Policy Statement: Laboratory Work with Regulated Genomes

Date: February 14, 2020

Subject: Revised FSAP Policy Statement: FSAP Policy Statement: Laboratory work with the full-length genomes capable of producing infectious virus of regulated Risk Group 3 and 4 (RG3 and RG4) select agents and Veterinary Services (VS) select agents at one containment level lower than the infectious virus without RNA inactivation

This policy statement replaces the FSAP Policy Statement: “Laboratory work with the regulated full-length genomes of regulated Risk Group 3 and 4 (RG3 and RG4) agents at one containment level lower than the infectious virus without RNA inactivation” dated August 13, 2014.

Policy Statement:

The FSAP received recommendations from a group of Federal subject matter experts (SME) regarding working safely with regulated genomes at lower containment if certain conditions are met. Based upon the SME recommendations, it is the policy of the FSAP that a registered entity can perform laboratory work with the full-length genomes of regulated Risk Group 3 and 4 [1] (RG3 [2] and RG4 [3]) agents and VS select agents at one containment level lower than the infectious virus without RNA inactivation.

Note: Regardless of the biosafety level used, the full-length genomes of any of the select agent viruses capable of producing infectious virus are regulated and must be handled in registered space.

If working with genomic material from a Tier 1 positive strand RNA virus (currently only Foot-and-mouth disease virus (FMDv)), lower containment laboratories would still have to maintain the Tier 1 requirements. To work with RG3, RG4 and VS (+) ssRNA genomic material in laboratories one containment level lower than the level required for the infectious virus, the following additional safety practices must be in place:

• The genomic material must be free of infectious virus, as required in 42 C.F.R. 73.3(d)(4) and 73.4(d)(4), and 9 C.F.R. 121.3(d)(4) and 121.4(d)(4), before removing the genomic material from the laboratory  designated to work with the live virus.
• For RG4 and FMDv genomic work in BSL-3 laboratories, work must be performed inside a biosafety cabinet (BSC).
• For RG3 and VS agents (other than FMDv) genomic work in BSL-2 laboratories, work should be based on a risk assessment by the entity, although work in the BSC is preferred.
• No concurrent work with mammalian cell culture or in vitro translation experiments are conducted in the same laboratory.
• No concurrent transfection work or in vitro translation reagents are used or stored in the same laboratory.
• Personal protective equipment (PPE) must afford adequate mucosal membrane protection to avoid the risk of auto-inoculation and include the following:
  • Disposable or suite-dedicated lab coats.
  • Protective eyewear or face shield.
  • Gloves (latex, vinyl, nitrile, etc.) are chosen to resist those chemicals and or solvents used in cloning procedures.
• Avoid glassware – plastic ware is recommended.
• Avoid sharps, including needles and syringes.

Authority:

For biological agents and toxins determined by HHS to have the potential to pose a severe threat to public health and safety (select agents and toxins), the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (42 U.S.C. 262a) directs the promulgation of regulations to establish and enforce safety procedures for the possession, use and transfer of select agents and toxins, including measures to ensure proper training and appropriate skills to handle such agents and toxins.  42 U.S.C. § 262a(c).

For biological agents and toxins determined by USDA to have the potential to pose a severe threat to animal health or animal products (select agents and toxins), the Agricultural Bioterrorism Act of 2002 (7 U.S.C. 8401) directs the promulgation of regulations to establish and enforce safety procedures for the possession and use of such select agents and toxins, including measures to ensure proper training and appropriate skills to handle such select agents and toxins. 7 U.S.C. 8401(c).

Federal regulations require that for entities that possess select agents and toxins their “biosafety and containment procedures must be sufficient to contain the select agent or toxin (e.g., physical structure and features of the entity, and operational and procedural safeguards).”  See 42 CFR 73.12(b), 9 CFR 121.12(b).  Zoonotic select agents and toxins are regulated by both HHS and USDA.  See 42 CFR 73.4 and 9 CFR 121.4.

[1] NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules, Appendix B.
[2] Agents that are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available (high individual risk but low community risk)
[3] Agents that are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available (high individual risk and high community risk)