FAQs: Select Agents

Select agents is a term used by the government to indicate specifically regulated pathogens and toxins. Both the Department of Health and Human Services acting through the Centers for Disease Control (HHS-CDC) and the United States Department of Agriculture (USDA) acting through the Animal and Plant Health Inspection Service (APHIS) maintain lists of such pathogens and toxins. Some agents appear on both lists and are termed overlapping agents—current alphabetical list of all select agents and toxins. Agents are listed in the far left column. The agents on this list are thought to pose a threat as potential weapons of bioterrorism and/or could represent a severe threat to human health and safety and animal or plant health and/or products . The use, possession, and transfer of these agents is regulated by the federal government. Several laws and government regulations are applicable to these agents and these a listed below.

Excluded Strains of HHS and USDA Select Agents and Toxins

Based upon consultations with subject matter experts and a review of relevant published studies and information provided by the entities requesting the exclusions, the Federal Select Agent Program has determined that the following attenuated select agent strains or less toxic select toxins are not subject to the requirements of the select agent regulations.

An excluded select agent strain or modified toxin will be subject to the regulations if there is a reintroduction of factor(s) associated with virulence, toxic activity, or other manipulations that modify the attenuation such that virulence or toxic activity is restored or enhanced. In addition, excluded select agent strains or modified toxins are not exempt from the requirements of other applicable regulations or guidelines (e.g., NIH guidelines, USDA/APHIS permits, etc.).

Nontoxic HHS toxins, Section 73.3 (d)(2)

  • Botulinum neurotoxins
  • Conotoxins
  • Staphylococcal Enterotoxins (SE)

Excluded Toxins Modified to be Less Potent or Toxic, Section 73.3 (e)

  • Tetrodotoxin

Excluded Attenuated Strains of HHS Select Agents, Section 73.3 (e)

  • Botulinum neurotoxin producing species of Clostridium
  • Coxiella burnetii
  • Eastern Equine Encephalitis virus
  • Ebola virus
  • Francisella tularensis
  • Junin virus
  • Lassa fever virus
  • Mpox virus
  • SARS-Coronavirus
  • Yersinia pestis

Excluded Attenuated Strains of Overlap Select Agents, Section 73.4 (e) and 121.4 (e)

  • Bacillus anthracis
  • Brucella abortus
  • Brucella melitensis
  • Burkholderia mallei
  • Burkholderia pseudomallei
  • Rift Valley Fever Virus
  • Venezuelan Equine Encephalitis virus

Attenuated Strains of USDA-only Select Agents Excluded, Section 121.3 (e)

  • African swine fever viruses
  • Avian influenza virus (low pathogenic)
  • Avian influenza virus (highly pathogenic)
  • Foot-and-mouth disease virus

Permissible Toxin Amounts

The following toxins are not regulated if the amount under the control of the principal investigator, treating physician or veterinarian, or commercial manufacturer or distributor does not exceed, at any time, the aggregate toxin limit specified in the HHS select agent and toxin regulations [42 CFR 73.3(d)(7), or the amounts indicated in the table below.

 

HHS Toxins [§73.3(d)(7)]                Amount

Abrin                                                            1000 mg

Botulinum neurotoxins                            1 mg

Short, paralytic alpha conotoxins          100 mg

Diacetoxyscirpenol (DAS)                       10,000 mg

Ricin                                                             1000 mg

Saxitoxin                                                     500 mg

Staphylococcal Enterotoxins                  100 mg

(Subtypes A, B, C, D, and E)

T-2 toxin                                                    10,000 mg

Tetrodotoxin                                             500 mg

Depending on which documents are under review, the above mentioned terms may be used. Listed below is an explanation of the terminology and how these terms relate to one another.

  • Risk Groups – This is the classification assigned to microorganisms based on their relative pathogenicity to healthy adult humans by the NIH Guidelines for Research involving Recombinant DNA Molecules (NIH Guidelines). There are 4 groups. They are as follows:
    • Risk Group 1 – Agents not associated with disease in healthy adult humans
    • Risk Group 2 – Agents associated with human disease which is rarely serious and for which preventive or therapeutic interventions are often available.
    • Risk Group 3 – Agents associated with serious or lethal human disease for which preventive or therapeutic interventions may available (high individual risk low but low community risk).
    • Risk Group 4 – Agents likely to cause serious or lethal human disease for which preventative or therapeutic interventions are not usually available (high individual and high community risk). A list of microorganisms classified by risk group can be found in Appendix B of the NIH Guidelines. There are numerous organisms in this appendix which are not select agents.
  • Biosafety Levels – Biosafety levels (BSL) refer to the combination of laboratory practices and techniques, safety equipment and laboratory facilities under which the project can be conducted safely. There are four biosafety levels (1-4). The risk group an agent is classified under, attenuation or inactivation of the agent, the type of work being conducted, and the amount of the agent being used are all factors used in determining the biosafety level assessment.
  • Priority Levels – Priority levels were assigned by CDC and NIAID to some select agents and other infectious agents based on the criteria listed below. Although, the agents assigned to category A, B, and C are the same for both the CDC and NIAID, the NIAID also took into account the potential for the agent to be weaponized, the lack of a safe and effective vaccine, and the lack of specific diagnostic tests and/or effective treatments in assigning a priority category to agents. Moreover, the NIAID Strategic Plan for Biodefense Research (February 2002) specifically stated that the plan should not be limited by preexisting CDC lists when assigning priority categories and should remain flexible and based on the characteristics that make an agent a feasible threat to civilian populations. Some agents listed under category B are not select agents (e.g., food and water-borne pathogens).
    • Category A – Highest Priority. These are based on the threat to public safety and the potential for use as weapons for bioterrorism. These agents can be easily disseminated or transmitted from person to person; result in high mortality rates and have the potential for major public health impact; might cause public panic and social disruption; and require special action for public health preparedness.
    • Category B – Second Highest Priority- These agents are moderately easy to disseminate; result in moderate morbidity rates and low mortality rates; and require specific enhancement of diagnostic capacity and enhanced disease surveillance.
    • Category C – Third Highest Priority- These agents include emerging pathogens that could be engineered for mass dissemination in the future because of availability; ease of production and dissemination; and potential for high morbidity and mortality rates and major health impact.
  • Restricted Agents – This terms refers to select agents and is used in the NIH Guidelines.

For more information on select agents with their Risk Group status and Priority Category, use our comparison table.

Any investigator contemplating the use of a select agent in their research within the next year should contact the UIC Environmental Health and Safety Office (EHSO) at 996-7411 to begin the process of select agent registration. The process can be lengthy, requires background checks of all personnel that will have access to the agent, and may require remodeling of laboratory space. DO NOT WAIT TO BEGIN THIS PROCESS!!! Listed below are a number of issues that must be considered prior to completion of the registration process and additional units on campus that must be contacted.

  • Registration of entity (Section 1 and 2 of registration form)
    This applies to registration of the institution. Federal law requires that each institution that will use, possess, or transfer select agents be registered. UIC is a registered institution with both the CDC and USDA. The entity must also identify a Responsible Official (RO), and alternative RO. These individuals are responsible for ensuring management oversight of the implementation of the select agent regulations and they provide a point of contact for the entity.
  • Registration of agent (Section 3 and 4A of registration form)
    Each agent that will be used, possessed by, or transfer to or from an entity must be registered and the principle investigator using, possessing, or transferring each specific agent must be identified.
  • Biosafety level evaluation (Section 4A of registration form)
    For each agent/investigator/laboratory facility- the following information must be provided. The EHSO will assist investigators in completing this portion of the application

    • Agent/Toxin Name
    • Facility Agent ID (e.g., specific identification used to identify a specific agent, toxin or derivative at that facility)
    • Form of the agent being used and type of use (e.g., viable, rDNA, genomic, toxin, small animal use, large animal use, or large scale production)
    • Location of Use and Storage- the laboratory room and bldg and the storage room and bldg must be identified
    • Laboratory Safety Level- This is the biosafety assigned to the specific use and form of the agent for a specific investigator and specific laboratory.
  • Facility evaluation (Section 5 of registration form)
    Each investigator for each laboratory must complete the laboratory information section. The EHSO along with additional units (underlined) will assist investigators with this process. The laboratory information is a detailed description of the following:

    • Agent Specific Information (these questions need to be answered for each principle investigator/laboratory supervisor) – Agent Name, Strain Designation, Date Acquired, Address of Facility from which Agent/Toxin was Acquired and Select Agent Registration number, if applicable, Facility Agent ID, Source of Isolate, Unique Diagnostic Characteristics, Reference to Published Sequence information, and Host Range.
    • Laboratory Specific Information (these questions need to be answered for each laboratory room where select agents are used or stored. If all laboratories with the same biosafety level under the control of one principle investigator/laboratory supervisor meet the same criteria, then all laboratory rooms may be listed on one form and only one form needs to be submitted). Many of these questions will require working with EHSO, UIC police, UIC facility management, BRL, the IBC, and the ACC. In addition,
      1. Floor plans (identifying location of fume hoods, eyewash stations, sinks, biosafety cabinets, freezers, centrifuges, etc.)
      2. HVAC system
      3. Biosafety cabinets
      4. BSL3 specific questions
      5. ABSL2 or ABSL3 animal specific questions. In addition to completion of this information on select agent application, submission and approval of a protocol by UIC ACC is required. Contact the ACC office.
      6. Safety – procedures, equipment, waste disposal, accidental spills and training (what, when, how, proficiency, documentation). An SOP should be developed for each laboratory handling select agents. Training will be conducted by UIC Biosafety officer.
      7. Security/Access – In addition to the Background check conducted by the Department of Justice, each lab must have a site-specific security assessment conducted by the UIC police. Investigators should contact Demetruis Anderson at 355-3466 when they begin the select agent registration process. This will include assessing the security of the facility, security of the agent, and security of the data, as well as, key card assess to approved personnel. Training on security procedures must also be documented.
      8. Recordkeeping practices – Inventory control and report of theft, loss, or release of select agents or toxins- Each laboratory must maintain a log of use/destruction of the agent. If a loss, theft or release of the select agent is detected, the investigator must immediately contact EHSO to report it. The theft, loss or release must be reported immediately by telephone to the appropriate agencies by the RO and within 7 calendar days a form (CDC 0.1316/APHIS 2043) must be completed by the RO and sent to the appropriate agency.
      9. Infectious agent specific questions. In addition to completion of this information on select agent application, submission and approval of a protocol by UIC IBC is required. Contact the IBC office.
      10. rDNA specific questions. In addition to completion of this information on select agent application, submission and approval of a protocol by UIC IBC is required. Contact the IBC office.
      11. Toxin specific questions. In addition to completion of this information on select agent application, submission and approval of a protocol by UIC IBC is required. Contact the IBC office.
  • Background check of Personnel
    A background check of all personnel who will work with or have access to any select agent is required. Department of Justice (DOJ) forms must be completed and each researcher must be fingerprinted. Only personnel approved by the DOJ will be allowed access to select agents.
  • Health Related Issues
    medical surveillance, vaccination requirements, and knowledge of signs and symptoms of exposure. In addition to contacting the EHSO, investigators should discuss these issues with University Health Service Director, David Marder (996-7420).

Contact EHSO at 996-7411 to complete this process. All shipping and receiving of select agents must be done by the EHSO and may only be done between registered entities. The CDC FORM EA101 / APHIS FORM 2041 – Report of Transfer of Select Biological Agents and Toxins must be completed. Portions of this form need to be filled out by both the recipient RO and the sender RO. The sequence for completing this form (who, what and when) is shown below. In addition, if investigators are planning on obtaining select agents from outside the United States, an APHIS import permit must be obtained.

  • Requestor RO – complete block 1 – requestor (recipient) information
    • Entity name
    • Entity Registration number(s)
    • Recipient name and contact information (must be registered)
    • Principle investigator name and contact information (if different from recipient)
    • Requestor RO name and contact information
  • Requestor RO – Complete block 2- select agent description
    • Indicate if organism, toxin, and/or rDNA organism/molecules with appropriate strain/type information.
    • Indicate intended use: research, diagnostic, production, other (explain)
  • Requestor RO – Fax form and registration certificate to sender.
  • Sender RO – complete block 3- sender (transferor) information
    • Entity name
    • Entity Registration number(s)
    • Sender name and contact information (must be registered)
    • Principle investigator name and contact information (if different from sender)
    • Sender RO name and contact information
  • Sender RO – fax form to CDC or APHIS to obtain verification number.
  • Sender RO – once CDC or APHIS approval is obtained- complete block 4 (except for date of receipt)- shipping information
    • Select agent
    • Characterization of agent
    • Number of vials
    • Form of agent
    • Amount per vial
    • Total Amount
    • Concentration/vial
    • Number of primary receptacles/outer packages
    • Number of outer packages
    • Carrier and waybill tracking number
    • Shipping Date
    • A return receipt may also be required for some select agents.
  • Sender RO – oversees packaging and shipment of agent to recipient. Sends shipment.
  • Recipient RO – Receives agent
  • Recipient RO – Complete block 4
    • Enter date of receipt
    • Verify that what was shipped was received
    • Within 2 business days provide fax or paper copies of completed form to CDC or APHIS and sender RO.
  • Sender and Recipient RO – retain paper record for 3 years, or retain record 3 years after agent consumed or destroyed, which ever is longer. When the select agent from a transfer is depleted or destroyed, the RO of the facility must complete the appropriate information in block 4 of the form and fax a copy of the form to the CDC or APHIS.

How do I gain key card access to a select agent facility?
All researchers who will be working with select agents must complete the select agent registration process, complete the background security check with the FBI and complete a security risk assessment with the UIC Police by contacting Demetruis Anderson at 355-3466. Key card assess must be approved by the UIC Police.

Any investigator using rDNA, infectious agent and/or a toxin, regardless of whether these items are select agents, must complete an Institutional Biosafety Committee protocol. Policies, instructions and protocol forms can be found on the IBC web site. Investigators should contact the IBC office with questions.

Registration lasts for three years. Registration will need to be renewed for any investigator who wishes to continue working with select agents. If at that time the investigator is no longer working with the select agent, but still possesses it, then registration must be renewed.

Any change (e.g., how the agent is being used, how much, where, by whom, etc.) in the use of a select agent must be reported to the EHSO (996-7411) prior to initiation of the change. This is essential to determine if an amended registration is necessary. In addition, changes in select agent use should be reported to the IBC (996-7427) prior to initiation to determine if a modification of the IBC protocol must be approved.

Select Agent Risk Group Comparison