Example Scenarios Involving Synthetic Genomic Select Agent Materials

1. An individual submits to a producer (facility that manufactures the material) a full genome sequence of Foot-and-Mouth Disease Virus (FMDV) and requests that it be synthesized and shipped to the submitter (individual that requests the material).

   • Does the processing of this order fall under the current select agent regulations?

     Yes. An individual or entity in possession of the full FMDV genome, regardless of how the individual or entity came into possession of it, or for however brief a time period, would be required to be pre-registered under provisions of the select agent regulations, meeting all of the safety, security and personnel reliability requirements therein. Transfer of the full FMDV genome would require prior approval from the select agent program.

   • Does the sequence information that this individual submitted fall under the current select agent regulations?

     No. The current regulations do not cover sequence information.

   • The producer is registered with the Select Agent Program for possession of infectious FMDV genomic material. Once this material is produced, can the producer send it to the submitter?

     Yes, with stipulations. First, the submitter must also be registered with the Select Agent Program to possess select agents. Second, all domestic transfers of select agents must be preauthorized by either the CDC or APHIS Select Agent Program. All international exports must be preauthorized by the Department of Commerce. Since the producer is registered with the Select Agent Program, the Program must first authorize the domestic transfer. Instructions and forms for use in obtaining this authorization are available on the National Select Agent Registry website (www.selectagents.gov).

2. An individual submits an unidentified sequence to a producer and asks for its synthesis. Screening of this sequence by the producer shows a high degree of homology with the pXO2 virulence-associated plasmid of Bacillus anthracis.

   • Does the processing of this order fall under the current select agent regulations?

     No. Although B. anthracis organisms are regulated, the current regulations do not cover individual B. anthracis genetic elements. Unless the functional form of a select agent toxin is included in the product, select agent bacterial genomic material is not covered by the current regulations. However, all international exports of B. anthracis genetic elements associated with pathogenicity must be preauthorized by the Department of Commerce. Instructions for obtaining an export license are available on the Bureau of Industry and Security website, www.bis.doc.gov.

3. An individual submits a genomic sequence for Yersinia pestis and asks for its synthesis.

   • Does the processing of this order fall under the current select agent regulations?

     It depends. If the functional form of a select agent is included in the product, then it would fall under the select agent regulations. Otherwise, select agent bacterial and fungal genomes are not covered under the regulations. However, all international exports of Y. pestis genetic elements associated with pathogenicity must be preauthorized by the Department of Commerce. Instructions for obtaining an export license are available on the Bureau of Industry and Security website, www.bis.doc.gov.

4. An investigator in Canada submits an order for the synthesis and delivery to Canada of the genome of the Omsk Hemorrhagic Fever virus from a producer located in the United States.

   • Does the processing of this order fall under the current select agent regulations?

     Yes. The possession of this material is regulated by the select agent regulations and the entity performing the synthesis would have to be registered with the Select Agent Program. However, because the material is to be exported, it will require an export license from the U.S. Department of Commerce, Bureau of Industry and Security instead of a Select Agent Program authorization. Instructions for obtaining this license are available on the Bureau of Industry and Security website, www.bis.doc.gov.

5. A foreign national works at a laboratory and is trained to grow Eastern Equine Encephalitis virus (EEE) in order to produce a vaccine.

   • Does this activity fall under the current select agent regulations?

     Yes. The facility housing this work would have to be registered with the Select Agent Program and the foreign national involved in this work would have to have a clear Select Agent Security Risk Assessment in order to access the virus. In addition, there are “deemed export” licensing requirements from the Department of Commerce for the transfer of production technology to the foreign national working in the United States. An export license is required to transfer the technology to produce the EEE (1E001). Even though the final end use is a vaccine which is controlled under 1C991, the technology involves the virus strain and thus controlled. Instructions for obtaining an export license are available on the Bureau of Industry and Security website, www.bis.doc.gov.

6. A synthetic genomics producer located outside the U.S. receives an order from a laboratory within the U.S. for the genome of the Russian Spring and Summer encephalitis virus.

   • Does this activity fall under the current select agent regulations?

     Yes, in part. Although the producer is not required to follow the select agent regulations, the receiving laboratory must be registered with the Select Agent Program. In addition, the receiving laboratory must obtain an import permit from the CDC's Etiologic Agent Import Permit Program prior to importing this material. Information on obtaining import permits can be obtained from the National Select Agent Registry website (www.selectagents.gov).