2008–2015 SA Grams

On August 28, 2104, the White House released the Holdren-Monaco Memorandum and a statement of support from the White House calling for enhanced biosafety/biosecurity measures. The memorandum acknowledges the importance of life science research for combating natural disease outbreaks and deliberate acts of bioterrorism, but stresses the U.S. Government’s responsibility to ensure infectious disease research is conducted safely and securely.

Recent reports of lapses in biosafety practices involving Federal laboratories have served to remind us of the importance of constant vigilance over our implementation of biosafety standards. As a measure toward preventing future lapses as well as promoting stewardship of the life sciences and biosafety awareness across Federal entities, the US Government is urging all state, public, university or private laboratories to do the same at the local level during the month of September. Promoting safe and secure practices in laboratory facilities protects workers and the public, and prevents potential damage to human, animal, and plant health.

The Holdren-Monaco memo calls on Federal agencies to take the following immediate actions:

1. Conduct a comprehensive review of current biosafety and biosecurity protocols to ensure adequacy and appropriateness for today’s infectious disease research
2. Develop and implement plans for sustained inventory monitoring
3. Initiate an immediate sweep of their facilities to identify biological select agents and toxins are not located in unregistered areas.
4. Encourage extramural facilities which receive United States Government funding to hold similar events

Additional guidance on biosafety and biosecurity as well as pertinent regulations can be found at: http://www.phe.gov/s3/faqs/Pages/biosafety.aspxexternal icon and http://www.phe.gov/s3/legal/Pages/laws.aspxexternal icon.

The Federal Select Agent Program encourages all entities to highlight the importance of the requirements and activities that are already part and parcel of a robust biosafety program. We believe that it is also an opportunity for entities to further optimize biosafety oversight and strengthen their institutional safety culture by conducting activities that may include, but are not limited to:

• Conducting comprehensive reviews of current biosafety and biosecurity protocols and procedures to ensure they are adequate for today’s research;
• Review procedures for biosafety, biosecurity, and inventory management;
• Identifying and rectifying any gaps in the institutional biosafety and biosecurity oversight programs
• Sweep areas used to store human, animal or plant infectious agents or toxins, especially areas containing historical collections to ensure that no unregistered select agents and toxins are present;
• Conduct facility biosafety/biocontainment training sessions; and
• Complete safety assessments or mock emergency response activities.

As of August 1, 2014, the Federal Bureau of Investigation, Criminal Justice Information Services Division (CJIS) will no longer accept the form FD-961 that does not include the Entity Application Number for question #1 in Section 1. The Entity Application Number (referred to as “entity ID” (i.e., AGRxxxxxx or CDCxxxxxx) is included in letters used by the Federal Select Agent Program to issue a unique identifying number for an individual identified by an entity as requiring a security risk assessment. You may also ask your file manager for your entity application number. If you are unsure of who your file manager is, please contact the Federal Select Agent Program: APHIS/AgSAS, 301-851-2070 or CDC/DSAT, 404-718-2000. If you have any questions regarding the FD-961 form, please contact CJIS at 304-625-4900.

This email is to notify you that the Federal Bureau of Investigation, Criminal Justice Information Services Division (CJIS) does not accept FD-961 form with digital signatures. If you have any questions regarding the FD-961 form, please contact CJIS at 304-625-4900.

The Federal Select Agent Program is no longer requiring that the Responsible Official, Alternate Responsible Official(s), and any individual who owns or controls the entity, unless otherwise exempted, to undergo a security risk assessment at the time of the entity?s registration renewal, as long as each individual has a security risk assessment performed prior to the expiration date of your registration. In addition, a completed APHIS/CDC Form 1 must now be submitted at least 30 days prior to the scheduled renewal inspection or 90 days prior to the entity’s expiration date, whichever occurs first. The self-certification form is no longer required to be completed.

The Federal Select Agent Program (FSAP) has amended the select agent regulations so regulated entities that maintain shipping and receiving facilities, and have procedures that are able to maintain select agent and toxin anonymity in shipping/receiving facilities, i.e., preserving “lost in the crowd,” will not be required to register these areas if packages containing select agents or toxins will temporarily be stored in these areas awaiting transportation pickup. For entities preserving the “lost in the crowd” concept during shipping and receiving, the select agent regulatory oversight for recipients begins when a select agent or toxin package arrives at its ultimate destination for unpacking by an individual approved for access by the Department of Health and Human Services (HHS) Secretary or Animal and Plant Health Inspection Service (APHIS) Administrator. Select agent and toxin oversight for senders covers all use of a select agent and toxin up to the time that the materials are packaged for shipment, in compliance with Department of Transportation (DOT) hazardous materials regulations, by an individual approved for access by the HHS Secretary or APHIS Administrator. If packages are labeled as containing “Suspected Category A infectious substances” and temporarily stored in the shipping/receiving area, there is no need to develop and implement security practices (e.g., securing packages, registering the shipping/receiving area, and meeting Tier 1 requirements) for the area as the “lost in the crowd” concept is being preserved.

The FSAP approves and DOT recommends the use of “lost in the crowd” for all shipments of a select agent and toxin. To comply with this approach, “suspected Category A infectious substance” can be used as the technical name on the Shipper’s Declaration of Dangerous Goods in-lieu of identifying the select agent in the technical name, such as by listing the specific genus and species. Note: the technical name is included in parenthesis after the proper shipping name in the “Proper Shipping Name” section of the form. This approach will assist in maintaining anonymity for select agent and toxin packages during transit and avert additional security risks for couriers. Also, the technical name should not be placed on the package itself; instead the area for the technical name should be left blank.

In collaboration with DOT, the FSAP has developed guidance for the regulated community on the packaging and shipping of select agents and toxins. This guidance is available here and includes information on all applicable domestic and international shipping regulations.

The Federal Select Agent Program would like to make you aware of our policy for verifying Federal Select Agent Program Inspectors and an entity’s request to sign a confidentially agreement. The Federal Select Agent Program Inspectors have statutory authority (Public Health Security and Bioterrorism Preparedness and Response Act, 2002) to enter an entity in possession of biological select agents in toxins to perform inspections related to compliance with the HHS and USDA Select Agent Regulations (42 CFR Part 73, 9 CFR Part 121, and 7 CFR Part 331).

A Federal Select Agent Program Inspector may show an entity his/her official government badge. The official government badge consists of the employee’s name, picture of the employee, the individual’s personal identifier number, and the government agency that the employee is affiliated. All Federal Select Agent Program Inspectors have undergone appropriate Federal background investigations and adhere to Federal Select Agent Program policy’s for safeguarding select agent information.

The Federal Select Agent Program Inspector is not allowed to give the entity his/her official government badge in exchange for the entity’s identification badge. In addition, the entity is not allowed to copy the badge. The Federal Select Agent Program Inspector will not provide the entity with any personal identification such as driver’s license, social security card, etc. The entity may request for the Federal Select Agent Program to provide the entity with an “Inspector Verification” letter prior to the arrival of the inspectors. However, a request for an “Inspector Verification” letter, or the absence of an “Inspector Verification” letter may not be used as grounds for delaying the start of an inspection.

The Federal Select Agent Program Inspector is not authorized to and may not sign a confidentiality agreement connected in any way to their duties as an inspector for the Federal Select Agent Program.

• BSL-3 D9: “The laboratory shall be designed such that under failure conditions the airflow will not be reversed.”
• ABSL-3 D6: “The ABSL-3 animal facility shall be designed such that under failure conditions the airflow will not be reversed.”
• BSL-3 D15: “The BSL-3 facility design, operational parameters and procedures must be verified and documented prior to operation. Facilities must be re-verified and documented at least annually.”
• ABSL-3 D14: “The ABSL-3 facility design and operational procedures must be documented. The facility must be tested to verify that the design and operational parameters have been met prior to use. Facilities should be re-verified at least annually against these procedures as modified by operational experience.”

The Federal Select Agent Program Policy is based on the above BMBL Standards as currently published and is subject to change. Current policy:

I. BSL-3/ABSL-3 Initial HVAC Verification

Initial HVAC design verification must be performed and documented by someone with experience and expertise with the HVAC system prior to operation. This initial HVAC design verification ensures that secondary containment is maintained under failure conditions to prevent possible exposure of personnel outside the containment boundary. After HVAC verification is initially documented, the testing need not be repeated, providing no major changes have been made to, or major problems noted with, the HVAC system. See Section II below for details on major changes and major problems which may require repeat HVAC verification.

Documentation must be provided of verification of HVAC design functionality under failure conditions. The failure conditions for verification include:

1. Mechanical failure of exhaust fan or fan component(s):
   • If redundant fans are present, the ability to transition to the alternate fan without reversal of air flow from potentially contaminated laboratory space into “clean” areas surrounding the laboratory must be verified.
   • If no redundancy is present in the laboratory HVAC system, the capacity to transition from sustained inward air flow into the laboratory to a “static” condition, i.e., no air flow out of the laboratory must be verified.
2. Simultaneous power failure supporting supply and exhaust fan components:
   • If emergency power supply is available for the laboratory HVAC system, the ability to transition from “normal” power to the backup system without a reversal of air flow from the laboratory should be verified.
   • If no backup power supply is available, the ability of the HVAC system to transition to a “static” condition, i.e., no outward air flow, should be verified.
3. Return from power failure to “normal” operating conditions:
   • If emergency power supply is available, it should be verified that the ability exists to transition from backup power to normal power without a reversal of air flow from the laboratory.
   • If no backup power supply is available, the ability of the HVAC system to return to normal operating conditions, without a reversal of air flow from laboratory spaces to clean areas surrounding the laboratory should be verified.

II. BSL-3/ABSL-3 Repeat HVAC Verification

Once the BSL-3/ABSL-3 HVAC verification has been completed and approved by CDC/DSAT or APHIS/ASAP, HVAC failure conditions testing need not be repeated, providing there have been no major changes made to the HVAC system and no major problems noted with HVAC performance. Examples of major changes to the HVAC system which may require re-verification of HVAC design functionality under failure conditions by someone with experience and expertise with the system include: replacement of exhaust or supply fans that serve the BSL-3/ABSL-3 containment areas, replacement of ductwork valves or dampers that serve these areas, replacement or repair of HVAC system control wiring, building automation system logic programming changes, structural changes to the BSL-3/ABSL-3 rooms, or addition or removal of hard-ducted BSCs or fume hoods. Examples of major problems with HVAC performance that may require re-verification of HVAC design functionality under failure conditions include: frequent failures of the HVAC system, supply-exhaust interlocking system failure, observation that directional air flow is reversed under normal conditions, observation that HVAC alarms are not working, or that any BSCs with an HVAC connection are not working properly.

III. Acceptance Criteria for HVAC Verification

The documentation provided must demonstrate that under exhaust fan or normal power failure conditions, or during normal power start-up, there is no reversal of air which originates within the BSL-3/ABSL-3 laboratory or vivarium room that travels all of the way outside the containment boundary. A facility may be considered to pass the HVAC verification tests as long as laboratory air does not exit the containment barrier of the facility. The BSL-3 anteroom is considered to be within the containment envelope. A positive pressure excursion is not necessarily an airflow reversal; if a brief, weak positive pressure excursion is noted, a repeat test may be performed with airflow observation using an airflow indicator such as a smokestick, or dry ice in a container of water, at the base of the closed laboratory door to confirm whether airflow reversal is occurring.

IV. BSL-3/ABSL-3 Initial Facility Verification and Annual Re-verification

In addition to initial HVAC verification and re-verification as described above, the following are the minimum facility verification requirements that an entity is expected to perform and document initially for a BSL-3 or ABSL-3 laboratory and again at least annually. Some entities may choose to perform additional facility verification beside what is listed below.

1. The means of detecting air flow (tell tale, magnehelic or digital gauge, Baulin-Tube®, etc.) has been confirmed to accurately reflect observed air flow. It is recommended, but not required, that digital or magnehelic gauges be calibrated annually.
2. Inward directional airflow has been confirmed by observation for the laboratory.
3. Decontamination systems (autoclave, room decontamination systems, digesters, liquid effluent systems, etc.) have been confirmed to be operating correctly.
4. If a Building Automation System has the capacity to monitor and record performance measurements, e.g., differential pressures, the entity is encouraged to capture and store data from potential failure events, drills, etc. This information may provide verification of system performance. In addition, any programmed BAS alarms should be verified for proper functioning.
5. All alarms (fire, air flow, security, etc.) have been checked and are functioning according to established specifications.
6. Laboratory HVAC HEPA filters, if present, have been certified annually.
7. Exhaust fan motors have been checked and routine maintenance conducted.
8. The laboratory has been checked for unsealed penetrations, cracks, breaks, etc. and these have been repaired if present.
9. All biological safety cabinets have been certified annually.
10. Seals on centrifuges, Class III cabinets, gloves on Class III cabinets, etc. have been checked and replaced if required.
11. Drench showers, eye wash stations, and hands free sinks have been confirmed to be operating properly.

Once an animal is injected with or exposed to a select toxin, does the animal need to be treated as a select toxin and housed in registered space?

No. Once an animal has been injected with or exposed to (for example, by inhalation, dermal absorption, or ingestion) a select toxin, the animal would not be considered a “select toxin” and would not need to be housed in a registered space.

Until the select toxin is injected into or exposed to the animal, the select toxin would be regulated under the Select Agent Regulations. This would include storage or use of the material (e.g., injection or exposure procedure). If select toxin is stored or used in the same area as the injected or exposed animal, the space will need to be listed on your entity’s approved certificate of registration.

The room where the injection or exposure procedures occur may be assessed using laboratory biosafety level criteria instead of animal biosafety level criteria.

Note: The Federal requirements to register with the select agent program apply at any time the aggregate amount of a select toxin under the control of a principal investigator, treating physician or veterinarian, or commercial manufacturer or distributor exceeds the aggregate amounts specified (See 42 CFR §§ 73.3). For Botulinum neurotoxins, if the toxin preparation contains Botulinum neurotoxin producing strains of Clostridium, the animals will need to be treated as a select agent.

This FAQ is available at www.selectagents.gov under the general FAQ tab.

The Centers for Disease Control and Prevention (CDC) and the Animal and Plant Health Inspection Service (APHIS) Select Agent Programs are providing clarification related to questions that we have received regarding hand delivery of packages containing select agents and toxins. The Select Agent Programs have developed and posted the below frequently asked questions on the Select Agent Program website at: http://www.selectagent.gov/FAQ_TransferForm2.html.

Are we required to use a commercial carrier for the domestic shipment within the United States of select agent shipments or can we hand deliver a package containing select agents or toxins to a registered recipient?

The select agent regulations do not require the use of a commercial carrier for select agent shipments. However, even if an entity chooses to hand deliver a package containing a select agent or toxin to another registered entity it must still comply with section 16 (Transfers) and the transfer must be authorized by Select Agent Program. To initiate the transfer authorization, a CDC/APHIS Form 2 must be completed and sent to the Select Agent Program. In addition, the individual who is hand carrying the package must be SRA approved. The entity also remains responsible for ensuring that all local, state or federal transportation requirements for the transportation of hazardous materials are followed. [Note: If the entity moves the select agent or toxin “in commerce” using a common, contract, or private carriers, U.S. Department of Transportation hazardous materials regulations will apply.] The entity must ensure that adequate precautions are taken to prevent a theft, loss or release of the select agents and toxins. In addition, for animal or plant pathogens, interstate and certain intrastate movements will require a valid APHIS permit.

Are we required to use a commercial carrier for importations of select agent shipments into the United States or can we hand deliver a package containing select agents or toxins to a registered recipient?

Yes. The Select Agent Program, in order to ensure the security and safety of select agents, will not approve the importation of select agent material unless it is to be transported into the United States via a commercial carrier. An exception is for materials regulated under the U.S. Department of Agriculture’s Plant Protection and Quarantine regulations (PPQ; 7 CFR Part 331) under certain conditions as described below. These materials may be hand-carried into the U.S. under the following conditions:

1. A request to hand-carry must be in writing including detailed reasons for the need to hand carry vs. commercial carrier, person’s passport number, travel locations, date and times of itinerary; date, time, airline, arriving flight number, and first location of U.S.-landing must be supplied and in advance of the proposed foreign travel. The need for hand-carrying is considered extraordinary (i.e. not the convenience of the person.
2. The requestor must be a Federal employee who is a United States resident, be FSAP-approved, and have at least a secret-level clearance.
3. The requester must hold a valid permit (PPQ Form 526) to import the select agents that are to be hand-carried. Secure packaging of the biological material is stated in the permit conditions. Additional packaging or carrying conditions are on a case-by-case basis.
4. Agriculture Select Agent Program writes a courier letter to the Custom and Border Patrol (CBP) workstation at the first U.S. port of entry. The letter details the individual, trip itinerary, the carrying of “biological material” (not the exact name) that is permitted by Animal and Plant Health Inspection Service (APHIS), the date, time, flight #, departing and arriving cities, the final destination of the person, and requests that CBP and Immigration expedite the individual through Customs as they are on official travel for the U.S. Government. This letter is sent through Department of Homeland Security (DHS), CBP channels for delivery to the workstation. The individual is required to carry a copy of this letter with their travel documents and to show it upon CBP request.
5. The individual must place imported select agent in the entity’s inventory and update the inventory records accordingly.
6. The individual must notify Agriculture Select Agent Program of the select agent arrival to the final destination within 24 hours of arrival.

The Centers for Disease Control and Prevention (CDC) and the Animal and Plant Health Inspection Service (APHIS) Select Agent Programs have established a confidential means for reporting safety and security issues associated with the possession, use and transfer of select agents and toxins. The Department of Health & Human Services, Office of Inspector General (OIG) maintains a hotline that allows individuals to anonymously report fraud, waste and abuse in all departmental programs. This hotline is now available to anonymously report safety or security issues related to select agents and toxins. When reporting these issues to OIG, please ensure that you indicate it is a “Select Agent Program” issue.

OIG Hotline contact information:

Voice: 1-800-HHS-TIPS (800-447-8477)
Fax: 1-800-223-8164
Email: HHSTips@oig.hhs.gov
Web: http://oig.hhs.gov/fraud/hotlineexternal icon
Mail:
Office of Inspector General
Department of Health & Human Services
Attn: Hotline
P.O. Box 23489
Washington, DC 20026

The OIG Hotline information will also be available at: http://www.selectagents.gov/index.html.

Beginning May 1, 2008, the Centers for Disease Control and Prevention, Division of Select Agents and Toxins (DSAT) will be inspecting entities using the nationally recognized biological safety standards in the 5th Edition of the Biosafety in Microbiological and Biomedical Laboratories (BMBL) instead of the 4th Edition. To assist entities in complying with the requirements of the select agent regulations, DSAT and the Animal and Plant Health Inspection Service (APHIS), Select Agent Program have posted the biosafety checklists that will be used in the inspections of your entity. In addition, a comparison matrix that discusses the changes between the 4th Edition and 5th Edition is also available. These documents can be viewed at: http://www.selectagents.gov/securitydoc.htm.

Currently, the BMBL 5th Edition is only available in electronic form on the Centers for Disease Control and Prevention web site at http://www.cdc.gov/od/ohs/biosfty/bmbl5/bmbl5toc.htm.