[Federal Register Volume 76, Number 12 (Wednesday, January 19, 2011)]
[Notices]
[Pages 3150-3151]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-1037]



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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), PHS, DHHS.

ACTION: Action under the NIH Guidelines.

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SUMMARY: The NIH Guidelines currently require that recombinant DNA 
experiments designed to create new transgenic rodents be registered 
with the Institutional Biosafety Committee (IBC). Specifically, Section 
III-E-3 of the NIH Guidelines addresses the generation of transgenic 
rodents that may be housed under biosafety level (BL) 1 conditions and 
allows the work to proceed simultaneously with registration of the 
experiment with the IBC. The IBC must then review and approve the 
experiment. The NIH Guidelines address two pathways for generation of a 
transgenic rodent: altering the animal's genome using recombinant DNA 
technology, or breeding one or more transgenic rodents to create a new 
transgenic rodent (i.e., breeding of two different transgenic rodents 
or the breeding of a transgenic rodent and a non-transgenic rodent).
    On July 20, 2010 the NIH Office of Biotechnology Activities (OBA) 
published a proposed action (75 FR 42114) to amend Section III-E-3 and 
to add a new Section to Appendix C (Appendix C-VII) of the NIH 
Guidelines so as to exempt breeding of almost all transgenic rodents 
that can be housed at BL1, with the exception of rodents that contain a 
transgene encoding more than fifty percent of an exogenous eukaryotic 
virus and transgenic rodents in which the transgene is under the 
control of a gammaretroviral promoter. After receiving public comment 
on the proposed changes, OBA is implementing these changes.

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, MSC 7985, Bethesda, Maryland 20892.
    Background: Section III-E of the NIH Guidelines addresses 
experiments for which IBC registration is required at the time the 
research is initiated. Experiments covered in this section of the NIH 
Guidelines are considered to be of low biosafety risk and although IBC 
review and approval is still required, such approval need not be 
obtained prior to initiating the research. This is in contrast to all 
other experiments described in the NIH Guidelines for which IBC review 
and approval is required prior to initiation of the experiment.
    Under the NIH Guidelines (Section III-F-6), certain experiments can 
be exempted from the NIH Guidelines if they do not present a 
significant risk to public health or the environment and the NIH 
Director approves this action. These exemptions are delineated in 
Appendix C of the NIH Guidelines.
    Currently, the purchase or transfer of transgenic rodents that 
require BL1 containment are exempt from the NIH Guidelines under 
Appendix C. This action would extend that exemption to most experiments 
that involve the generation of transgenic rodents by breeding, as long 
as the transgenic rodents can be appropriately maintained under BL1 
conditions. The rationale for this change is that three decades of 
working with and breeding transgenic rodents have demonstrated that the 
overwhelming majority of experiments involving breeding of transgenic 
rodents that can be housed under BL1 conditions results in progeny that 
can also be housed under BL1 conditions. Thus these breeding 
experiments do not pose an appreciable risk to human health or to the 
environment. In addition, while registration with the IBC is not a 
significant burden, the total number of registrations required can 
constitute a significant collective administrative burden on the IBC 
and researchers that does not appear to be commensurate with the very 
low biosafety risk.
    There are still two categories of breeding experiments for which 
IBC registration will be required in order to ensure that a risk 
assessment is conducted and that the resulting rodent is disposed of 
appropriately:
    (a) Breeding experiments involving transgenic rodents that contain 
more than 50 percent of the genome of an exogenous eukaryotic virus 
from a single family, in order to prevent inadvertent reconstitution of 
an exogenous virus in the resultant transgenic rodent; and
    (b) breeding experiments in which the transgenic rodent's transgene 
is under the control of a gammaretroviral long terminal repeat (LTR), 
in order to address the small risk of recombination with endogenous 
retroviruses which could potentially result in mobilization of the 
transgene via a replication-competent mouse retrovirus.
    As the risk of recombination and possible transmission to humans is 
more likely with gammaretroviral LTRs (e.g., murine leukemia virus, 
feline leukemia virus, xenotropic murine leukemia-related virus), the 
requirement for registration is limited to rodents containing a 
transgene under control of these LTRs.
    OBA received nine comments in response to the July 20, 2010 Federal 
Register notice of proposed changes. All were supportive of the change 
and emphasized that the current registration requirements impose a 
significant administrative burden on IBCs that is not necessary to 
protect public health, laboratory workers or the environment. One 
comment noted that making these experiments exempt would free up 
valuable resources (time and money) for their IBC, Institutional Animal 
Care and Use Committee, and researchers. One comment asked for 
clarification regarding how to assess whether breeding a transgenic 
rodent containing a partial gammaretroviral LTR sequence must be 
registered with the IBC. The key issue is not the percentage of the LTR 
sequence, but rather whether it is functional or not, i.e. whether 
there is sufficient LTR sequence to direct the expression of a 
transgene.
    The following changes will be made to Appendix C of the NIH 
Guidelines:

Appendix C-VII. Generation of BL1 Transgenic Rodents via Breeding

    The breeding of two different transgenic rodents or the breeding 
of a transgenic rodent and a non-transgenic rodent with the intent 
of creating a new strain of transgenic rodent that can be housed at 
BL1 containment will be exempt from the NIH Guidelines if:
    (1) Both parental rodents can be housed under BL1 containment; 
and
    (2) Neither parental transgenic rodent contains the following 
genetic modifications:
    (a) Incorporation of more than one-half of the genome of an 
exogenous eukaryotic virus from a single family of viruses; or
    (b) Incorporation of a transgene that is under the control of a 
gammaretroviral long terminal repeat (LTR); and
    (3) The transgenic rodent that results from this breeding is not 
expected to contain more than one-half of an exogenous viral genome 
from a single family of viruses.

    The current Appendix C-VII and Appendices C-VII-A through C-VII-E 
will be renumbered to Appendix C-VIII and Appendices C-VIII-A though C-
VIII-E, respectively.
    For clarity the following is added to Section III-E-3.
    Section III-E-3-a. Experiments involving the breeding of certain 
BL1

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transgenic rodents are exempt under Section III-F, Exempt Experiments 
(See Appendix C-VII, Generation of BL1 Transgenic Rodents via 
Breeding).

    Dated: January 10, 2011.
Jacqueline Corrigan-Curay,
Acting Director, Office of Biotechnology Activities, National 
Institutes of Health.
[FR Doc. 2011-1037 Filed 1-18-11; 8:45 am]
BILLING CODE 4140-01-P