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BIOLOGICAL RISK ASSESSMENTS

1.

It is the responsibility of the principal investigator or laboratory supervisor to conduct a risk assessment to determine the proper work practices and containment requirements (Biosafety Level) for work with biohazardous material.


2.

The selection of an appropriate biosafety level when working with nucleic acids, a particular agent or type of equipment, laboratory animals, cell cultures, etc. is dependent upon a number of factors and must be based on the risk assessment. Two of the most helpful tools available for performing a microbiological risk assessment is the listing of Risk Groups (RG) for microbiological agents found in the Classification of Human Etiologic Agents on the Basis of Hazard (Appendix B) and the Agent Summary Statements found in Section 8 of the Biosafety in Microbiological and Biomedical Laboratories (BMBL)


3.

In deciding on the appropriate containment for an experiment, the first step is to assess the risk of the agent itself. Use the links above to determine the Risk Group for the agent(s). The Risk Groups range from 1 (least hazardous) to 4 (most hazardous) and are based on an assessment of their ability to cause disease in humans and the available treatments for such disease.

 

4.
Once the Risk Group of the agent is identified, this should be followed by a thorough consideration of its hazards, how the agent is to be manipulated and other factors. Factors to be considered in determining the level of containment, include agent factors such as:
  a. Virulence
  b. Pathogenicity of the agent and infectious dose
  c. Potential outcome of exposure
  c. Route of spread
  d. Communicability
  e. Other routes of infection, resulting from laboratory manipulations (parenteral, airborne, ingestion)
  f. Stability of the agent in the environment
  g. Allerginicity
  h. Concentration of the agent and volume of concentrated material to be manipulated
  i. Presence of a suitable host (human or animal)
  j. Information available from animal studies and reports of laboratory-acquired infections or clinical reports
  k. Laboratory activity/operations planned (sonication, aerosolization, centrifugation, etc.)
  l. Any genetic manipulation of the organism that may extend the host range of the agent or alter the agent's sensitivity to known, effective treatment regimens
  m. Local availability of effective prophylaxis, vaccine or therapeutic interventions
  n.

Gene product effects such as toxicity

 

Any strain that is known to be more hazardous than the parent (wild-type) strain should be considered for handling at a higher containment level. Certain attenuated strains or strains that have been demonstrated to have irreversibly lost known virulence factors may qualify for a reduction of the containment level compared to the Risk Group assigned to the parent strain.

When assessing the hazards of a newly attenuated pathogen, experimental data should support a judgment that the attenuated pathogen is less hazardous than the wild-type parent pathogen before making any reduction in the containment recommended for that pathogen.

While the starting point for the risk assessment is based on the identification of the Risk Group of the parent agent, as technology moves forward, it may be possible to develop an organism containing genetic sequences from multiple sources such that the parent agent may not be obvious. In such cases, the risk assessment should include at least two levels of analysis. The first involves a consideration of the Risk Groups of the source(s) of the sequences and the second involves an assessment of the functions that may be encoded by these sequences (e.g., virulence or transmissibility). It may be prudent to first consider the highest Risk Group classification of all agents that are the source of sequences included in the construct. Other factors to be considered include the percentage of the genome contributed by each parent agent and the predicted function or intended purpose of each contributing sequence. The initial assumption should be that all sequences will function as they did in the original host context.

The Principal Investigator and Institutional Biosafety Committee must also be cognizant that the combination of certain sequences in a new biological context may result in an organism whose risk profile could be higher than that of the contributing organisms or sequences. The synergistic function of these sequences may be one of the key attributes to consider in deciding whether a higher containment level is warranted, at least until further assessments can be carried out. A new biosafety risk may occur with an organism formed through combination of sequences from a number of organisms or due to the synergistic effect of combining transgenes that results in a new phenotype.

 

5.

Identify laboratory procedure hazards. Occasions will arise when it will be necessary to assign a biosafety level higher than that recommended in these guidelines depending on the type of manipulation. Identify agent concentrations, suspension volume, equipment and procedures that generate small particle aerosols and larger airborne particles (droplets), and the use of sharps. Also, procedures involving animals present hazards such as bites, scratches, exposure to zoonotic agents and experimentally generated infectious aerosols. For example, an agent that is assigned to Risk Group 2 may generally require Biosafety Level 2 facilities, equipment, practices and procedures for safe conduct of work. However, if particular experiments require the generation of high-concentration aerosols, then Biosafety Level 3 may be more appropriate to provide the necessary degree of safety, since it ensures superior containment of aerosols in the laboratory workplace. Also, the Risk Group 2 dengue viruses may be cultured under the Biosafety Level (BSL) 2 containment; however, when such agents are used for animal inoculation or transmission studies, a higher containment level is recommended.

 

6.

Make a determination of the appropriate biosafety level and select additional precautions indicated by the risk assessment. A final assessment of risk based on these considerations is then used to set the appropriate containment conditions or biosafety level for the experiment. The appropriate containment level or biosafety level may be equivalent to the Risk Group classification of the agent or it may be raised or lowered as a result of the above considerations. The Institutional Biosafety Committee will approve the risk assessment and the biosafety containment level for recombinant or synthetic nucleic acid experiments or biological research.

 

7.

In general, the biosafety level used for activities involving infectious agents or infected animals must be commensurate with that required for the agent of highest virulence known, or likely to be encountered in the course of the contemplated work.

 

8.

Evaluate the proficiencies of staff regarding safe practices and the integrity of safety equipment. The Principal Investigator must ensure that laboratory workers have acquired the technical proficiency in the use of microbiological practices and safety equipment required for the safe handling of the agent, and have developed good habits that sustain excellence in the performance of those practices. An evaluation of a person's training, experience in handling infectious agents, proficiency in the use of sterile techniques and Biological Safety Cabinets (BSCs), ability to respond to emergencies, and willingness to accept responsibility for protecting one's self and others is important insurance that a laboratory worker is capable of working safely.

The Principal Investigator must also ensure that the necessary safety equipment is available and operating properly. The Principal Investigator should have all equipment deficiencies corrected before starting work with an agent.

 

9.

Research involved with materials derived from humans (e.g., blood, tissue, cell lines) or when working with HIV, HBV or from HIV or HBV infected or inoculated animals, or other Bloodborne Pathogens must maintain compliance with OSHA's Bloodborne Pathogens Standard, handled under Universal Precautions (treating all material as if infectious) and performed in compliance with Biosafety Level 2 guidelines.

 

10.
Refer to the following resources to assist in your risk assessment:
a. NIH Recombinant and Synthetic Nucleic Acid Molecules Guidelines, including Appendix B (Risk Groups), G (Physical Containment) and I (Biological Containment)
b. Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition, (CDC/NIH Agent Summary Statements and Biosafety Level Criteria)
c. American Biological Safety Association (ABSA), Risk Group Classification for Infectious Agents
d. Pathogen Safety Data Sheets (PSDS) and Risk Assessment
e. WHO (World Health Organization), Biosafety Manual
  f. American Type Culture Collection (ATCC)
  g. EHRS's Quick Guide to a Biological Risk Assessment

 

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