Biological Safety Manual - Chapter 14: Select Agents and Toxins

Title

Biological Safety Manual - Chapter 14: Select Agents and Toxins

Introduction

The U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Department of Agriculture (USDA) have designated certain biological agents and toxins as Select Agents, because they have the potential to pose a severe threat to public, animal or plant health, or to animal or plant products. These materials require federal registration and approval to receive, posses, or transfer them.

The 1996 Antiterrorism and Effective Death Penalty Act first regulated the transfer of Select Agents between persons and institutions. The 2001 USA Patriot Act prohibits certain individuals from shipping, transporting, or possessing a Select Agent. The 2001 North Carolina Biological Agents Registry requires the University of North Carolina at Chapel Hill ("UNC-Chapel Hill" or "University") to register all Select Agents with the North Carolina Department of Health and Human Services.

The 2002 Public Health Security and Bioterrorism Preparedness and Response Act require federal registration for possession and transfer of the following:

• Select Agents,
• plant pathogens, and
• high-consequence livestock pathogens and toxins.

The U.S. Department of Health and Human Services (DHHS) regulates Select Agents targeting public health (42 CFR 73). The USDA regulates Select Agents targeting agriculture, animal, and animal products (7 CFR 331 and 9 CFR 121). Select Agents regulated by both HHS and USDA are called “overlap” Select Agents. Investigators at UNC-Chapel Hill using overlap Select Agents need to comply only with the DHHS rules (42 CFR 73).

Faculty, staff, and students may access or possess a Select Agent only for reasonably justified bona fide research purposes. The UNC-Chapel Hill Office of Environment, Health and Safety (EHS) manages UNC-Chapel Hill’s compliance program for these Select Agents under the oversight of the Institutional Biosafety Committee (IBC).

EHS tracks the following items:

• Select Agent use on campus, including the specific Select Agent;
• the Principal Investigator (PI), the PI's laboratory personnel, and their training;
• where the Select Agent is used;
• security measures; and
• facility engineering controls.

Please contact EHS for help in complying with these rules, policies, and procedures.

Please contact EHS immediately if you discover a Select Agent in your lab that has not been registered.

Please visit the U.S. Government's "Federal Select Agent Program" website for a complete list of Select Agents and Toxins and exclusions.

Table of Contents

1. Definitions
2. Registration
3. Select Agent Authorization
4. Requirements for Select Agent Workers
5. Required Plans and SOPs
   1. Biosafety Plan
   2. Incident Response Plan
   3. Security Plan
   4. BSL-3 Laboratory Standard Operating Procedures
6. Required Documentation
7. Annual Inspections
8. Permissible Toxin Amounts (HHS Toxins [§73.3(d)(7)])
   1. Due Diligence Provision: [§ 73.3(d)(7)(i)]

I. Definitions

• Access: The freedom or ability to obtain or make use of or the ability to carry, use or manipulate Select Agents.
• Biosafety Plan (BSP): A written BSP that is commensurate with the risk of the Select Agent or Toxin, given its intended use. The BSP must contain sufficient information and documentation to describe the biosafety and containment procedures for the Select Agent or Toxin, including any animals (including arthropods) or plants intentionally or accidentally exposed to or infected with a Select Agent.
• Personnel Suitability: Personnel with access to Select Agents or Toxins should not display behaviors determined by UNC-Chapel Hill that would increase the risk of a theft, loss, or release of a Select Agent or Toxin.
• Repository Materials: Agents for which Select Agent inventory records will be maintained. These include:
  • non-excluded Select Agent toxins,
  • virulent Select Agents,
  • nucleic acids that can produce infectious forms of Select Agent viruses,
  • nucleic acids that encode for functional forms of Select Agent toxins (if they can be expressed in vivo or in vitro or are in a vector or recombinant host genome), and
  • animal tissue containing virulent Select Agents.
• Responsible Official (RO): The individual designated by UNC-Chapel Hill with the authority and responsibility to act on behalf of UNC-Chapel Hill to ensure compliance with Section 9 of the Select Agent regulations. UNC-Chapel Hill has designated the Executive Director of EHS to be the Responsible Official. The Biological Safety Officer and the Associate Biosafety Officer serve as Alternate Responsible Officials (ARO).
• Select Agent Laboratory: A room or suite of rooms, such as a laboratory or animal care area, which EHS has authorized for the storage or use of a Select Agent. This area must be delineated in the Laboratory Safety Plan and meet the security standards described in the Security Plan. In most cases, security measures are also in place outside of the Select Agent Laboratory, which creates a larger secure area.
• Security Risk Assessment (SRA): An U.S. Federal Bureau of Investigation (FBI) procedure for obtaining approval under Section 73.10 for access to a Select Agent or Toxin. As described below, an approved FBI SRA is required for UNC-Chapel Hill’s RO, AROs, Select Agent Authorized Users, other Select Agent Workers and any other person who, in the normal scope of their duties, would have (or be permitted) unescorted access to a Select Agent or Toxin. Individuals are considered “SRA-approved" when the FBI grants approval. Access approval is valid for a maximum of three (3) years.
• Select Agent: Biological agents and toxins listed in 42 CFR 73, 7 CFR 331, 9 CFR 121, and the North Carolina Biological Agents Registry Law.
• Select Agent Authorized User: A PI who is authorized by EHS and the IBC to work with a Select Agent. The Select Agent Authorized User may designate an SRA-approved co-PI for certain responsibilities as described in this chapter.
• Select Agent Tracking System: A secure web-based information system used at UNC-Chapel Hill to meet the inventory, recordkeeping, and tracking requirements.
• Select Agent Worker: A student, staff member, visiting scientist, or faculty member (including the Select Agent Authorized User) who has obtained an SRA, has satisfied training requirements, and has met all other applicable UNC-Chapel Hill training, occupational health, and EHS requirements.

II. Registration

Contact EHS to begin the registration process if you wish to begin work with a Select Agent or Toxin. Before possessing, using, or receiving Select Agents, the University must register with the CDC and/or the USDA and demonstrate compliance with specific safety and security standards for handling these Select Agents. Registration includes SRA and criminal background checks for individuals seeking access to the Select Agents, security plans, and inventories. EHS will coordinate and submit the registration, and any updates. The registration is valid for three (3) years.

PIs must notify EHS before making any changes so that the CDC is promptly notified and to obtain prior approval. Changes that require notification include modifications to the list of individuals designated for access to Select Agents, changes in work locations, or changes in protocols or objectives of the studies.

The PI or Co-PI must contact EHS to request authorization for access for an individual to a Select Agent Laboratory. EHS will send an amendment to the CDC. The individual must fill out a lab worker registration form. Select Agent Workers must notify EHS immediately when they intend to terminate employment in the Select Agent Laboratory or at UNC-Chapel Hill.

III. Select Agent Authorization

Authorization is Select Agent-specific. The University must seek separate authorization for each Select Agent they plan to work with.

Authorization requires:

• Approved Safety Protocols: Select Agent Authorized Users must have an approved Laboratory Safety Plan and Biosafety Level (BSL)-3 Laboratory Standard Operating Procedure (SOP) that describes the facilities, equipment, procedures, and security for safely handling these Select Agents. The Laboratory Safety Plan should document the following:
  • the individual Select Agents and the type of work being done;
  • safety procedures appropriate for work with these Select Agents, including access control, employee safety, and laboratory security; and
  • Select Agent destruction and disposal procedures.
• Safe and Appropriate Facilities: Select Agent Laboratories must meet the applicable standards in the current edition of Biosafety in Microbiological and Biomedical Laboratories (BMBL).
• Adequate agent, laboratory, building and cyber security: Select Agent Laboratories must meet strict security requirements to prevent access from unauthorized persons. Security procedures are detailed in UNC-Chapel Hill’s Security Plan. This plan is a secure document and will only be provided to registered Select Agent Workers.
• Compliance with UNC-Chapel Hill safety policies and procedures: In addition to legal requirements, Select Agent Workers must comply with UNC-Chapel Hill safety policies and procedures found in the EHS Laboratory Safety and Biological Safety Manuals, applicable standards in Biosafety in Microbiological and Biomedical Laboratories, training requirements, annual medical surveillance and procedures described in the Laboratory Standard Operating Procedure.
• Compliance with suitability assessments: Select Agent Workers must comply with pre-access suitability, ongoing suitability, self and peer reporting requirements to remain in the Select Agent program.
• Compliance of Select Agent Workers: The Select Agent Authorized User is responsible for the conduct of all Select Agent Workers who have access to the Select Agent under the Select Agent Authorized User's authorization.
• SRA: Persons may access a Select Agent or Toxin only after the CDC and the FBI have approved their SRA. Students, staff, visiting scientists or faculty (including the PI) who may ship, transport, access or possess a Select Agent must obtain an FBI SRA prior to gaining access to a Select Agent. Following the FBI SRA, the individual will receive authorization from the RO/ARO for access to the Select Agent Laboratory.

An unresolved security breach, a serious variance identified by an EHS safety survey or noncompliance with other UNC-Chapel Hill safety and security policies and procedures may result in the suspension of Select Agent authorization, confiscation of the Select Agent or Toxin, or denial of access to the Select Agent Laboratory until the matter is resolved.

IV. Requirements for Select Agent Workers

Only an SRA-approved Select Agent Worker may ship, transport, or have unescorted access to a Select Agent or Toxin. A Select Agent Worker is a student, staff member, visiting scientist, or faculty member (including the PI) who has:

• Met minimal education and experience requirements: Individuals may not have access to Select Agents or Toxins unless they have the following minimal education and experience:
  • A bachelor’s degree and/or training and experience to handle such Select Agents and Toxins. PI and EHS determine final approval for entry.
  • Training specific for Select Agent Laboratory. This currently includes a tour of the research laboratories by a qualified lab member and reviewing the following:
    • Laboratory Safety Plan,
    • Laboratory SOP,
    • BSP,
    • Security Plan, and
    • Incident Response Plan.
  • At least six (6) months of experience involving aseptic technique in a biological safety cabinet.
  • At least six (6) months of experience with applicable techniques (e.g., plaque assay, cell culture infections, centrifugation, etc.)
• Been designated for Select Agent access by the Select Agent Authorized User: Honest, reliable, and conscientious workers represent the foundation of an effective security program. The SRA is retrospective, limited and does not obviate the need for exercising good judgment in selecting honest, reliable, and conscientious workers. Extra care should be taken when selecting Select Agent Workers and authorizing access. The selection process should include others so that a consensus judgment is made. References must be checked. The Select Agent Authorized User, or their designated SRA-approved co-PI, are responsible for notifying the RO of any new faculty, staff, students, visiting scholars, or other individuals who wish to apply for access to a Select Agent.
• Obtained an SRA: Persons may access a Select Agent or Toxin only after the CDC and the FBI have approved their SRA. Anyone, including visitors, who have the freedom or ability to obtain and make use of a Select Agent or Toxin, must be approved. To obtain an SRA:
  1. EHS will provide the employee with a Unique Identifying Number (UIN).
  2. The employee will complete the FBI's "Bioterrorism Security Risk Assessment Form" (FD-961).
  3. The RO must review and sign the completed FD-961.
  4. The employee will take the completed and signed FD-961 to UNC-Chapel Hill Police and get two (2) sets of fingerprint cards completed.
  5. EHS will mail the completed FD-961 and the two sets of fingerprint cards to the FBI.
• Obtained a pre-assessment Personnel Suitability: Individuals that need access to Tier 1 BSAT, must complete a pre-access Personnel Suitability interview with the RO and are subject to UNC-Chapel Hill’s ongoing Personnel Suitability assessment program.
• Satisfied security and safety training requirements: This training will ensure that all Select Agent Workers understand security requirements and are trained and equipped to follow established procedures. EHS will provide this training and retain training records.
• Met all other applicable UNC-Chapel Hill training, occupational health and EHS requirements: These requirements include attending UNC-Chapel Hill Laboratory Safety Training and compliance with EHS policies and procedures. Other requirements may apply depending on the particular risks associated with the work to be performed.

V. Required Plans and SOPs

A. Biosafety Plan

The BSP is commensurate with the risk of the Select Agent or Toxin, given its intended use identified by DHHS under Title 42, Part 73 of the Code of Federal Regulations (42 CFR 73) at UNC-Chapel Hill. The goal of UNC-Chapel Hill’s BSP is to describe BSAT biosafety and containment, including for any animals (including arthropods) or plants intentionally or accidentally exposed to or infected with Select Agents.

UNC-Chapel Hill’s BSP is intended for use as a guidance document for Select Agent Workers. The CDC Guidance document entitled Select Agents and Toxins Biosafety and Biocontainment Plan Guidance, the BMBL, and NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules were used as reference documents for preparing the plan.

A hard copy of the BSP is available at EHS and an electronic version is also available for Select Agent Workers to review. EHS and PIs review the BSP at least annually.

B. Incident Response Plan

This Incident Response Plan (IRP) addresses emergency and incident responses to prevent the theft, loss, or release of Select Agents and Toxins identified by DHHS under Title 42, Part 73 of the Code of Federal Regulations (42 CFR 73) at UNC-Chapel Hill. The goal of UNC-Chapel Hill’s IRP is to preserve the safety and security of the University’s staff, emergency responders, the public, and the environment.

UNC-Chapel Hill’s IRP is intended for use as a guidance document for Select Agent and emergency personnel responding to incidents involving UNC-Chapel Hill Select Agent Laboratories. The CDC Guidance document entitled FSAP Guidance-IRP was used as a reference document for preparing the plan. UNC-Chapel Hill’s IRP is based upon a site-specific Risk Assessment.

This plan is coordinated with the UNC-Chapel Hill Emergency Plan. A hard copy is available at EHS and an electronic version is also available for Select Agent Workers to review. EHS and PIs review the IRP at least annually.

C. Security Plan

The Security Plan addresses the safety, security, and compliance of Select Agents and toxins identified by DHHS under Title 42, Part 73 of the Code of Federal Regulations (42 CFR 73) at UNC-Chapel Hill. The goal of UNC-Chapel Hill’s Security Plan is to safeguard Select Agents or Toxins against unauthorized access, theft, loss, or release.

UNC-Chapel Hill’s Security Plan is intended for use as a guidance document for Select Agent Workers. The CDC Guidance document entitled Security Plan Guidance was used as a reference document for preparing the plan. UNC-Chapel Hill’s Security plan is based upon a site-specific Risk Assessment.

A hard copy of the Security Plan is available at Environment, Health and Safety and an electronic version is also available for Select Agent Workers to review. EHS, PIs, and the Chief of UNC-Chapel Hill Police review the Security Plan at least annually.

D. BSL-3 Laboratory Standard Operating Procedures

Each Select Agent Laboratory must have a lab-specific SOP. The SOP is required to have hazard information, facility descriptions, entry and training requirements, medical surveillance requirements, daily operating procedures, entry and exit procedures and information regarding lab equipment. The PI/Lab Manager, EHS, and the IBC review the SOP at least annually.

VI. Required Documentation

Select Agent records are maintained by the Select Agent Authorized User as well as centrally at EHS and within the University’s Select Agent Tracking System. All records must be maintained for a minimum of three (3) years.

• Inventory Records: Each Select Agent Authorized User must maintain an accurate, current inventory of each Select Agent held in storage and implement effective inventory control procedures. The Security Plan describes the Select Agent Inventory and Tracking System used to maintain these records.
• List of approved individuals: EHS maintains a current list of all SRA-approved personnel.
• Records of access into the Select Agent Laboratory: For SRA-approved individuals, access to and exit from a Select Agent Laboratory is recorded and maintained by the keycard access system for that area. A logbook is used to record entry to Select Agent Laboratories by visitors and other individuals who are not SRA-approved. The logbook is maintained by the Select Agent Laboratory and reviewed by EHS during the annual laboratory inspection.
• Records of internal inspections: EHS will maintain inspection records and laboratory responses to inspections.
• Transfer Documents: EHS maintains Form 2 and intra-entity transfer documents.
• Training records: EHS will maintain training records.
• Safety and security incident reports: EHS and the UNC-Chapel Hill Police will maintain safety and security incident reports.

VII. Annual Inspections

UNC-Chapel Hill Police and EHS will perform an annual security inspection of buildings and laboratories where Select Agents are in use. UNC-Chapel Hill Police and EHS will jointly review Select Agent, laboratory, and building security.

EHS will verify the accuracy and authenticity of the laboratory’s entry logs (i.e., keycard system reports and visitor logbook) by verifying that the listed Select Agent Workers, visitors and other personnel had an approved SRA and/or other authorizations at the time they accessed the area where Select Agents are used or stored.

EHS will perform an annual inspection that reviews:

• safety practices,
• personal protective equipment,
• training compliance,
• facility operational parameters,
• biological safety cabinet and HEPA filter certifications,
• engineering controls, and
• compliance with the occupational health program.

EHS will verify the accuracy and authenticity of Select Agent inventory records by conducting a physical inventory yearly.

VIII. Permissible Toxin Amounts (HHS Toxins [§73.3(d)(7)])

Except as required in § 73.16(l), the following toxins are not regulated, if the aggregate amount of toxin under the control of a principal investigator, treating physician or veterinarian, or commercial manufacturer or distributor does not, at any time, exceed the following amounts indicated in the table below

A. Due Diligence Provision: [§ 73.3(d)(7)(i)]

The Federal Select Agent Program developed this provision because there is always a concern that someone might stockpile toxins by receiving multiple orders below the excluded amount. In order to address this issue, the Federal Select Agent Program has put in place the "toxin due diligence" provision.

This provision requires a person transferring toxins in amounts which would otherwise be excluded from the provisions to use due diligence and document the identification of the recipient and the legitimate need (e.g., prophylactic, protective, bona fide research, or other peaceful purpose) claimed by the recipient to use such toxin. Information to be documented includes, but is not limited to, the recipient identity information, including the recipient’s name, institution name, address, telephone number and email address; name of the toxin and the total amount transferred; and the legitimate need claimed by the recipient.

Notwithstanding the provisions of paragraph (d) in the regulations, the HHS Secretary retains the authority to, without prior notification, inspect and copy or request the submission of the due diligence documentation to the CDC.

UNC-Chapel Hill has implemented this provision by asking the PI the following questions on the Laboratory Safety Plan:

• I will require the recipient to complete and submit to me documentation stating their intended use of the toxins, information pertinent to the person requesting and using the toxins includes the individual’s name, institution name, address, telephone number, and email address.
• I will document my knowledge of the recipient’s legitimate need for the toxins pertinent to the person requesting and using the toxins. Information pertinent to the person requesting and using the toxins includes the individual’s name, institution name, address, telephone number and email.
• Those toxins that are stored and/or manipulated in our laboratory do not fall under the Select Agent regulations.

When completed, the Laboratory Safety Plan's “Due Diligence” section is submitted online to the Biosafety Section for review to ensure PIs are complying with the regulations.

Through the Laboratory Safety Plan, the Biosafety Section tracks which researchers have toxins and can run a report for inspection purposes.

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