-3 infrastructure.  In this case, strict PPE requirements must be followed, which includes Tyvek suit, double gloves, and either a PAPR or N95 respirator with safety glasses. All manipulations of bacterial cultures must be done inside a biosafety cabinet. SOPs are standardized by a federal regulating body such as the Laboratory Response Network or CDC. Strict adherence to biosafety procedures as well as standardized laboratory testing allows for thorough competency evaluations to take place; staff are evaluated on their microbiological testing techniques as well as biosafety practices. By maintaining high levels of biosafety and clinical testing competencies, in conjunction with strict PPE requirements, it is feasible to conduct work with MtB in a BSL-2+ space at the clinical diagnostic level.

Clinical labs generally conduct standardized procedures that are repetitive in nature, such as diagnostic testing. This makes it a little easier to implement and monitor safe practices than in a research environment where the procedures and materials are continually and rapidly evolving.  However, new emerging infectious diseases are always on the horizon and clinical laboratories are often on the front lines combatting them.

Again, while it is not a best practice, using BSL-2+ containment in the clinical lab setting to conduct work with pathogens that are infectious via inhalation can be a safe and cost-effective alternative to a BSL-3. That is, provided proper precautions are in place and followed.

This approach is not appropriate, and is not recommended, for use of these types of pathogens in the research environment. To learn more about when a BSL-2+ is appropriate for the research environment, read our post, BSL-2 Plus: When and How to Implement It in the Research Environment.

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