Risk Assessment & Biosafety Containment Levels

The main goal of the IBC process is to collectively perform a risk assessment of the work proposed and determine the appropriate mitigation measures and Biosafety Containment Levels for the safety of staff, students, and the environment.

Risk Assessment

The PI should make an initial risk assessment of their work based on the Risk Group (RG) of an agent. After the risk group is identified, consideration should be given to the agent’s virulence pathogenicity, dose, environmental stability, route of spread, infectious dose, availability of vaccine treatment, and gene product effects such as toxicity and physiological activity.

Things to take into consideration:

• Any strain that is known to be more hazardous than the parent strain should be handled at a higher containment level.
• Attenuated strains or strains that have demonstrated to have an irreversible loss of virulence factors may qualify for a reduction in containment level compared to the Risk Group assigned to the parent strain.
• Replication incompetent lentivirus, an agent with a Risk Group 3 origin, could be requested to be downgraded to a lower containment.
• Combinations of recombinant sequences within a new biological context may result in an organism whose risk could be higher than that of the parent organisms or sequences.
• Pseudotyping of viruses can result in a higher containment level than the parent strain due to alteration to its tropism (creation of an amphotropic or pantropic virus rather than the ecotropic parent strain). 
• The types of manipulations that are planned with the agents.
• RG2 dengue viruses may be cultured under Biosafety Level (BSL) 2 conditions, but when agents are used for animal inoculations, a higher containment level is often advised.

Risk Groups

Agents are classified into four Risk Groups (RGs) according to their relative pathogenicity for healthy adult humans. Risk group does not account for instances in which individuals may be more susceptible to such agents due to preexisting conditions, use of medications, compromised immunity, or pregnancy.

Risk Group 1 (RG1) – agents are not associated with disease in healthy adult humans.

Risk Group 2 (RG2) – agents are associated with human disease which are rarely serious and for which preventative or therapeutic interventions are often available.

Risk Group 3 (RG3) – agents are associated with serious or lethal human disease for which preventative or therapeutic interventions may be available.

Risk Group 4 (RG4) – agents are likely to cause serious or lethal human disease which preventative or therapeutic interventions are usually not available. 

Biosafety Levels

The PI is asked to propose biosafety levels for each component of their work based on their risk assessment. For example, transformation of E. coli has different risks associated with it than the use of lentivirus and would therefore have different biosafety levels proposed. Each type of experiment should be listed in Table 7ai of the application and a separate biosafety level should be proposed by experimentation type.

There are four biosafety levels (BSLs) which consist of combinations of laboratory practices and techniques, safety equipment, and laboratory facilities (the University has BSL1, BSL2, and BSL3 facilities but does not have any BSL4 certified facilities). Biosafety levels are not equivalent to Risk Groups (RG). The risk group of an agent is one factor that should be considered when determining biosafety level but other factors such as mode of transmission, gene expression, procedures, and experience of staff should all be determining factors in BSL.

BSL1

BSL1 is a basic level of containment which relies on standard microbiological practices with no special primary or secondary barriers recommended other than a sink for hand washing.

• Examples: transformation of E. coli, transformation of non-infectious bacteria, use of non-exotic transgenic plants.
• PPE: generally includes gloves and a lab coat.
• Work is generally performed on the benchtop rather than in a higher containment setting such as a biosafety cabinet.

BSL2

BSL2 practices, equipment, and facility design and construction are applicable to clinical, diagnostic, teaching, and other laboratories in which work is done with a broad spectrum of moderate-risk agents that present in the community and associated with human diseases of varying severity.

• Covers work with human-derived blood, body fluids, tissues, or primary human cell lines where presence of infectious agents is unknown.
• PPE- generally includes a lab coat and gloves.
• Enhanced PPE (lab coat, double gloves, disposable sleeves, eye protection, and N95 face mask) for work with higher risk agents like lentivirus where oncogenic potential exists.
• A biosafety cabinet is generally required as well as hand washing sinks and waste decontamination facilities (autoclave or biohazard red bags). 

BSL3

BSL3 practices, safety equipment, and facility design and construction are applicable to clinical, diagnostic, teaching, research, or production facilities in which work is done with indigenous or exotic agents with a potential for respiratory transmission, and which may cause serious and potentially lethal infection.

• More emphasis is placed on primary and secondary barriers to protect personnel, the community, and the environment from exposure to potentially infectious aerosols. 
• All laboratory manipulations should be performed in a BSC or other enclosed equipment, such as a gas-tight aerosol generation chamber. 
• Secondary barriers for this level include controlled access to the laboratory and ventilation requirements that minimize the release of infectious aerosols from the laboratory.

BSL4

There are no BSL4 facilities on campus. For further information on the practices, safety equipment, and facility design of BSL4 laboratories, please consult the BMBL or the NIH Guidelines.

Responsibilities of the PI When Performing a Risk Assessment

The PI is expected to provide the initial risk assessment as the subject expert on the r/sNA molecule, infectious agent, or biological toxin that they propose to work with.

The PI should: 

• Describe how staff, students, and the environment will be protected from potential hazardous exposures.
• Focus on biological risks rather than chemical hazards or risks.
• Describe the work with r/sNA molecules, infectious agents, or biologically-derived toxins from their initial use/generation through their inactivation or decontamination to prevent exposure to personnel and the environment.

Goals of the IBC and Admin When Reviewing an Application

The IBC Administrative staff will perform an initial review of an application upon receipt and looks at the following:

• Does the work fall under IBC purview?
• Checks for completeness and consistency in the study objectives, application sections, and SOPs.
• Checks Attachments for:
• Required PPE for personnel.
• Building names and room numbers for the laboratory locations used.
• Used to determine if the containment level is appropriate for the work proposed.
• Descriptions of the equipment used to ensure adequate containment of the biological agents (use of a biosafety cabinet, use of secondary containment for transportation, or use of sealed rotors for centrifugation).
• Decontamination and/or deactivation methods for the biological agents or biologically derived toxins in oversight.

An application will be reviewed by the IBC according to its responsibilities named in the NIH Guidelines:

• Perform an independent assessment of the containment levels required by the NIH Guidelines for the proposed research
• Assess the facilities, procedures, practices, and training and expertise of personnel involved in the activities described in the application.
• Assess biosafety issues related to research under IBC purview involving human subjects (e.g., administration, shedding).
• Ensures emergency plans covering accidental spills and personnel contamination are in place related to the activities described in the application.