2011-26224. Office of Biotechnology Activities; Recombinant DNA Research: Action Under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines)

AGENCY:

National Institutes of Health (NIH), Public Health Services (PHS), Department of Health and Human Services, (DHHS).

ACTION:

Notice of Final Action under the NIH Guidelines.

SUMMARY:

The Office of Biotechnology Activities (OBA) is updating Appendix B of the NIH Guidelines to specify the risk group (RG) classification for several common attenuated strains of bacteria and viruses that are frequently used in recombinant DNA research. OBA is also specifying the risk group for several viruses not previously listed in Appendix B. In addition, a reference to Appendix B will be added to Section II-A of the NIH Guidelines, which addresses the risk assessment for research with recombinant DNA.

Background: The NIH Guidelines provide guidance to investigators and local Institutional Biosafety Committees (IBCs) for setting containment for recombinant DNA research. Section II-A, Risk Assessment, instructs investigators and IBCs to make an initial risk assessment based on the RG of the agent (see Appendix B, Classification of Human Etiologic Agents on the Basis of Hazard). The RG of the agent often correlates with the minimum containment level required for experiments subject to the NIH Guidelines.

The classification of agents into various RG categories is based largely on their ability to cause human disease and the availability of treatments for that disease. For the most part, the organisms listed in Appendix B are wild-type, non-attenuated strains and a distinction is not made between the RG classification for the wild-type organism and a corresponding attenuated strain. A few attenuated strains are classified in Appendix B at a lower RG than that of the wild-type organism. However, there are a number of well-established attenuated strains commonly employed in research that are not specifically listed and thus by default are included in the same RG as the wild-type organism. Therefore, the biosafety level (BL) specified for research subject to the NIH Guidelines may be identical for experimentation with either the attenuated or the wild-type strain.

OBA has conducted an evaluation of certain attenuated strains, focusing on those for which a risk assessment had been undertaken and containment recommendations determined in the Centers for Disease Control and Prevention (CDC)/NIH publication Biosafety in Microbiological and Biomedical Laboratories (BMBL) (5th edition). In addition, the NIH Recombinant DNA Advisory Committee (RAC) discussed the appropriate containment for two attenuated strains of Yersinia pestis (lcr^(-) and pgm^(-) mutants) at its meeting on June 16, 2010. (A webcast of that discussion is available at http://oba.od.nih.gov/​rdna_​rac/​rac_​past_​meetings_​2010.html.)

Specifying the risk groups for attenuated strains in Appendix B of the NIH Guidelines will lead to more uniform containment recommendations that are commensurate with the biosafety risk. In addition, OBA has identified several RG3 viruses that are not currently specified in Appendix B or are a member of a family of viruses otherwise classified as RG2. Therefore, Appendix B is being updated to address these viruses as well.

OBA consulted the NIH RAC as well as other subject matter experts from NIH, CDC, and academia. These proposed changes were published in the Federal Register (76 FR 44339) on July 25, 2011, and one comment was received. This comment, from the American Biological Safety Association (ABSA), suggested that “OBA should consider adding additional information to Section II-A-3 covering the assignment of Risk Group to commonly used attenuated strains.” Section II-A of the NIH Guidelines provides a framework for conducting a comprehensive risk assessment. These proposed changes to Appendix B and ABSA's comment were discussed at the September 13, 2011, meeting of the RAC. OBA and the RAC appreciated ABSA's comments and will add a reference to Appendix B to the last sentence of the first paragraph of Section II-A-3. The last sentence of the first paragraph of Section II-A-3 currently reads: “Certain attenuated strains or strains that have been demonstrated to have irreversibly lost known virulence factors may qualify for a reduction of the containment level compared to the Risk Group assigned to the parent strain (see Section V-B, Footnotes and References of Sections I-IV).” It will be amended to read:

Certain attenuated strains or strains that have been demonstrated to have irreversibly lost known virulence factors may qualify for a reduction of the containment level compared to the Risk Group assigned to the parent strain (see Appendix B, Classification of Human Etiologic Agents on the Basis of Hazard and Section V-B, Footnotes and References of Sections I-IV).

In addition to the change to the first paragraph of Section II-A-3, the following additions will be made to Appendix B-II-A. Risk Group 2 (RG2)—Bacterial Agents Including Chlamydia:

Coxiella burnetii, Nine Mile strain, plaque purified, clone 4.

*Francisella tularensis subspecies novicida (also referred to as Francisella novicida) strain, Utah 112.

*Francisella tularensis subspecies holartica LVS.

*Francisella tularensis biovar tularensis strain ATCC 6223 (also known as strain B38).

Yersinia pestis pgm^(-) (lacking the 102 kb pigmentation locus).

Yersinia pestis lcr^(-) (lacking the LCR plasmid).

The following footnote will be added regarding research with attenuated strains of Francisella:

*For research involving high concentrations, BL3 practices should be considered (See Appendix G-II-C-2).

The following changes/additions will be made to Appendix B-II-D Risk Group 2 (RG2)—Viruses:

Alphaviruses (Togaviruses)—Group A Arboviruses:

“Venezuelan equine encephalomyelitis vaccine strain TC-83” will be changed to:

Venezuelan equine encephalomyelitis vaccine strains TC-83 and V3526.

Alphaviruses (Togaviruses)—Group A Arboviruses:

Add: Chikungunya vaccine strain 181/25.

Arenaviruses:

Add: Junin virus candid #1 vaccine strain.

Flaviviruses (Togaviruses)—Group B Arboviruses:

Add: Japanese encephalitis virus strain SA 14-14-2.

Rhabdoviruses:

“Vesicular stomatitis virus—laboratory adapted strains including VSV—Indiana, San Juan, and Glasgow” will be changed to:

Vesicular stomatitis virus non-exotic strains: VSV—Indiana 1 serotype strains (e.g. Glasgow, Mudd-Summers, Orsay, San Juan) and VSV—New Jersey serotype strains (e.g. Ogden, Hazelhurst).

The following additions will be made to Appendix B-III-D Risk Group 3 (RG3)—Viruses and Prions:

Add: Coronaviruses:

Add: SARS-associated coronavirus (SARS—CoV).

Alphaviruses (Togaviruses)—Group A Arboviruses:

Add: Chikungunya.

Flaviviruses (Togaviruses)—Group B Arboviruses:

Add: West Nile virus (WNV).

Dated: October 3, 2011.

Jacqueline Corrigan-Curay,

Acting Director, Office of Biotechnology Activities, National Institutes of Health.