[Federal Register Volume 76, Number 142 (Monday, July 25, 2011)]
[Notices]
[Pages 44339-44340]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-18726]



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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, PHS, Department of Health and 

Human Services.



ACTION: Proposed Minor Action under the NIH Guidelines.



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SUMMARY: The Office of Biotechnology Activities (OBA) is updating 

Appendix B of the NIH Guidelines by specifying 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 adding the risk group for several viruses not previously listed in 

Appendix B. 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 establishes 

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 of organisms 

are classified in Appendix B at a lower RG than that of the parental 

organism. However, there are a number of additional, well-established 

attenuated strains employed in research subject to the NIH Guidelines 

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 therefore 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). Specifying the risk groups for these 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 currently specified as a member of a 

family of viruses otherwise classified as RG2. Therefore, Appendix B is 

being updated to address these viruses as well.

    In addition to considering the risk assessment articulated in the 

BMBL, OBA also consulted with members of the NIH Recombinant DNA 

Advisory Committee (RAC) as well as other subject matter experts from 

NIH, CDC, and academia. Of note, the RAC discussed the appropriate 

containment for two attenuated strains of Yersinia pestis 

(lcr(-) and pgm(-) mutants) at its June 16, 2010, 

meeting when the committee considered which antibiotic markers could be 

used in these strains without requiring RAC review under Section III-A-

1-a. (A webcast of that discussion is available at http://oba.od.nih.gov/rdna_rac/rac_past_meetings_2010.html.) The RAC 

recommendations regarding containment for work with these attenuated 

strains of Yersinia pestis are being implemented by amending Appendix B 

to indicate that these specific strains are RG2 organisms rather than 

RG3 organisms.

    This update does not include all attenuated strains identified in 

the BMBL. OBA has tried to select attenuated strains commonly used in 

recombinant DNA research. OBA has also not modified the RG for viruses 

for which the NIH Guidelines already provides specific containment 

recommendations. For example, human immunodeficiency virus (HIV) is 

currently classified as a RG3 virus in Appendix B of the NIH 

Guidelines. However, Section II-A-3 makes specific recommendations 

regarding when BL2 is acceptable for research with HIV and OBA's 

guidance titled Biosafety Considerations for Research with Lentiviral 

Vectors (see http://oba.od.nih.gov/rdna_rac/rac_guidance_lentivirus.html) provides additional containment recommendations for 

lentiviral vectors derived from HIV.

    Revision of Appendix B is considered a Minor Action under Section 

IV-C-3 of the NIH Guidelines and therefore can be implemented by OBA 

after consultation



[[Page 44340]]



with the RAC Chair and one or more RAC members as needed. This 

consultation is complete. However, in the interest of soliciting broad 

public input, OBA is submitting this action for public comment and will 

finalize the changes after reviewing any comments.



DATES: The public is encouraged to submit written comments on this 

minor action. Comments may be submitted to the OBA in paper or 

electronic form at the OBA mailing, fax, and e-mail addresses shown 

below under the heading FOR FURTHER INFORMATION CONTACT. The NIH will 

consider all comments submitted by September 9, 2011. All written 

comments received in response to this notice will be available for 

public inspection at the NIH OBA office, 6705 Rockledge Drive, Suite 

750, Bethesda, MD 20817-7985, weekdays between the hours of 8:30 a.m. 

and 5 p.m.



FOR FURTHER INFORMATION CONTACT: If you have questions, or require 

additional information about these changes, please contact OBA by e-

mail at [email protected], telephone (301-496-9838), or mail to the Office 

of Biotechnology Activities, National Institutes of Health, 6705 

Rockledge Drive, Suite 750, Bethesda, Maryland 20892-7985.

    Background: Appendix B of the NIH Guidelines is a list of 

biological agents that are classified into risk groups on the basis of 

their ability to cause disease in healthy adults and the availability 

of preventive or therapeutic interventions. Agents listed in Appendix B 

have been classified into one of four risk groups:

     RG1 agents are those that are not associated with disease 

in healthy adult humans;

     RG2 agents are those that are associated with human 

disease which is rarely serious and for which preventive or therapeutic 

interventions are often available;

     RG3 agents are associated with serious or lethal human 

disease for which preventive or therapeutic interventions may be 

available; and

     RG4 agents are those that are likely to cause serious or 

lethal human disease for which preventive or therapeutic interventions 

are not usually available.

    For the most part, the agents listed in Appendix B are wild-type, 

fully pathogenic strains. However, laboratory research that is subject 

to the NIH Guidelines frequently employs strains that are attenuated. 

An attenuated strain is not necessarily avirulent but generally is less 

pathogenic than the wild-type strain, and therefore the biosafety risk 

posed by research with an attenuated strain is not necessarily 

equivalent to that posed by the wild-type strain. As the RG of an agent 

is the starting point for the risk assessment to determine containment 

for research with that agent, OBA is amending Appendix B to provide 

more specific guidance for these attenuated strains.

    In addition to designating RGs for several attenuated strains, four 

additional changes will be made to Appendix B. The classification of 

attenuated strains of Vesicular stomatitis virus will be clarified. 

West Nile Virus (WNV) and Chikungunya virus are currently not 

specifically listed in the RG classification. WNV will now be listed as 

a RG3 Flavivirus and Chikungunya virus will be listed as a RG3 

Togavirus. In addition, the coronavirus that is the causative agent of 

severe acute respiratory syndrome (SARS) will be listed as a RG3 

coronavirus. All coronaviruses are currently RG2 viruses. The BMBL 

currently recommends BL3 containment for research with these three 

viruses.

    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, Utah112

    *Francisella tularensis subspeciesholartica 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 

(RG2 Viruses) of the NIH Guidelines:



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.





    The following will be added to Appendix B-II-D:



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 (RG3 

Viruses and Prions) of the NIH Guidelines:



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: July 18, 2011.

Jacqueline Corrigan-Curay,

Acting Director, Office of Biotechnology Activities, National 

Institutes of Health.

[FR Doc. 2011-18726 Filed 7-22-11; 8:45 am]

BILLING CODE 4140-01-P