[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]
[[Page 3150]]
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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]
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