Federal Register / Vol. 59, No. 127 / Tuesday, July 5, 1994 / Notices 
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Appendix M-V. Procedures to be Followed 
for Accelerated Review of Human Gene 
Transfer Experiments by NIH/ORDA 
under Section ni-B-2 
Appendix M-Vl. Procedures to be Followed 
for Expedited Review of Single Patient 
Human Gene Transfer Experiments by 
the NIH Director Under S^tion IIl-A-2 
Appendix M-Vll. Footnotes of Appendix M 
App>endix P. Physical and Biological 
Containment for Recombinant DNA 
Research Involving Plants 
App>endix P-I. General Plant Biosafety Levels 
App)endix P-Il. Physical Containment Levels 
Appendix P-Il-A. Biosafety Level 1 — Plants 
(BLl-P) 
App>endix P-B-B. Biosafetv Le\’el 2 — Plants 
(BL2-P) 
Appendix P-II-C Biosafety Level 3 — Plants 
(BL3-P) 
Appendix P-II-D. Biosafety Level 4 — Plants 
(BL4-P) 
Appendix P-IU. Biological Containment 
Practices 
App>endix P-IIT-A. Biological Co.nlainment 
Practices (Plants) 
Appendix P-III— B. Biological Containment 
Practices (Microorganisms) 
App>endix P-IU-C Biological Containment 
Practices (Macroorganisms) 
Appendix Q. Physical and Biological 
Containment for Recombinant DNA 
Research Involving Animals 
Appendix Q-L General Considerations 
Appendix Q-I-A. Containment Levels 
Appjendix Q-l-B. Disposal of Animals (BLl- 
N through BL4-N) 
App>endix Q-II. Physical and Biological 
Containment Levels 
Appendix Q-U-A. Biosafety Level 1 — 
Animals (BLl-N) 
App>endix Q-D-B. Biosafety Level 2 — 
Animals (BL2-N) 
Appendix Q-H-C. Biosafety Level 3 — 
Animals (BL3-N) 
App)endix Q-4I-D. Biosafety Level 4 — 
Animals (BL4-N) 
Appendix Q-fll. Footnotes and References 
for Appendix Q 
Section I. Scope of the Nlli Guidelines 
Section I-A. Purpose 
The purpose of the NIH Guidelines is 
to specify practices for constructing and 
handling: (i) Recombinant 
deoxyribonucleic acid (DNA) molecules, 
and (ii) organisms and viruses 
containing recombinant DNA 
molecules. 
Section I-A-1. Any recombinant DNA 
expieriment, which according to the NIH 
Guidelines requires approval by the 
NIH. must be submitted to the NIH or 
to another Federal agency that has 
jurisdiction for review and approval. 
Once approval, or other applicable 
clearances, has been obtained from a 
Federal agency other than the NIH 
(whether the experiment is referred to 
that agency by tlie NIH or sent directly 
there by the submitter), the experiment 
may proceed without the necessity for 
NIH review or approval (see exceptions 
in Sections I-A-2 and I-A-3). 
Section I-A-2. Certain experiments 
that involve the deliberate transfer of 
recombinant DNA or DNA or RNA 
derived from recombinant DNA into one 
or more human subjects (see Section V- 
U) shall be considered Major Actions 
(see Section rV-C-l-b-(l)), and shall 
require RAC review and NIH Director 
approval, if determined by NIH/ORDA 
in consultation with the RAC Chair and/ 
or 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 human health or the 
environment, or (iii) contain 
information determined to require 
further public review (see Section III- 
A-2). 
Section I-A-3. Experiments involving 
the transfer of recombinant DNA to one 
or more human subjects that are not 
considered under Section III-A-2 may 
qualify for Accelerated Review (see 
Section IIl-B-2 and Appendix M-V) 
and will be considered as Minor Actions 
(see Section IV-C-l-b-(2)-(a))- Actions 
that qualify for Accelerated Review will 
be reviewed and approved by NIH/ 
ORDA in consultation with the RAC 
Chair and/or one or more RAC 
members, as necessary. 
Certain experiments involving the 
transfer of recombinant DNA or DNA or 
RNA derived from recombinant DNA 
into one or more human subjects (see 
Section V— U) may be considered exempt 
from RAC and/or NIH/ORDA review 
and/or NIH Director approval and only 
require registration with NIH/ORDA 
(see Section III-C-7). 
Section 1-B. Definition of Recombinant 
DNA Molecules 
In the context of the NIH GuideUnes, 
recombinant DNA molecules are 
defined as either: (i) Molecules that cue 
constructed outside living cells by 
joining natural or synthetic DNA 
segments to DNA molecules that can 
replicate in a living cell, or (ii) 
molecules that result from the 
replication of those described in (i) 
above. 
Synthetic DNA segments which are 
likely to yield a potentially harmful 
polynucleotide or polypeptide (e.g., a 
toxin or a pharmacologic^ly active 
agent) are considered as equivalent to 
their natural DNA counterpart. If the 
synthetic DNA segment is not expressed 
in vivo as a biologically active 
polynucleotide or polypeptide product, 
it is exempt from the NIH Guidelines. 
Genomic DNA of plants and bacteria 
that have acquired a transposable 
element, even if the latter was donated 
from a recombinant vector no longer 
present, are not subject to the NIH 
Guidelines unless the transposon itself 
contains recombinant DNA. 
Section I-C. General Applicability 
Section I-C-1. The NIH Guidelines 
are applicable to: 
Section I-C-l-a. All recombinant 
DNA research within the United States 
(U.S.) or its territories that is conducted 
at or sponsored by an institution that 
receives any support for recombinant 
DNA research from the NIH, including 
research performed directly by the NIH. 
An individual who receives support for 
research involving recombinant DNA 
must be associated with or sponsored by 
an institution that assumes the 
responsibilities assigned in the NIH 
Guidelines. 
Section I-C-l-b. All recombinant 
DNA research performed abroad: 
Specifically: 
Section I-C— 1— b-{l). Research 
supported by NIH funds. 
Section I-C-l-b-(2). If they involve 
testing in humans of materials 
containing recombinant DNA developed 
with NIH funds and if the institution 
that developed those materials sponsors 
or participates in those projects. 
Participation includes research 
collaboration or contractual agreements, 
not mere provision of research 
materials. 
Section I-C-l-b-(3). If the host 
country has established rules for the 
conduct of recombinant DNA research, 
then the research must be in compliance 
with those rules. If the host country 
does not have such rules, the proposed 
research must be reviewed and 
approved by an NIH-approved 
Institutional Biosafety Committee or 
equivalent review body and accepted in 
writing by an appropriate national 
governmental authority of the host 
country. The safety practices that are 
employed abroad must be reasonably 
consistent with the NIH Guidelines. 
Section 1-D. General Definitions 
The following terms, which are used 
throughout tlie NIH Guidelines, are 
defined as follows: 
Section 1-D-l. An "institution" is any 
public or private entity (including 
Federal, state, and local government 
agencies). 
Section I-D-2. An "Institutional 
Biosafety Committee" is a committee 
that: (i) Meets the requirements for 
membership specified in Section IV-B- 
2, and (ii) reviews, approves, and 
oversees projects in accordance with the 
responsibilities defined in Section IV— 
B-2. 
Section l-D-3. The "Office of 
Recombinant DNA Activities (ORDA) ’ 
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