[Federal Register Volume 76, Number 196 (Tuesday, October 11, 2011)]
[Notices]
[Pages 62816-62817]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-26224]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


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.

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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

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(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.
[FR Doc. 2011-26224 Filed 10-7-11; 8:45 am]
BILLING CODE 4140-01-P