[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]
BILLING CODE 4140-01-P