Managing Biorisk Linked to Rapidly Expanding SARS-CoV-2 Research

COVID-19 was declared a pandemic by the World Health Organization in March 2020 and is caused by the virus known as SARS-CoV-2. A critical component of global efforts to combat a pandemic is biomedical research. ¹ To carry out the research safely, laboratories need to have implemented a well-thought-out biorisk management system (BMS). ² BMS is a systematic approach to addressing biorisk through hazard identification, risk assessment, risk mitigation, and performance monitoring. This system needs to be already implemented during non-pandemic times so that research related to the outbreak can be managed safely during the pandemic period.

Biomedical research, especially on a novel infectious agent, has to be balanced with mitigation measures that are commensurate with the risk. Guidelines for research on SARS-CoV-2 were created early in the outbreak by the US Centers for Disease Control and Prevention ³ and Ministry of Health, Singapore. ⁴ The guidelines stipulate that virus isolation, virus characterization in cell culture, and the manipulation of infectious virus require biosafety level 3 (BSL-3) containment together with site- and activity-specific risk assessment.

The Duke-NUS animal BSL-3 facility is a small annually certified (at BSL-3 containment) 3-lab modular building with about 100 m² of functional floor area. The facility has implemented a BMS that includes a multidisciplinary biosafety committee (BC) that oversees all aspects of safety in the facility. There are facility standard operating procedures (SOPs) and risk assessments (RAs) that cover all facility operations. In addition, every time a research team wants to start a project, they need to submit a project application that includes SOPs and RAs for all the research procedures to be undertaken in that project. This application is reviewed by the BC and after approval is implemented in conjunction with the facility SOPs and RAs.

Since the COVID-19 outbreak, the BC has seen a 15-fold increase in number of project applications to perform SARS-CoV-2-related research. When considering these applications alongside the existing BMS strategy, the following challenges were encountered and addressed:

In the past 6 years that the facility has been in operation, facility SOPs and RAs have been revised and standardized to suit a variety of activities in the facility. This same standardization could not be applied to individual research project SOPs and RAs because in nonpandemic time, applications would be for a variety of experimental procedures using significantly different infectious agents. During this pandemic, all research teams are concentrating on SARS-CoV-2 work, yet risk assessment and mitigation were addressed differently in each of their applications. The BC had to review similar procedures repeatedly in the different applications, and these were then standardized across all applications for research with SARS-CoV-2.

Space and personal protective equipment (PPE) limitations meant that not all projects could commence simultaneously. An independent prioritization committee was established to assess the scientific merit and timeliness of each application to allow for staggered commencement of projects.

The BC membership consisted of many infectious disease researchers. Due to extensive collaboration among the members, many of the project applications carried the names of the BC members who could not review their own applications due to conflict of interest. This was addressed by recruiting ad hoc reviewers with expertise relevant to the research activities described in the application.

Staff in the facility were divided into 3 categories: mentors, independent workers, and those who need supervision. At the start of operations in 2014, an initial set of mentors were selected by the BC and were entrusted with the responsibility of assessing the competency of newcomers in a documented process. Just before the COVID-19 outbreak, staff in the facility were in the mentor or independent worker categories, with no staff who needed supervision. During the outbreak, the number of new staff who needed supervision increased due to the number of new projects from new research teams. This was addressed by capping the ratio of mentors to staff who needed supervision to 1:3 and independent staff to staff who needed supervision to 1:1 while working in the facility. This ratio was based predominantly on the equipment and workflow in each laboratory and has to be determined for each facility and is not a one-size-fits-all solution.

A business continuity plan was implemented where the staff were divided into AM and PM teams to avoid direct contact between the teams in order to facilitate continued operations in the event that one team needed to be quarantined. This also helped to ensure that the occupancy load based on local fire code regulations was strictly followed.

Research procedures that could be performed in a BSL-2 laboratory with BSL-2-enhanced precautions using inactivated virus-derived material were identified. Following established procedures to validate the inactivation procedure and ensuring that the receiving laboratory had adequate risk-mitigation measures in place, inactivated biological samples were moved to a lower containment level. This strategy helped to reduce the number of staff in the BSL-3 facility, thereby reducing risk of exposure and addressing space and PPE limitations.

Conclusion

During nonpandemic times, our facility will continue to carry out infectious disease research on a variety of infectious agents. However, we will have the luxury of time to review the risks and mitigation measures and to get all the necessary approvals when not faced with the challenge of a pandemic. This pandemic has revealed a need to develop a well-thought-out strategy during non-pandemic times that can be rapidly implemented should the next pandemic occur. An effective strategy should include standardization of SOPs and RAs for similar experimental procedures, procedures for inactivation of biological agents, validation of the inactivation procedures, and so on for different categories of potential infectious agents that can cause a pandemic. The strategy can only be successful if it is a collaborative effort among safety professionals and infectious diseases scientists. It should be based on patterns of past pandemics, agents causing it, and advances in science and technology that are likely to be available for research. In our facility, we plan to develop such a biorisk management strategy to be periodically reviewed by the BC and applicable authorities during nonpandemic time so that it is ready for immediate roll out during a pandemic with as little delay as possible.