General questions about shipping and receiving

1. What is meant by an "unexpected shipment"?

   An "unexpected shipment" is when an entity receives a shipment of a select agent that it had neither requested nor coordinated for, and therefore was not expecting.

2. Do the select agent regulations require any physical measures (i.e., cages, safes) to secure shipments containing select agents or toxins prior to being picked up by a commercial carrier for delivery to the intended recipient?

   If the package containing select agents and toxins is labeled generically as "Category A infectious substance" and does not identify the package as containing a select agent or toxin, the package can be placed with other packages in the area the entity uses for shipment of materials.

3. Is "chain of custody" paperwork required to track a package containing select agents or toxins until the package is provided to the commercial carrier?

   If the package containing select agents and toxins is packaged by the laboratory and labeled generically as "Category A infectious substances" as required by the DOT regulations, the package can be placed with other packages in the area that the entity uses for shipment of materials and does not need to be accompanied by "chain of custody" paperwork.

   However, if the select agents and toxins are sent to another area for packaging and shipping, "chain of custody" paperwork is required to document transfer from the laboratory to the area where packaging occurs. The area where packaging occurs must be listed on the entity's certificate of registration and must meet all the requirements outlined in the select agent regulations as for other registered areas listed on the entity’s certificate of registration. If Tier 1 select agents and toxins will be packaged in the shipping and receiving area, it must meet all provisions associated with Tier 1 requirements. All individuals who will have access to Tier 1 select agents or toxins must also meet Tier 1 requirements and be enrolled in the entity’s suitability assessment program. The area will also be inspected to ensure the entity’s compliance with the select agent regulations.

4. Is the receiving entity required to use "chain of custody" paperwork to track a package containing select agents or toxins from the time it is received by the entity from a commercial shipper until the package is received by the intended recipient?

   No, the package will not be identified as containing select agents or toxins and will be considered "lost in the crowd" until received by the intended recipient or his/her designee. It should be noted that the package containing select agents and toxins is not considered "received" by the entity until the intended recipient takes possession of the package.

5. 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.

6. 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:

   • 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).
   • The requestor must be a Federal employee who is a United States resident, be SRA-approved, and have at least a secret-level clearance. 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. 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.
   • The individual must place imported select agent in the entity's inventory and update the inventory records accordingly.
   • The individual must notify Agriculture Select Agent Program of the select agent arrival to the final destination within 24 hours of arrival.

General questions about transferring a select agent or toxin

1. What is the purpose of an APHIS/CDC Form 2?

   You use an APHIS/CDC Form 2 to request authorization to transfer a select agent or toxin. It also provides documentation of the transfer. By regulation, an APHIS/CDC Form 2 must be completed for each transfer of select agent(s) or toxin(s) and maintained for three years.

2. Is a transfer authorization from APHIS or CDC needed for intra-entity transfers?

   No, but an intra-entity transfer is limited to those instances where a select agent or toxin is moved from one location within an entity to another (e.g., A Principal Investigator transferring part of his select agent inventory to another Principal Investigator from the same entity). The entity doing an intra-entity transfer must create a record of the intra-entity transfer that must include the following information: the select agent or toxin, quantity, date, sender, and recipient. By regulation, the record has to be maintained for a minimum of three years. If an entity does intra-entity transfers, its security plan must include a protocol for intra-entity transfers including chain-of-custody documents and provisions for safeguarding against theft, loss, or release. For more information regarding intra-entity transfers, refer to the "Security Guidance for Select Agent or Toxin Facilities" at http://www.selectagents.gov/guidance-securityfacility.html.

3. Our diagnostic laboratory, which is not listed on my entity's approved registration, would like to transfer the select agent that was identified in a clinical sample to a laboratory room listed on my entity’s approved certificate of registration. Does this require an approved APHIS/CDC Form 2?

   Yes, the transfer of a select agent from an area not listed on your entity’s approved registration to a laboratory room listed on your entity’s approved registration is NOT considered an intra-entity transfer. Intra-entity transfers involve the transfer of select agents from one registered location to another registered location covered by the same certificate of registration.

4. Is a transfer authorization from AgSAS or DSAT needed to transfer toxins in a quantity below the regulated amounts?

   No, a transfer authorization would not be needed for toxins under the control of a principal investigator, treating physician or veterinarian, or commercial manufacturer or distributor if the aggregate amount does not exceed the following amounts: Abrin 1000 mg, Botulinum neurotoxin 1 mg, Conotoxins (Short, paralytic alpha conotoxins) 100 mg, Diacetoxyscirpenol 10,000 mg, Ricin 1000 mg, Saxitoxin 500 mg, Staphylcoccal enterotoxin (A, B, C, D, E subtypes) 100 mg, T-2 toxin 10,000 mg, and Tetrodotoxin 500 mg.  The toxin can only be transferred after the transferor uses due diligence and documents 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 e-mail address; name of the toxin and the total amount transferred; and the legitimate need claimed by the recipient.  The entity must also report to CDC if they detect a known or suspected violation of Federal law or become aware of suspicious activity related to a select toxin.

5. Is a transfer authorization from AgSAS or DSAT needed to transfer attenuated strains of select agents that have been excluded by AgSAS or DSAT from the Select Agent Regulations?

   No, the regulations establish a procedure by which the Federal Select Agent Program may exclude from the requirements of the select agent regulations an attenuated strain of a select biological agent or toxin determined by the Federal Select Agent Program not to pose a severe threat to public health and safety, animal and plant health, or animal and plant products. The list of approved attenuated strains can be found on the Federal Select Agent Program website at www.selectagents.gov/SelectAgentsandToxinsExclusions.html. If an attenuated strain of a select biological agent or toxin is not listed at www.selectagents.gov/SelectAgentsandToxinsExclusions.html, the agent or toxin is still considered a select agent or toxin and would need a transfer authorization from the Federal Select Agent Program.

6. How do I submit a transfer request (APHIS/CDC Form 2)?

   You may submit your transfer request to AgSAS or DSAT by mail, fax or email:

   Animal and Plant Health Inspection Service Agriculture Select Agent Services 4700 River Road Unit 2, Mailstop 22, Cubicle 1A07 Riverdale, MD 20737 FAX: 301-734-3652 E-mail: AgSAS@aphis.usda.gov

   Centers for Disease Control and Prevention Division of Select Agents and Toxins 1600 Clifton Road NE, Mailstop A-46 Atlanta, GA 30329 FAX: 404-471-8468 Email: cdcform2@cdc.gov

   
   
7. Once submitted, when can I expect a decision regarding my transfer request?

   A written decision from AgSAS or DSAT is usually provided within 72 hours of receipt of the request. However, please note that an APHIS/CDC Form 2 with incomplete or inaccurate information may delay a decision concerning your request.

8. How long is a transfer authorization from the Federal Select Agent Program valid?

   Approval of the transfer of a select agent and toxin is valid for 30 days from the date of authorization. This means that the transfer of the select agent or toxin must be completed before expiration of the 30 day period. Additionally, approval of a transfer becomes void should there be a change in any of the conditions upon which the approval was based (e.g., change in the certificate of registration for the sender or recipient or change in the application for transfer). Each transfer authorization number is valid for only one transfer of select agents or toxins during the 30 day period.

9. We received authorization to transfer select agents to a registered entity. Can we ship multiple packages using the same transfer authorization number over the next 30 days?

   It depends. Each transfer authorization number is valid for only one transfer of select agents or toxins during the 30-day period. Therefore, multiple shipments occurring on different days would require separate authorizations from the Federal Select Agent Program. Large shipments that include multiple packages of select agents shipped on the same day can be shipped under the same transfer authorization number. Tracking information for each package of the large shipment needs to be provided on the APHIS/CDC Form 2.

10. Is a non-registered entity allowed to receive select agents?

    No, within the United States (U.S.), only entities that are registered with the Federal Select Agent Program are allowed to receive agents that have been identified as select agents. This includes the importation of select agents from outside the U.S.

11. What are the requirements for importation of a select agent or toxin into the United States?

    The importation of the select agent or toxin has been authorized in accordance with 42 CFR 73.16 or 9 CFR 121.16.

12. Is a transfer authorization from the Federal Select Agent Program required to export a select agent or toxin to a foreign country outside of the United States?

    No, however; the Department of Commerce regulates the exportation of a wide variety of etiologic agents of human, plant and animal disease and may require an export license. Information may be obtained by calling the DOC Bureau of Export Administration at (202) 482-4811, or at: http://www.access.gpo.gov/bis/index.html or http://www.bis.doc.gov/.

13. Is a transfer authorization from Federal Select Agent Program needed to transfer a presumptive select agent or toxin identified in a clinical/diagnostic laboratory specimen?

    Anyone may send a presumptive select agent to a reference laboratory for confirmation without a transfer authorization from Federal Select Agent Program. However, after identity of the select agent or toxin is confirmed, a non-registered entity would be required to either destroy the specimen (diagnostic sample containing the isolate) or any isolates, or transfer it to an entity registered for that select agent or toxin. That transfer must first be authorized by either Federal Select Agent Program. To initiate the transfer process, contact a registered entity to arrange for transfer of your sample. If you need assistance locating a registered entity, contact AgSAS ( phone: 301-851-3300 (option 3); fax: 301-734-3652) or DSAT (phone: 404-718-2000; fax: 404-471-8468). For further guidance regarding reporting requirements for the identification of a select agent or toxin contained in a clinical/diagnostic laboratory specimen, please refer to: http://www.selectagents.gov/form4.html.

14. Is a transfer authorization from Federal Select Agent Program needed to transfer a select agent or toxin that is contained in a specimen for proficiency testing?

    No, a sponsor/sender may send a select agent or toxin that is contained in a specimen for proficiency testing to a recipient without obtaining prior authorization from the Federal Select Agent Program provided that, at least seven calendar days prior to the transfer, the sponsor/sender send the Federal Select Agent Program a written report that includes the select agent or toxin to be transferred and the name and address of the recipient. For further guidance on reporting the identification of a select agent or toxin contained in a proficiency test, please refer to: http://www.selectagents.gov/form4.html.

15. What should I do if a delivery exception occurs?

    A delivery exception occurs when a shipment is held by the carrier or returned to the shipper due to inadequate paperwork. If this occurs, please notify the Federal Select Agent Program and the recipient entity immediately. The notification should include the following:

    • New tracking number(s)
    • The reason and needed action associated with the delivery exception
    • Expected new date of arrival

    Note: A copy of an updated Section 2 of APHIS/CDC Form 2 must be submitted to the Federal Select Agent Program and the recipient prior to delivery. Please ensure blocks #34 and #37 are updated accordingly.

    Once the delivery exception package is delivered, the recipient must:

    • Ensure that the expected shipment was properly packaged, labeled, and shipped in accordance with all federal regulations.
    • Ensure that the shipment information (example: updated tracking number(s)) matches the information documented in the updated Section 2 of the APHIS/CDC Form 2.

    
    
16. Is a transfer authorization from the Federal Select Agent Program required to transfer select agents or toxins identified from clinical/diagnostic specimens being sent for susceptibility testing?

    Yes, prior authorization from the Federal Select Agent Program is required for the transfer of the identified select agent(s) or toxin(s) being sent for susceptibility testing.

    Additional information on reporting the identification of a select agents and toxins is available at: http://www.selectagents.gov/faq-reporting.html.

General questions about completing the APHIS/CDC Form 2

1. Can the Alternate Responsible Official (ARO) sign the APHIS/CDC Form 2 if the Responsible Official (RO) is unavailable?

   Yes. The ARO can sign the APHIS/CDC Form 2 if he or she is acting as the RO in the RO's absence. However, the RO's name and contact information should be entered in Section A, Box 9 of the form even if the ARO signs the form.

2. What do I put in Block 20 if I am not registered with Federal Select Agent Program?

   For non-registered entities, it is acceptable to list the facility director or laboratory manager.

3. What address should be specified under Section A (Recipient Information) and Section B (Sender Information)?

   For registered entities, the address specified should be the entity's complete address, exactly as it appears on their current certificate of registration. For non-registered entities, please provide the complete, legal address of your entity. Please do not provide a P.O. Box.

4. After a transfer authorization is received from Federal Select Agent Program, what is required of the sender that wants to ship a select agent or toxin?

   The sender must:

   • Notify the Recipient of the expected shipment and document this notification in Section 2 of the form.
   • Ensure the material is properly packaged, labeled, and shipped in accordance with all federal regulations.
   • Ensure that the individual's information and description of the package are documented in Section 2 of the form.
   • Send AgSAS or DSAT a copy of the completed APHIS/CDC Form 2 (Sections 1 and 2) prior to shipment and include a copy with the select agent package.
   • In the case of an import shipment, the sending entity should notify the recipient entity with all relevant shipping information including the expected shipment date arrival, which the recipient entity should then forward to AgSAS/DSAT.

   
   
5. What does the Recipient need to do upon receipt of the select agent shipment?
   • First, confirm that all the select agents and toxins listed on Section 2 of the form were received. Document any discrepancies and notify the sender and AgSAS or DSAT. If it is determined that there was a theft or loss during packaging or in transit, immediately contact AgSAS (phone: 301-851-3300 (option 3); fax: 301-734-3652) or DSAT (phone: 404-718-2000; fax: 404-471-8468) and submit APHIS/CDC Form 3 "Report of Theft, Loss or Release of Select Agents and Toxins." More information about reporting a theft or loss of a select agent or toxin is available at: www.selectagents.gov/form3.html. If it is determined that the discrepancy is due to an administrative error, send an explanation of the error and a corrected APHIS/CDC Form 2 to AgSAS or DSAT. Please note that all records associated with a transfer should be kept for three years.
   • Inspect the package to verify that it is not damaged or leaking and that the material was packaged, labeled and shipped in accordance with federal regulations. If the package is received damaged or leaking to the extent that a release of the select agent or toxin may have occurred, immediately contact AgSAS (phone: 301-851-3300 (option 3); fax: 301-734-3652) or DSAT (phone: 404-718-2000; fax: 404-471-8468) and submit APHIS/CDC Form 3 "Report of Theft, Loss or Release of Select Agents and Toxins." More information about reporting a release of a select agent or toxin is available at: www.selectagents.gov/form3.html. The U.S. Department of Transportation also has reporting requirements for release of hazardous materials. Refer to the next section regarding Department of Transportation Hazardous Materials Regulations requirements.
   • Complete the information for Section 3 (on page 2) of the APHIS/CDC Form 2 and send one copy to the sender and one copy to AgSAS or DSAT within 2 business days of receipt.
   • If the package is not received within 48 hours of expected delivery time immediately contact AgSAS (phone: 301-851-3300 (option 3); fax: 301-734-3652) or DSAT (phone: 404-718-2000; fax: 404-471-8468) and submit APHIS/CDC Form 3 "Report of Theft, Loss or Release of Select Agents and Toxins." More information about reporting a theft or loss of a select agent or toxin is available at: www.selectagents.gov/form3.html.

   
   

General questions about transport of select agents and toxins

1. What are some of the specific measures required to ensure that infectious substances are shipped safely?

   Department of Transportation Hazardous Materials Regulations (49 CFR Parts 171-180)
   The Department of Transportation's (DOT) Pipeline and Hazardous Materials Safety Administration (PHMSA) has specific requirements for transporting infectious substances safely by motor vehicle, railcar, vessel, and aircraft. These requirements must be followed by domestic and international shippers and carriers. They also contain provisions on how to apply international regulations for hazardous materials. PHMSA's requirements for infectious substances are outlined below and explained in detail in the Department of Transportation (DOT) publication, "Transporting Infectious Substances Safely." This document is available at: phmsa.dot.gov/staticfiles/PHMSA/DownloadableFiles/Files/Transporting_Infectious_Substances_brochure.pdf

   Category A Infectious Substances
   Category A infectious substances are capable of causing permanent disability, life threatening or fatal disease to humans or animals when exposure to them occurs. Category A infectious substances have two shipping names: "Infectious substances, affecting humans (UN 2814)" or "Infectious substances, affecting animals (UN 2900)." Examples of Category A substances can be found in the DOT publication "Transporting Infectious Substances Safely." This document is available at: phmsa.dot.gov/staticfiles/PHMSA/DownloadableFiles/Files/Transporting_Infectious_Substances_brochure.pdf

   Packaging of Category A Infectious Substances
   See CFR 49, section 173.196. Category A infectious substances must be shipped in a triple package that consists of a watertight primary receptacle or receptacles; a watertight secondary packaging (for liquid materials, the secondary packaging must contain absorbent material in sufficient quantities to absorb the entire contents of the primary receptacles); and a rigid outer packaging which must be of adequate strength for its capacity, mass, and intended use. Page 29 of the DOT " Transporting Infectious Substances Safely " ( https://hazmatonline.phmsa.dot.gov/services/publication_documents/Transporting Infectious Substances Safely.pdf) document provides a diagram of how to properly package a Category A infectious substance. The maximum quantity of Category A infectious substance that can be shipped by air in one package is 4 L or 4 kg. The maximum quantity of Category A infectious substance that can be shipped by air in one package is 4 L or 4 kg. The maximum allowable quantity on passenger cargo aircraft is 50 ml or 50 g. The package must be a UN certified tested package marked : UN 4G/Class 6.2.

   Labeling of Category A Infectious Substances
   The outer container of all Category A infectious substance packages must display the following on one side of the package:

   • Sender's name and address
   • Recipient's name and address
   • Infectious substance label
   • Proper shipping name, UN number, and net quantity of infectious substance
   • Name and telephone number of person responsible for shipment
   • Cargo Aircraft Only label when shipping over 50 ml or 50 g
   • Class 9 label, including UN 1845, and net weight if packaged with dry ice and identified as Carbon Dioxide, solid

   
   

   Category B Infectious Substances
   See CFR 49, section 173.196. Category B infectious substances are infectious substances not in a form generally capable of causing permanent disability or life-threatening or fatal disease in otherwise healthy humans or animals when exposure to it occurs. This includes Category B infectious substances transported for diagnostic or investigational purposes. Category B infectious substances have the proper shipping name "Biological Substance, Category B" and the identification number UN 3373.

   Packaging of Category B Infectious Substances
   Category B infectious substances must be shipped in a triple package consisting of a leak proof primary receptacle or receptacles; leak proof secondary packaging (for liquid materials, the secondary packaging must contain absorbent material in sufficient quantities to absorb the entire contents of the primary receptacles); and rigid outer packaging. Page 31 of the DOT " Transporting Infectious Substances Safely " ( https://hazmatonline.phmsa.dot.gov/services/publication_documents/Transporting Infectious Substances Safely.pdf ) document provides a diagram of how to properly package a Category B infectious substance. The maximum quantity for a primary receptacle is 500 ml or 500g and outer packaging must not contain more than 4 L or 4 kg for transportation via cargo or passenger aircraft. Category B packages are not UN certified, but must be capable of passing prescribed test of a 4 foot drop test.

   Labeling of Category B Infectious Substances
   The outer container of all Category B infectious substance packages must display the following on one side of the package:

   • Sender’s name/telephone number and address
   • Recipient's name and address
   • The words "Biological Substance, Category B"
   • UN 3373 label (4” label unless label cannot fit on package, then 2” minimum is acceptable)
   • Class 9 label, including UN 1845, and net weight if packaged with dry ice and identified as Carbon Dioxide, solid

   
   

   Diagnostic/Clinical Specimens
   Any human or animal material including, but not limited to, excreta, secreta, blood and its components, tissue and tissue fluids, being transported for diagnostic or investigational purposes, but excluding live infected animals. Diagnostic specimens are usually assigned to UN3373, unless the source patient or animal has or may have a serious human or animal disease which can be readily transmitted form one individual to another, directly or indirectly and for which effective treatment and preventable measures are not usually available in which case they must be assigned to UN2814 or UN 2900 and shipped as a Category A infectious substance.

   Packaging of Diagnostic/Clinical Specimens
   See CFR 49, 173.199. Diagnostic and clinical specimens must be shipped in a triple package consisting of a leak proof primary receptacle or receptacles; leak proof secondary packaging (for liquid materials, the secondary packaging must contain absorbent material in sufficient quantities to absorb the entire contents of the primary receptacles); and rigid outer packaging. Page 31 of the DOT publication " Transporting Infectious Substances Safely " ( https://hazmatonline.phmsa.dot.gov/services/publication_documents/Transporting Infectious Substances Safely.pdf ) document provides a diagram of how to properly package a Diagnostic Specimen. The maximum quantity for a primary receptacle is 500 ml or 500g and outer packaging must not contain more than 4 L or 4 kg for transportation via cargo or passenger aircraft.

   Labeling of Diagnostic/Clinical Specimens
   The outer container of all diagnostic/clinical specimen packages must display the following on one side of the package:

   • Sender’s name/telephone number and address
   • Recipient's name and address
   • The words "Biological Substance, Category B"
   • UN 3373 label
   • Class 9 label, including UN 1845, and net weight if packaged with dry ice and identified as Carbon Dioxide, solid

   
   

   Biological Products The DOT regulations (49 CFR 173.134(a)(2), http://edocket.access.gpo.gov/cfr_2007/octqtr/pdf/49cfr173.134.pdf ) describe a biological product as a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent arsenic compound) applicable to the prevention, treatment, or cure of a disease or condition of human beings or animals. These are products derived from living organisms that are manufactured and distributed in accordance with special licensing requirements, and are used either for prevention, treatment or diagnosis of disease in human or animals, or for development, experimental or investigational purpose. They include, but are not limited to, finished or unfinished products such as vaccines and diagnostic products.

   Packaging, Labeling and Shipping of Biological Materials
   A biological product that is suspected to contain a pathogen that meets the definition of a Category A or B infectious substance must be assigned to UN 2814, UN 2900, or UN 3373 as appropriate and shipped and packaging in accordance with those criteria.

   Biological products transported for final packaging, distribution, or uses by medical professionals are not subject to shipping regulations.

   Genetically Modified Organisms and Micro-organisms
   These are microorganisms and organisms in which genetic material has been purposely altered through genetic engineering in a way that does not occur naturally. They are divided into the following categories:

   1. Genetically modified microorganisms, which meet the definition of an infectious agent, must be classified as Category A or Category B and assigned UN 2814 or UN 2900.
      
   2. Animals, which contain or are contaminated with genetically modified microorganisms or organisms that meet the definition of an infectious substance must not be transported by air unless exempted by the States concerned.
      
   3. Genetically modified organisms, which are known or suspected to be dangerous to humans, animals or the environment, must not be transported by air unless exempted by the States concerned.
      
   4. Except when authorized for unconditional use by the states of origin, transit, and destination, genetically modified microorganisms which do not meet the definition of infectious substances but which are capable of altering animals, plants or microbiological substances in a way which is not normally the result of natural reproduction must be classified as Class 9.
      

   
   

   Genetically modified organisms, which do not meet the definition of an infectious substance and which are not otherwise included under (a) to (d) above, are not subject to these regulations.

   Packaging of Genetically Modified Organisms and Micro-organisms
   These materials must be packaged in the same manner as Category B infectious substances except there are no testing requirements for the packaging. The maximum allowable quantity per primary receptacle is 100 ml or 100 g. There is no maximum net quantity per package.

   Labeling of Genetically Modified Organisms and Micro-organisms
   The outer container of genetically modified organisms and micro-organisms must have the following labels:

   • Sender's name and address
   • Recipient's name and address
   • Class 9 label

   
   

   Definitions of Watertight/Leakproof Although the PHMSA's Hazardous Materials Regulations (HMR; 49 CFR Parts 171-180), do not specifically define the terms "watertight" and "leakproof," these terms under the HMR essentially mean the receptacles and packaging are designed and constructed in a manner that does not permit a liquid material to enter or escape. These regulations are available electronically at the U.S. Government Printing Office's website at: http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?sid=585c275ee19254ba07625d8c92fe925f&c=ecfr&tpl=/ecfrbrowse/Title49/49cfrv2_02.tpl.

   
   
2. What happens if a package containing a select agent or toxin is lost or damaged during shipment?

   Requirements for All Infectious Substances

   The DOT regulations (49 CFR 171.15 and 171.16) require each person in physical possession of a hazardous material, including an infectious substance, to report specific types of transportation incidents that involve these materials. Immediate reporting (no later than 12 hours) by telephone to the National Response Center at 1-800-424-8802 is required for incidents where fire, breakage, spillage, or suspected contamination occurs that involves the shipment of infectious substances other than a patient specimen or regulated medical waste ( See 49 CFR 171.15(b)(3)). In addition, a written report to DOT is required within 30 days of the discovery of the incident for any unintentional release of hazardous material from a packaging during transportation, including those covered under 49 CFR 171.15 ( See 49 CFR 171.16(a)). DOT regulations also require packages that contain infectious substances to be accompanied by several forms of hazard communication, as applicable, as well as labeled to indicate the infectious hazard ( See 49 CFR 172.432 for a depiction of the required label). This label currently includes a statement for immediately reporting a leaking or damaged package to the Public Health Authority.

   The WHO "Guidance on Regulations for the Transport of Infectious Substances," January 2009, available at http://www.who.int/csr/resources/publications/biosafety/WHO_HSE_EPR_2008_10/en/, also provides specific recommended procedures for spill cleanup. This guidance is available to the agencies that govern land, vessel, and air shipments. The recommended procedures reflect those contained in the WHO Laboratory Biosafety Manual, Third Edition, 2004. The manual can be found at: http://www.who.int/csr/resources/publications/biosafety/WHO_CDS_CSR_LYO_2004_11/en/.

   Special Requirements for Select Agents

   If a package containing select agents has not been received within 48 hours after the expected delivery time or has been damaged to the extent that a release of a select agent may have occurred, the recipient must immediately report this incident to DSAT or AgSAS. In addition to the initial reporting, the entity must follow up with a written report (APHIS/CDC Form 3 - Report of Theft, Loss, or Release of Select Agents and Toxins) within 7 calendar days of the incident. Specific guidance on this form is available at: http://www.selectagents.gov/form3.html. Additional guidance on specific scenarios which would require an entity to report a theft, loss, or release of a select agent to DSAT or AgSAS is available at: http://www.selectagent.gov/resources/CompleteTHEFT%20LOSS%20%20RELEASE%20guidance%20document%20June82010_FINAL.pdf. Upon receipt of the report of the incident, AgSAS or DSAT will review the report to determine the appropriate action, which could include requesting additional information, administrative action, inspection, and/or referral to the Federal Bureau of Investigation for further investigation. If there is a threat to the public, AgSAS or DSAT will notify the appropriate local, state, and federal agencies.

3. What are the specific regulations that govern the shipment of infectious substances?

   There are several domestic and international regulations that govern the shipment of infectious substances. These include:

   Domestic Regulations

   • Department of Transportation. 49 CFR Part 171-180, Hazardous Materials Regulations . Applies to the shipment of infectious substances in commercial transportation to, from, or within the United States. These regulations also authorize, with certain conditions and limitations, the commercial transportation of hazardous materials in accordance with the International Civil Aviation Organization's Technical Instructions for the Safe Transport of Dangerous Goods by Air (ICAO Technical Instructions), the International Maritime Dangerous Goods Code (IMDG Code), Transport Canada's Transportation of Dangerous Goods Regulations (Transport Canada TDG Regulations), and the International Atomic Energy Agency Regulations for the Safe Transport of Radioactive Material (IAEA Regulations). See 49 CFR 171.12(a) and 49 CFR Part 171, Subpart C. Information on these regulations may be obtained by calling (800) 467-4922 (Toll free) or (202) 366-4488 from 9:00 AM to 5:00 PM Eastern time, or at: http://www.phmsa.dot.gov/hazmat.
   • United States Postal Service (USPS). 39 CFR Part 20, International Postal Service (International Mail Manual), and Part 111, General Information on Postal Service (Domestic Mail Manual). Regulations on transporting infectious substances through the USPS are codified in Section 601.10.17 of the Domestic Mail Manual and Section 135 of the International Mail Manual. A copy of the Domestic and International Mail Manuals may be obtained from the Government Printing Office by calling Monday through Friday, 7:30 a.m. - 9:00 p.m. EST: (202) 512-1800 or (866) 512-1800 (Toll free). The Domestic Mail Manual is available at : http://pe.usps.com/text/dmm300/dmm300_landing.htm. The International Mail Manual is available at: http://pe.usps.gov/text/imm/welcome.htm.
   • Occupational Health and Safety Administration (OSHA). 29 CFR Part 1910.1030, Occupational Exposure to Bloodborne Pathogens. These regulations provide minimal packaging and labeling requirements for blood and body fluids when transported within a laboratory or outside of it. Information may be obtained from your local OSHA office or at: http://www.osha.gov/.

   
   

   International Regulations

   • Technical Instructions for the Safe Transport of Dangerous Goods by Air (Technical Instructions). International Civil Aviation Organization (ICAO). Applies to the shipment of infectious substances by aircraft and is recognized in the United States and by most countries worldwide. The HMR recognize and authorize the Technical Instructions as an alternative to complying with the HMR for packaging, marking, labeling, classifying, and describing hazardous materials transported by aircraft and by motor vehicle either before or after being transported by aircraft. See 49 CFR Part 171, Subpart C. A copy of these regulations may be obtained from the ICAO Document Sales Unit at (514) 954-8022, Fax: (514) 954-6769, E-mail: sales_unit@icao.int, or at: http://www.icao.int.
   • Dangerous Goods Regulations. International Air Transport Association (IATA). These instructions are issued by an airline association, based on the ICAO Technical Instructions, and followed by most airline carriers. However they do not have official standing under the HMR. A copy of these regulations is available at: http://www.iata.org/index.htm or http://www.who.int/en/, or by contacting the IATA Customer Care office at: Tel: (514) 390-6726 or (800) 716-6326 (Toll free), Fax: (514) 874-9659, or E-mail: custserv@iata.org.
   • The International Maritime Dangerous Goods Code. International Maritime Organization (IMO). This code is of mandatory application for all 155 contracting parties to the International Convention for the Safety of Life at Sea (SOLAS). Information on this code is available at: http://www.imo.org/Pages/home.aspx.
   • The Letter Post Manual . Universal Postal Union (UPU). This manual reflects the United Nations Recommendations using the ICAO provisions as the basis for shipments. The manual can be found at http://www.upu.int/en/activities/letter-post/letter-post-manual.html.

   
   
4. Who can package select agents and toxins for shipment?

   The packaging of a select agent or toxin must be performed by an individual approved by the HHS Secretary or APHIS Administrator for access to select agents and toxins. The individual who packages the select agent or toxin must ensure compliance with all applicable laws concerning packaging and shipping.

   “Chain of Custody” paperwork
   
   If the package containing select agents and toxins is packaged by the laboratory and labeled generically as "Category A infectious substances" as required by the DOT regulations, the package can be placed with other packages in the area that the entity uses for shipment of materials and does not need to be accompanied by "chain of custody" paperwork.

   However, if the select agents and toxins are sent to another area for packaging and shipping, "chain of custody" paperwork is required to document transfer from the laboratory to the area where packaging occurs. The area where packaging occurs must be listed on the entity's certificate of registration and must meet all the requirements outlined in the select agent regulations as for other registered areas listed on the entity’s certificate of registration. If Tier 1 select agents and toxins will be packaged in the shipping and receiving area, it must meet all provisions associated with Tier 1 requirements. All individuals who will have access to Tier 1 select agents or toxins must also meet Tier 1 requirements and be enrolled in the entity’s suitability assessment program. The area will also be inspected to ensure the entity’s compliance with the select agent regulations.

   
   
5. How to package and ship select agents and toxins?
   
   

   Select agents and toxins should be classified as a Category A infectious substance with a proper shipping description of “UN2814, Infectious substances, affecting humans, 6.2” or “UN 2900, Infectious substances, affecting animals". Select agents and toxins for shipment should be packaged following the basic triple packaging system that consists of a primary receptacle (a sealable specimen bag) wrapped with absorbent material, a secondary receptacle (watertight, leak-proof), an itemized list of the packaging’s contents placed between the secondary and outer package, and an outer shipping package. Prior to being offered and transported, a Category A infectious substance must be packaged in accordance with § 173.196 of the U.S. Department of Transportation’s (DOT’s) Hazardous Materials Regulations (HMR; 49 CFR Parts 171-180), and be accompanied by shipping papers, marking, labeling, and emergency response information as prescribed in 49 CFR Part 172, Subparts C, D, E, and G, respectively. The HMR excepts infectious substances from DOT placarding under the HMR. Shippers and carriers of Category A infectious substances must also meet hazardous material training requirements prescribed in 49 CFR Part 172, Subpart H, which include the creation of and training on an in-depth security plan if the shipper and carrier are transporting select agents.

   Please refer to the following guidance for additional information:

   • Transporting Infectious Substances Website
   • Are You Preparing Suspected Ebola Contaminated Waste for Transportation?
   • Transporting Infectious Substances Safely
   • Federal Hazmat Law: An Overview
   • When You Transport Hazardous Materials Internationally
   • Does Your Hazmat Training Measure Up?
   • Hazardous Materials Transportation Security Requirements
   • Guide for Preparing Shipping Papers

   
   

   For international transportation the following standards must also be met, as applicable:

   For transportation by air, the International Civil Aviation Organization Technical Instructions for the Safe Transport of Dangerous Goods by Air (ICAO TI), including Packing Instruction 620; and for transportation by vessel, the International Maritime Organization (IMO) International Maritime Dangerous Goods (IMDG) Code, including Packing Instruction 620. See 49 CFR Part 171, Subpart C.

   For questions regarding the transportation of specimens, the DOT HazMat Info Center can be reached at 1-800-467-4922.

   Commercial carrier or courier
   
   Once the package is ready for shipment, the entity should use their established procedures for providing the package to the commercial carrier. If the package is not identified as containing select agents or toxins it can be placed with other packages for pick up by commercial carrier. The transfer must comply with Section 16 (Transfers) of the select agent regulations and must be pre-authorized by the Federal Select Agent Program.

   Hand-delivered package
   
   While an entity may choose to hand deliver a package containing a select agent or toxin to another registered entity, it must still comply with Section 16 (Transfers) of the select agent regulations and the transfer must be pre-authorized by the Federal Select Agent Program. The individual who is hand carrying the package must be an individual approved by the HHS Secretary or APHIS Administrator to have access to select agents and toxins. The entity remains responsible for ensuring that all local, state or federal requirements for the transportation of hazardous materials are followed. The entity must ensure that adequate precautions are taken to prevent a theft, loss or release of the select agents and toxins.

   Importation of Select Agents Toxins via Hand-Delivered Package
   
   In order to ensure the security and safety of select agents and toxins, the Federal Select Agent Program will not approve the importation of select agent material unless it is to be transported into the U.S. 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 U.S. resident, be SRA-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 Service will write 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 the Animal and Plant Health Inspection Service (APHIS), the date, time, flight number, 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.

   Security Plan
   
   Section 11(c)(10) requires that the entity's security plan contain procedures for shipping select agents and toxins. The procedures should contain documented processes to ensure select agents and toxins are safeguarded against theft, loss, intentional release or unauthorized access when a select agent or toxin is: (1) ready to be packaged for transportation, or (2) packaged for shipment:

   • How the transfer is coordinated between the sender and intended recipient;
   • How the package will be tracked in transit to ensure that the intended recipient is aware of the package's expected arrival;

   If the entity temporarily stores packages identified as containing select agent or toxin at the loading dock (instead of packaged for shipment labeled generically as "Category A infectious substances" (i.e., "lost in crowd" concept)), this location must be on the entity's registration, the security plan must include how the entity temporarily stores and secures the select agents or toxins in these locations, and individuals with access to these packages must have SRA approval.

   
   
6. How should packages containing select agents and toxins be received by entity?
   
   

   Receipt of Packages by Entity
   
   The entity should use their established procedures for receiving packages from the commercial carrier. It should be noted that the package containing select agents and toxins is not considered "received" by the entity until the intended recipient takes possession of the package. If the package is not identified as containing select agents or toxins it will be considered "lost in the crowd" until received by the intended recipient and does not need to be accompanied by a “chain of custody” document. However, the entity should ensure that packages containing hazardous materials, including packages containing select agents and toxins, are provided to the intended recipient without delay to avoid the hazardous materials from being compromised (e.g., thawing of dry ice). For example, the entity can have the shipping and receiving personnel take the package directly to the intended recipient upon package arrival; have a secured location in the shipping area for the intended recipient to retrieve the package; or have the commercial carrier deliver the package directly to the intended recipient.

   Receipt by Intended Recipient
   
   The intended recipient or his/her designee must be an individual who is approved by the HHS Secretary or APHIS Administrator for access to select agents and toxins. Upon receipt of the shipment, the intended recipient must verify the contents. If there is a discrepancy noted, the entity must immediately notify Federal Select Agent Program. The Responsible Official must complete Section 3 of the APHIS/CDC Form 2 "Request to Transfer Select Agents and Toxins" verifying receipt of the select agent or toxin and send one copy of page 2 to the sender and one copy to the Federal Select Agent Program within 2 business days of receipt. If the package has been damaged to the extent that a release of the select agent or toxin may have occurred or has not been received within 48 hours of the expected delivery time, the Responsible Official must immediately report to the Federal Select Agent Program and complete APHIS/CDC Form 3, Report of Theft, Loss, or Release of Select Agents and Toxins.

   Security Plan
   
   Section 11(c)(10) requires that the entity's security plan contain procedures for receiving select agents and toxins. The procedures should contain documented processes to ensure select agents and toxins are safeguarded against theft, loss, intentional release or unauthorized access when a select agent or toxin is received by a person with approval to access select agents and toxins. The procedures should include:

   • How the transfer is coordinated between the sender and intended recipient;
   • How the package will be tracked in transit to ensure that the intended recipient is aware of the package's expected arrival;
   • How the package arrives to the intended recipient including if the individual is not available; and
   • How the entity handles unexpected shipments (when an entity receives a select agent that it had neither requested nor coordinated for, and therefore was not expecting).

   If the entity temporarily stores packages identified as containing select agent or toxin at the loading dock (instead of packaged for shipment labeled generically as "Category A infectious substances" (i.e., "lost in crowd" concept)), this location must be on the entity's registration, the security plan must include how the entity temporarily stores and secures the select agents or toxins in these locations, and individuals with access to these packages must have SRA approval.