The unprecedented global pandemic caused by the novel coronavirus (SARS-CoV-2) and the disease it causes (COVID-19) has brought biosafety to the spotlight. Topics like personal protective equipment (PPE) and respiratory protection are no longer niche topics.

In the research community, we’re seeing a surge of interest in the requisite safety practices for research involving specimens from SARS-CoV-2 positive individuals and COVID-19 subjects. In this blog we will discuss guidelines for implementation of well-established safety practices as provided by the Centers for Disease Control and Prevention (CDC), the Occupational Safety and Health Administration (OSHA), and the American Biological Safety Association International (ABSA International).

Start With a Risk Assessment

In its guidance Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19), the CDC states “[a]ll laboratories should perform a site-specific and activity-specific risk assessment to identify and mitigate risks.”

The CDC’s emphasis on “site-specific” and “activity-specific” assessments is telling—there is no single recipe for doing this. Each risk mitigation plan must be based on the potential biological hazards unique to the activity and the activity’s environment. The CDC notes the assessment and accompanying risk mitigation measure depend on:

  • The procedures performed
  • The hazards involved in the process/procedures
  • The competency level of personnel performing the procedures
  • The facility and its laboratory equipment
  • The resources available

Risk assessments begin with defining the risks associated with the hazard. SARS-CoV-2 is believed to be transmitted through exposure of the mucous membrane such as the eyes, nose, and mouth with:

  • Infectious respiratory droplets, and/or
  • Direct contact with infected body fluids, and/or
  • Exposure to contaminated fomites (e.g., contaminated PPE or used tissue paper)

Some research has shown SARS-CoV-2 may also be transmitted via aerosols.

Developing the Risk Mitigation Plan

With the hazards identified, the next step is discerning the level of risks posed by different experimental procedures starting with specimen origination and transport to the laboratory and ending with waste treatment and disposal.

The OSHA General Duty Clause states employers must provide employees a work environment free from recognized hazards likely to cause serious physical harm or death. Work involving human blood and tissues is subject to the OSHA bloodborne pathogen (BBP) standard; OSHA also requires employers develop a bloodborne pathogen exposure control plan (ECP). Depending on the type of proposed research, the ECP may also serve as a risk mitigation plan. At the very least, the ECP or an existing biosafety manual may provide a starting point for drafting a risk mitigation plan for coronavirus research. Consider the following:

Low-Risk Procedures
Low-risk procedures not anticipated to produce infectious droplets or aerosols include receiving potentially infectious specimens and performing microscope-based assessments of fixed slides. These may be performed in a Biosafety Level 2 (BSL-2) laboratory as long as standard precautions are taken when handling clinical specimens (e.g., proper hand washing practices and the use of appropriate PPE).

Procedures with Potential to Generate Droplets or Aerosols
Procedures with mild to moderate potential to produce infectious droplets or aerosols can be performed in BSL-2 laboratories with enhanced safety practices using an adjoining room from the rest of the laboratory. The room should have a door to restrict access, and occupancy should be limited to only those individuals necessary to perform the procedures. Inward airflow should be exhausted directly out of the lab without recirculation to the facility. Perform these procedures within a certified biosafety cabinet (BSC) (see Figure 1) or another HEPA-filtered aerosol containment device. A risk assessment may require masks or respiratory protection.

Biosafety cabinet image
Figure 1: Biosafety cabinets provide an enclosure to contain droplets and operate under negative air pressure (i.e., suck inward) to protect users and the community from exposure to aerosolized infectious agents.

The two most common procedures conducted on COVID-19 specimens are the real-time polymerase chain reaction (real-time PCR or RT-PCR) and the enzyme-linked immunosorbent assay (ELISA). Obtaining the final readout for these tests involves low-risk procedures. However, infectious droplets or aerosols could be produced during following initial steps:

  • Extracting the viral RNA for RT-PCR
  • Pipetting participant samples into an ELISA plate and the aspiration and washing of these plates

While a typical BSL-2 laboratory provides adequate containment for diagnostic assays as well as quantification of viral and antibody titers, Biosafety Level 3 (BSL-3) containment is required for culturing and characterizing the virus or conducting vaccine challenge studies in animal models. BSL-3 laboratories are designed to contain aerosol-transmissible pathogens.

Transporting Specimens from COVID-19 Patients
Shipping or transport of infectious materials requires a triple-packaging system. Specimens submitted to the CDC for SARS-CoV-2 testing must be shipped as Biological Substance Category B, not Exempt Human Specimens. The transport and shipment of infectious substances are regulated by the US Department of Transportation (DOT) for ground and the International Air Transport Association (IATA) for air. Both agencies require training for anyone packaging, transporting, or shipping hazardous materials (including research participants).

Work Surface Disinfection, Waste Treatment, and Disposal
Simply wiping down a surface with soap and water will not neutralize infectious agents. Equipment and surfaces utilized in conjunction with infectious agents should be disinfected at each step in the experimental process and after any spills. Use an Environmental Protection Agency (EPA)-registered disinfectant labeled to be effective against SARS-CoV-2. When spills occur, the focus must be on protecting research personnel and containing and disinfecting the spill. Once adequate time has passed for droplets to settle and aerosols to be removed by the ventilation system, employees may re-enter the spill area and place disinfectant-soaked paper towels around the spill, moving from the spill periphery toward the center. The manufacturer’s recommended contact time must be allowed for adequate disinfection before disposing of the infectious waste. Requirements for treatment and disposal of infectious waste vary by state, so check your local requirements for specific guidance.

Post-Exposure Procedures
The risk mitigation plan must address procedures to be followed immediately after the exposure, such as washing the exposed site and seeking medical evaluation. Exposed employees may be asked to remain in isolation at home and self-monitor for signs of coronavirus infection for the duration of the 14-day incubation period.

Incident Reporting
The principal investigator/supervisor must be notified of any incidents in the laboratory, and your organization and/or local health department may require various types of reporting. Exposures must be reported as part of the organization’s exposure control plan and documented in the OSHA 300 incident log. IBC-approved research must be reported to the Biosafety Officer/IBC. Spills or accidents resulting in an overt exposure to engineered genetic materials in BSL-2 or greater labs must be reported immediately to the National Institutes of Health (NIH) Office of Science Policy.

Expert Review of Risk Mitigation Plan

It is good practice to have the risk mitigation plan reviewed by a panel of subject matter experts to ensure it comprehensively addresses the research risks and provides the highest level of safety and legal protection to everyone involved. A hospital’s bloodborne pathogen committee may seem like the appropriate panel to review the plan, but such committees typically focus on the standard of care and medical procedures involving sharps rather than a review of laboratory-based research protocols. Assessing risks involving recombinant DNA and infectious agents may be outside the committee’s scope or realm of expertise.

An IBC may be a better fit for reviewing the risk mitigation plan, as IBCs focus on risk assessment and risk mitigation for research involving engineered genetic materials and may cover microbiological safety. Institutions conducting NIH-funded research and research involving engineered genetic materials are required to have IBCs. Sites without IBCs may opt to have their risk mitigation plans reviewed by an independent commercial IBC or another third party. Depending on local requirements, the risk mitigation plan may need to be filed with the local health department.

Conclusion

The initial risk assessment is key to determining the appropriate risk mitigation measures for coronavirus research at your location. Biosafety practices must be customized to the proposed research as well as the existing facility and local regulatory requirements. Proper biosafety measures are critical to conducting safe, high-quality research during this uncertain time.

Note: A version of this content was originally published in Clinical Researcher May 12, 2020.

Not sure where to start with your risk assessment? Contact us for a complimentary risk evaluation and review.

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