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Federal Register / Vol. 59, No. 127 / Tuesday, July 5, T994 / Notices 
the ability of a specific microbiological 
agent or eukaryotic cell to self-replicate. 
Appendix K-VII-I. Incidental Release. 
An incidental release is the discharge of 
a microbiological agent or eukaryotic 
cell from a containment system that is 
expected when the system is 
appropriately designed and properly 
operated and maintained. 
Appendix K-VII-J. Minimization. 
Minimization is the design and 
operation of containment systems in 
order that any incidental release is a de 
minimis release. 
Appendix K-VII-K. Pathogen. A 
pathogen is any microbiological agent or 
eukaryotic cell containing'sufficient 
genetic information, which upon 
expression of such information, is 
capable of producing disease in healthy 
people, plants, or animals. 
Appendix K-VII-L. Physical Barrier. 
A physical barrier is considered any 
equipment, facilities, or devices (e.g., 
fermenters, factories, filters, thermal 
oxidizers) which are designed to 
achieve containment. 
Appendix K-VII-M. Release. Release 
is the discharge of a microbiological 
agent or eukaryotic cell from a 
containment system. Discharges can be 
Incidental or accidental. Incidental 
releases are de minimis in nature; 
accidental releases may be de minimis 
in nature. 
Appendix L. Release into the 
Environment of Certain Plants 
Appendix L-I. General Information 
Appendix L specifies conditions 
under which certain plants as specified 
below, may be approved for release into 
the environment Experiments in this 
categoiy cannot be initiated without 
submission of relevant information on 
the proposed experiment to NIH, review 
by the RAC Plant Subcommittee, and 
specific approval by the NIH Director. 
Such experiments iso require the 
approval of the Institutional Biosafety 
Committee before initiation. 
Appendix L-II. Criteria Allowing Review 
by the RAC Plant Subcommittee 
Without the Requirement for Full RAC 
Review 
In consultation with the RAC Plant 
Subcommittee and without the 
requirement for full RAC review 
(Institutional Biosafety Committee 
review and approval is necessary), NIH/ 
ORDA may approve the growing of 
plants containing recombinant DNA in 
the field under the following conditions: 
(i) The plant species is a cultivated crop 
of a genus that has no species known to 
be a noxious weed; (ii) the introduced 
DNA consists of well-characterized 
genes containing no sequences harmful 
to humans, animals, or plants; (iii) the 
vector consists of DNA fi"om exempt 
host- vector systems (see Appendix C), 
fi'om plants of the same or closely 
related species, from nonpathogenic 
prokaryotes or nonpathogenic lower 
eukaryotic plants, from plants 
pathogens only if sequences resulting in 
production of disease symptoms have 
been deleted, or chimeric vectors 
constructed from sequences of exempt 
host-vector systems (see Appendix C) or 
from sequences from plant pathogens in 
which the disease symptoms have been 
deleted. The DNA may be introduced by 
any suitable method. If sequences 
resulting in production of disease 
symptoms are retained for purposes of 
Introducing the DNA into the plant, 
greenhouse-grown plemts must be 
shown to be free of such sequences 
before such plants, their derivatives, or 
seed can be used in field tests; (iv) 
plants are grown in controlled access 
fields under specified conditions 
appropriate for the plant under study 
and the geographical location. Such 
conditions should include provisions 
for using good cultural and pest control 
practices, for physical isolation from 
plants of the same species outside of the 
experimental plot in accordance with 
pollination characteristics of the . 
species, and the prevention of plants 
containing recombinant DNA from 
becoming established in the 
environment. Review by the 
Institutional Biosafety Committee 
should include an appraisal by 
scientists knowledgeable of the crop, its 
production practices, and the local 
geographical conditions. Procedures for 
assessing alterations in and the spread 
of organisms containing recombinant 
DNA must be developed. The results of 
the outlined tests must be submitted for 
review and approval by the Institutional 
Biosafety Committee. Copies of such 
results must be submitted to the Office 
of Recombinant DNA Activities, 
National Institutes of Health, Building 
31, Room 4B11, Bethesda, Maryland 
20892, (301) 496-9838. 
Appendix M. Points to Consider in the 
D^ign and Submission of Protocols for 
the Transfer of Recombinant DNA 
Molecules Into the Genome of One or 
More Human Subjects 
Appendix M applies to research 
conducted at or sponsored by an 
institution that receives any support for 
recombinant DNA research from the 
NIH. Researchers not covered by the 
NIH Guidelines are encouraged to use 
Appendix M. Experiments in which 
recombinant DNA or DNA or RNA 
derived from recombinant DNA is 
introduced into one or more human 
subjects with the intent of stably 
modifying his/her genome are covered 
by Sections III-A-2, III-B-2, and III-B- 
3 (see Section V-U). Experiments in 
which recombinant DNA or DNA or 
RNA derived from recombinant DNA 
and that are not covered by Sections III- 
A-2, III-B-2, or III-B-3 and that are not 
considered exempt under Section V-U, 
are covered under Section III-0-7. 
This document is intended to provide 
guidance in preparing proposals for NIH 
consideration imder Sections IlI-A-2 
and ni-B-2. Section III^A-2 addresses 
Major Actions involving the transfer of 
recombinant DNA or DNA or RNA 
derived from recombinant DNA into one 
or more human subjects that have been 
determined by NIH/ORDA, in 
consultation with the RAC Chair and 
one or more RAC members, as 
necessary, to: (i) Represent novel 
characteristics (e.g., target disease or 
vector), (ii) represent an uncertain 
degree of risk to hum^ health or the 
environment, or (iii) contain 
information determined to require 
further public review. Proposals 
considered under Section III-A-2 will 
be reviewed by the RAC and approved 
by the NIH Director. RAC review of 
experiments considered under Section 
ni-A-2 will follow publication of a 
precis of the proposal in the Federal 
Register and an opportunity for public 
comment. Section III-B-2 addresses 
Minor Actions involving the transfer of 
recombinant DNA or DNA or RNA 
derived from recombinant DNA into one 
or more human subjects that have been 
determined by NIH/ORDA, in 
consultation with the RAC Chair and 
one or more RAC members, as 
necessary, to qualify for the Accelerated 
Review process. Proposals considered 
under Sections III-A-2 and III-B-2 will 
be on a case-by-case basis. A list of 
actions approved imder Sections III-A- 
2 and 111-^2 involving the transfer of 
recombinant DNA or DNA or RNA 
derived from recombinant DNA into one 
or more human subjects is available 
from the Office of Recombinant DNA 
Activities, National Institutes of Health, 
Building 31, Room 4B11, Bethesda, 
Maryland 20892, (301) 496-9838. The 
list of actions to the NIH Guidelines 
involving the transfer of recombinant 
DNA or DNA or RNA derived from 
recombinant DNA into one or more 
human subjects does not include 
experiments considered to be exempt 
from RAC and NIH/ORDA review under 
Section III-C-7. 
Since the recombinant DNA or DNA 
or RNA derived from recombinant DNA 
is expected to be confined following 
transfer to one or more human subjects, 
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