[Federal Register Volume 75, Number 138 (Tuesday, July 20, 2010)]
[Notices]
[Pages 42114-42115]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-17668]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Office of Biotechnology Activities; Recombinant DNA Research:
Proposed Action Under the NIH Guidelines for Research Involving
Recombinant DNA Molecules (NIH Guidelines)
AGENCY: National Institutes of Health (NIH), PHS, DHHS.
ACTION: Notice of proposed action under the NIH Guidelines.
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SUMMARY: Under the NIH Guidelines, experiments involving the generation
of transgenic rodents by recombinant DNA technology must 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).
The NIH Office of Biotechnology Activities (OBA) received a request
that the breeding of well-characterized transgenic rodents that can be
maintained under BL1 conditions be exempt from the NIH Guidelines. The
rationale is that these experiments pose little if any biosafety risk
and therefore the requirement for registration with the IBC may impose
an administrative burden without enhancing the safe conduct of this
research. In response to this request, OBA brought a proposal to amend
the NIH Guidelines to the Recombinant DNA Advisory Committee (RAC) for
consideration. The initial proposal was discussed at the March 11, 2010
RAC meeting and a revised proposal was discussed at the June 16, 2010
RAC meeting (Webcasts of these discussions are available at http://oba.od.nih.gov/rdna_rac/rac_meetings.html). The RAC endorsed a
proposal that would exempt from the NIH Guidelines the breeding of
almost all transgenic rodents that can be housed at BL1, with the
exception of rodents that contain a gene 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.
This notice seeks public comment on this proposal.
DATES: The public is encouraged to submit written comments on these
proposed changes. 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. All comments
received by September 1, 2010 will be considered. All written comments
received in response to this notice will be available for public
inspection in the NIH OBA office, 6705 Rockledge Drive, Suite 750, MSC
7985, Bethesda, MD 20892-7985, (Phone: 301-496-9838) 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 proposed changes, please contact OBA
by e-mail at [email protected], or telephone at 301-496-9838. Comments can
be submitted to the same email address or by fax to 301-496-9839 or
mail to the Office of Biotechnology Activities, National Institutes of
Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, Maryland
20892-7985.
Background: Section III-E of the NIH Guidelines addresses
experiments for which IBC notification 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 therefore
although IBC review and approval is still required, such approval need
not be obtained prior to initiating research. This is in contrast to
all other covered experiments described in the NIH Guidelines for which
IBC review and approval is required prior to initiation of the
experiment.
Under the NIH Guidelines, certain experiments can be exempted from
the NIH Guidelines if they do not present a significant risk to public
health or the environment (Section III-F-6). These exemptions are
delineated in Appendix C of the NIH Guidelines. OBA was recently
approached regarding the Section III-E-3 requirement to register the
breeding of transgenic rodents and whether such experiments met the
criteria for exemption under Section III-F-6. OBA sought the advice of
the RAC on this issue.
Currently, the purchase or transfer of transgenic rodents that
require BL1 containment are exempt from the NIH Guidelines. This
proposal would extend that exemption to almost all experiments that
involve the generation of transgenic rodents by breeding, as long as
the transgenic rodents are appropriate to be maintained under BL1
conditions. The rationale is that three decades of experience working
with and breeding transgenic rodents has demonstrated that the
overwhelming majority of experiments involving breeding of transgenic
rodents that can be housed under BL1 conditions result in a rodent that
can be appropriately housed under BL1 conditions. These breeding
experiments do not pose an appreciable risk to human health or to the
environment. In addition, while the registration with the IBC is not a
significant burden, the total number of registrations required
constitutes 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 some breeding experiments for which IBC
registration would be required in order to ensure that a risk
assessment is conducted and that the resulting rodent is disposed of
appropriately. The proposed exemption would retain the requirement to
register with the IBC when the genome of one of the parental transgenic
rodents contains more than 50 percent of the genome of an exogenous,
eukaryotic virus from a single family or if the transgenic rodent's
transgene is under the control of a gammaretroviral long terminal
repeat (LTR). The restriction regarding exogenous eukaryotic viruses is
designed to prevent inadvertent reconstitution of an exogenous virus in
the resultant transgenic mouse. The restriction regarding transgenes
under control of a gammaretroviral long terminal repeat addresses 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.,
MLV, XMRV, FeLV), the requirement for registration is limited to
rodents containing a transgene under control of these LTRs.
Specifically, the following changes are proposed 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 with 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:
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Both parental rodents can be housed under BL1 containment, and
neither parental transgenic rodent contains the following genetic
modifications:
(a) More than one-half of the genome of an exogenous virus from a
single Family of viruses; or
(b) A transgene that is under the control of a gammaretroviral long
terminal repeat (LTR); and
It is anticipated that the transgenic rodent that results from this
breeding:
(a) Will contain no 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
would be renumbered to Appendix C-VIII and Appendices C-VIII-A though
C-VIII-E, respectively.
For clarity the following will be added to Section III-E-3.
Section III-E-3-a. Experiments involving the breeding of certain
BL1 transgenic rodents are exempt under Section III-F, Exempt
Experiments (See Appendix C-VII, Generation of BL1 Transgenic Rodents
via Breeding).
Dated: July 9, 2010.
Jacqueline Corrigan-Curay,
Acting Director, Office of Biotechnology Activities, National
Institutes of Health.
[FR Doc. 2010-17668 Filed 7-19-10; 8:45 am]
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