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Federal Register / Vol. 59. No. 127 / Tuesday, July 5, 1994 / Notices 
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 III-B-2 and Appendix M-V) 
and will be considered as Minor Actions 
(see Section IV-C-l-b-(2)-(aJ). 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 NHH Director approval and only 
require registration with NIH/ORDA 
(see Section III-C-7). 
Section I-B. Definition of Recombinant 
DNA Molecules 
In the context of the NIH Guidelines, 
recombinant DNA molecules are 
defined as either: (i) Molecules that are 
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 pharmacologically 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 
poly’nucleotide 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-l-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 
practiqes that are employed abroad must 
be reasonably consistent with the NIH 
Guidelines. 
Section I-D. General Definitions 
The following terms, which are used 
throughout the NIH Guidelines, are 
defined as follows: 
Section I-D-1. 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 I-D-3. The ‘Office of 
Recombinant DNA Activities (ORDA)’ is 
the office within the NIH that is 
responsible for: (i) Reviewing and 
coordinating all activities relating to the 
NIH Guidelines, and (ii) performing 
other duties as defined in Section IV-C- 
3. 
Section I-D-^. The ‘Recombinant 
DNA Advisory Committee’ is the public 
advisory committee that advises the 
Department of Health and Human 
Services (DHHS) Secretary, the DHHS 
Assistant Secretary for Health, and the 
NIH Director concerning recombinant 
DNA research. The RAC shall be 
constituted as specified in Section IV-C- 
2. 
Section I-D-5. The ‘NIH Director' is 
the Director of the National Institutes of 
Health, or any other officer or employee 
of NIH to whom authority has been 
delegated. 
Section I-D-6. ‘Deliberate release’ is 
defined as a planned introduction of 
recombinant DNA-containing 
microorganisms, plants, or animals into 
the environment. 
B. Amendment to Section II, 
Containment, of the NIH Guidelines 
The amended version of Section II 
reads as follows: 
Section II. Containment 
Effective biological safety programs 
have been operative in a variety of 
laboratories for many years. 
Considerable information already exists 
about the design of physical 
containment facilities and selection of 
laboratory' procedures applicable to 
organisms carrying recombinant DNA 
(see Section V-A). The existing 
programs rely upon mechanisms that 
can be divided into two categories: (i) A 
set of standard practices that are 
generally used in microbiological 
laboratories; and (ii) special procedures, 
equipment, and laboratory installations 
that provide physical barriers that are 
applied in varying degrees according to 
the estimated biohazard. Four biosafety 
levels are described in Appendix G. 
These biosafety levels consist of 
combinations of laboratory' practices 
and techniques, safety equipment, and 
laboratory' facilities appropriate for the 
operations performed and are based on 
the potential hazards imposed by the 
agents used and for the laboratory 
function and activity. Biosafety Level 4 
provides tlie most stringent containment 
conditions. Biosafety Level 1 the least 
stringent. 
Experiments involving recombinant 
DNA lend themselves to a third 
containment mechanism, namely, the 
application of highly specific biological 
barriers. Natural barriers exist that limit 
either: (i) The infectivity of a vector or 
vehicle (plasmid or virus) for specific 
hosts, or (ii) its dissemination and 
survival in the environment. Vectors, 
which provide the means for 
recombinant DNA and/or host cell 
replication, can be genetically designed 
to decrease, by many orders of 
magnitude, the probability of 
dissemination of recombinant DNA 
outside the laboratory (see Appendix I). 
Since these three means of 
containment are complementary, 
different levels of containment can be 
established that apply various 
combinations of the physical and 
biological barriers along with a constant 
use of standard practices. Categories of 
containment are considered separately 
in order that such combinations can be 
conveniently expressed in the NIH 
Guidelines. 
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