Infectious Agents

• Agents that are known to cause human disease in healthy humans and/or have been classified by the NIH Guidelines (see Appendix B) into Risk Groups 2, 3, or 4. 
• Risk Group classification does not account for instances in which an individual may have increased susceptibility to agents. 
• Those agents not listed in Risk Groups 2, 3, and 4, are not automatically or implicitly classified in Risk Group 1, and a risk assessment must be conducted based on the known and potential properties of the agents and their relationship to agents that are listed. 
• The Principle Investigator’s proposed Biosafety Level (BSL) is considered in the IBC’s risk assessment for the final BSL determination and approval. 
• Agents that may impact animals, plants or the environment but are generally not considered infectious to humans - IBC Unit Policy 409 
• i.e., USDA High Consequence Livestock Pathogens, some regulated agents of the USDA/APHIS Plant Pest and Disease Programs, or other animal or plant pathogens.
• The policy also describes agents that are exempt and agents that may go through an expedited review.
• Prions and Prion-like proteins (PLPs) – IBC Unit Policy 410
• PLPs can be transmissible and replicate like an infectious agent, although they have not been shown to be the causative agents of disease.
• Due to their similarity to prions and other infectious agents, PLPs are included in IBC oversight to ensure risk mitigation when using them in some experimental procedures.
• Risk Group 1 agents used in teaching laboratories and/or RG1 recombinant agents
• The IBC decided that all agents used in teaching laboratories (including the use of RG1 agents) require IBC review.

Activities With Materials with Unknown Infectious Agents

Ultimately, an investigator or teacher is responsible for making the decision to submit an IBC application, and the IBC will review any submitted application. The OBAO can assist in a risk assessment of research or teaching activities to help determine if an IBC application is required, recommended, or if an application is not warranted. If research or teaching activities include the use of uncharacterized materials where an infectious agent may be present, the guidance is generally:

• Use of body fluids and blood obtained from apparently healthy humans or non-human primates does not require IBC approval unless samples will be cultured to amplify infectious agents. However, use of these types of samples requires standard precautions as per OSHA regulated standards. Please contact BOHD.
• IBC applications are generally recommended for handling samples from human, animals, or plants that show obvious signs of disease related to covered infectious agents (defined above); or are expected or suspected to contain covered infectious agents (defined above). Required applications depend on the expected agent and the procedures involved (not limited to).
• A risk assessment should consider whether the lab work with materials involves a higher risk than what may be encountered in a non-lab environment.  This should include the procedures that increase the risk of exposure (aerosol formation, enrichment, etc.).
• Samples obtained from the environment (i.e. soil, wastewater, wild animal samples) that may contain infectious agents requires an IBC application if the activities will amplify or enrich for pathogens or if the activities pose a risk to the environment.
• Activities with any materials containing unknown pathogens where the intent is to amplify or enrich for pathogens requires an IBC application.

Resources for Determining Risk Group and Biosafety Levels

ePATHogen - Risk Group Database - note that this site classifies agents with risk groups for both humans and animals. 
ABSA
DSMZ
NIH Guidelines
BMBL

*Please know that the ATCC is not an authority for the University of Minnesota on biosafety, and according to their website, “ATCC has classified products and materials by biosafety level for the purposes of packaging for safe shipment. ATCC determines the biosafety level of a product or material based on our risk assessment as guided by the current edition of BMBL.” The BMBL also states that “The following list of agents is also not comprehensive, and the reader is directed to other information to assist in the risk assessment...” (Pg.147). 

Section 4 Infectious Agent(s) Content Guidance 

1) To activate this section of the application, you must first select “Infectious Agents” within the Activities Include section of the application.  After doing so, an “Add” and “Delete” button will appear in the top right corner of section 4a so that you can populate the table.

2) Add agents to section 4a as individual line items.  Do not group multiple species together in one line item.  Even if you are working with a large number of agents, please list all agents in section 4a (even those that are RG1). 

• Please name the specific agent (i.e. genus, species, etc.)
• An exception to naming is made for samples with unknown infectious agents, except when it is reasonably expected for known infectious agents to be present That is, if expected, list them by line item; if not known, “unknown” may be used (of some other descriptor).

3) In the pop-up window (for each agent), please note we are working to change the text of some questions to be more relevant to the risk assessment. In the meantime, please include in the (b) “Describe…” text box the following information about inherent risks if relevant (there is a character limitation; sentences are not required, but the info needs to be understandable):

• All information to help identify the specifics of the agent, since the specifics impact the risk assessment (i.e. genus, species, subspecies, strain, serovar, type, subtype, variant, ATCC cat#, etc.).
• Capability to infect and cause disease; and/or infectious dose.
• Risk Group.
• Host range, route of transmission, and environmental stability
• Specify if the agent contains r/sNAs or was produced with recombinant methods.
• Name the r/sNAs payloads (e.g. genes, etc.). It is helpful for the risk assessment if a subset of the payloads named in Section 2.b are relevant to specific agents.
• Antibiotic resistance, especially as it relates to clinical treatments for infections with that agent.
• Specify if the microorganism synthesizes a biologically-derived toxin, and if so, the known LD50.
• Specify if you will produce more than 10 liters of culture (relevant to the NIH Guidelines).
• Briefly describe elements of protein-based infectious agents that impact the capability to infect, replicate and/or contribute to disease if these can assist the risk assessment.
• Unknown agent samples that are named as such should characterize what may be present as reasonable as possible for the risk assessment.

4) In the pop-up window and if relevant, complete (f) for the agent administration to animals. Completing this section will activate Safety section 7a)ii so that the proposed animal biosafety level(s) and housing locations can be indicated. Please ensure your IACUC application is current and information is congruent. 

5) In the pop-up window and if relevant, complete g). In rare cases, infectious agents may be used in a clinical study involving human subjects.

• Consider whether the agent’s use in humans may be considered human gene transfer by NIH Definition of the term.  Generally, a recombinant infectious agent used in clinical research would meet this definition. If so, then only the Human Clinical Trials (Section 5.) needs to be filled out.

6) Complete the r/sNA molecule section 2a of the application if the infectious agent is recombinant.  Replication incompetent viral vectors typically used for cell transductions (AAV, adenovirus, lentivirus) should not be accounted for within the Infectious Agents section and instead should only be reported in the r/sNA molecule section 2a.

7) Section 4)b of the application should be completed to indicate where the infectious agents will be stored and any security measures in place for their storage.

8) Include SOPs in the Attachments section to detail how the infectious agents will be handled (PPE, practices, procedures, special containment equipment (e.g. BSC)). Ensure that named agents in the SOPs are congruent with those in the Infectious Agent section.

9) Include the names of the infectious agents within your Biological Decontamination and Spill Clean-up Plan in the box for “Biological Agent(s)/r/sNA/Biological toxin” and describe your routine decontamination procedures and spill clean-up procedures (or check the appropriate boxes of the template).