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Federal Register J Vol. 59, No. 162 / Tuesday, August 23, 1994 / Notices 
“Section I-A-l. Any recombinant 
DNA experiment, 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 the NIH or sent directly 
there by the submitter), the experiment 
may proceed without the necessity for 
NIH review or approval (see exception 
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 IV-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 HI— 
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 
HI-A-2 may qualify for Accelerated 
Review (see Section IH-B-2 and 
Appendix M-V) and will be considered 
as Minor Actions (see Section IV-C-1- 
b— (2) — Ca)). 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 l-A is proposed to read: 
“Section L Scope of the NIH. 
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-rA-1. If a recombinant DNA 
experiment requiring NIH approval is 
also subject to review and approval by 
another Federal agency, the proposed 
experiment must be submitted to the 
other Federal agency. Once approval, or 
other applicable clearances, has been 
obtained from a Federal agency other 
than the NIH, the experiment may 
proceed without the necessity for NIH 
review or approval, except as provided 
in Section I-A-l-a. 
“Section I-A-l-a. Experiments 
involving the deliberate transfer of 
recombinant DNA or DNA or RNA 
derived from recombinant DNA into one 
or more human subjects shall be 
submitted directly to the Food and Drug 
Administration (FDA). Such proposals 
shall be submitted to the Director of the 
Division of Cellular and Gene 
Therapies, Office of Therapeutics 
Research and Review, Center for 
Biologies Evaluation and Research, 
Food and Drug Administration, 1401 
Rockville Pike, HFM-515, Rockville, 
Maryland 20852-1448, (301) 496-4709. 
Upon receipt, FDA will transmit all 
human gene transfer protocols to the 
NIH Office of Recombinant DNA 
Activities (ORDA). Simultaneously with 
the FDA review, NIH/ORDA will 
evaluate the protocol for possible RAC 
review. Whenever possible. Principal 
Investigators will be notified within 15 
working days following receipt of the 
submission whether RAC review will be 
required. RAC reviewed applications 
will be forwarded to reviewers 8 weeks 
prior to the next quarterly RAC meeting. 
Factors that may contribute to the need 
for RAC review include: (i) novel 
approaches, (ii) new diseases, (iii) 
unique applications of gene transfer, 
and (iv) other issues that may require 
further public review. The RAC’s 
recommendations, including specific 
requirements and stipulations, will be 
forwarded to the NIH Director. The NIH 
Director’s final recommendation will be 
forwarded to the FDA Commissioner.” 
Section in (Experiments Covered by the 
NIH Guidelines), paragraph 1, currently 
reads: 
“This section describes five categories 
of experiments involving recombinant 
DNA: (i) those that require RAC review 
and NIH and Institutional Biosafety 
Committee approval before 
initiation. . , 
Section III, paragraph 1, is proposed to 
read: 
“This section describes five categories 
of experiments involving recombinant 
DNA: (i) those that require Institutional 
Biosafety Committee approval, RAC 
review, and NIH Director consideration 
before initiation. . . 
Section III-A currently reads: 
“Section EQ-A. Experiments that 
Require Institutional Biosafety 
Committee Approval, RAC Review, and 
NIH Approval Before Initiation 
“Experiments in this category are 
considered Major Actions (see Section 
IV- C-l-b-fl)) cannot be initiated 
without submission of relevant 
information on the proposed experiment 
to the Office of Recombinant DNA 
Activities, National Institutes of Health, 
Building 31, Room 4B11, Bethesda, 
Maryland 20892, (301) 496-9838, the 
publication of the proposal in the 
Federal Register for 15 days of 
comment, review by the RAC, and 
specific approval by the NIH (not 
applicable for Expedited Review single 
patient human gene transfer 
experiments considered under 
Appendix M-VI). The containment 
conditions for such experiments will be 
recommended by the RAC and set by 
the NIH at the time of approval. Such 
experiments require Institutional 
Biosafety Committee approval before 
initiation. Specific experiments already 
approved are included in Appendix D 
which may be obtained from the Office 
of Recombinant DNA Activities, 
National Institutes of Health, Building 
31, Room 4B11, Bethesda, Maryland 
20892, (301) 496-9838. 
“Section EQ-A-1 . Deliberate transfer 
of a drug resistance trait to 
microorganisms that are not known to 
acquire the trait naturally (see Section 
V- B), if such acquisition could 
compromise the use of the drug to 
control disease agents in humans, 
veterinary medicine, or agriculture. 
“Section m-A-2. Certain experiments 
involving 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 IV-C-l-b-(l) and 
Appendix M-HI), and shall require RAC 
review and NIH Director approval, if 
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 human health or the 
environment, or (iii) contain 
information determined to require 
further public review. The requirement 
for RAC review shall not be considered 
to preempt any other required review or 
approval of experiments with one or 
more human subjects. Relevant 
Institutional Biosafety Committee and 
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Recombinant DNA Research, Volume 20 
