Guidance on the Regulation of Select Agent and Toxin Nucleic Acids: FSAP Regulated Genomes

Working with FSAP Regulated Genomes at Lower Containment Policy

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), 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 this laboratory
  • No concurrent transfection work or in vitro translation reagents are used or stored in this 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 as required by procedure
    • 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

[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)

Page last reviewed: August 27, 2020, 04:05 PM