[Federal Register Volume 76, Number 142 (Monday, July 25, 2011)]
[Notices]
[Pages 44339-44340]
From the Federal Register Online via the Government Printing 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 oba@od.nih.gov, 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]
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