Federal Register / Vol. 48, No. 100 / Wednesday. June 1. 1983 / Notices 
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I. Scope of the Guidelines 
I-A. Purpose. The purpose of these 
Guidelines is to specify practices for 
constructing and handling (i) 
recombinant DNA molecules and (ii) 
organisms and viruses containing 
recombinant DNA molecules. 
I-B. Definition of Recombinant DNA 
Molecules. In the context of these 
Guidelines, recombinant DNA molecules 
are defined as either (i) molecules which 
are constructed outside living cells by 
joining natural or synthetic DNA 
segments to DNA molecules that can 
replicate in a living cell, or (ii) DNA 
molecules that result from the 
replication of those described in (i) 
above. 
Synthetic DNA segments likely to 
yield a potentially harmful 
polynucleotide or polypeptide (e.g., a 
toxin or a pharmacologically active 
agent) shall be 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 Guidelines. 
I-C. General Applicability. The 
Guidelines are applicable to all 
recombinant DNA research within the 
United States or its territories which is 
conducted at or sponsored by an 
Institution that receives any support for 
recombinant DNA research from NIH. 
This includes research performed by 
NIH directly. 
An individual receiving support for 
research involving recombinant DNA 
must be associated with or sponsored 
by an Institution that can and does 
assume the responsibilities assigned in 
these Guidelines. 
The Guidelines are also applicable to 
projects done abroad if they are 
supported by NIH funds. If the host 
country, however, has established rules 
for the conduct of recombinant DNA 
projects, then a certificate of compliance 
with those rules may be submitted to 
NIH in lieu of compliance with the NIH 
Guidelines. NIH reserves the right to 
withhold funding if the safety practices 
to be employed abroad are not 
reasonably consistent with the NIH 
Guidelines. 
I-D. General Definitions. The 
following terms, which are used 
throughout the Guidelines, are defined 
as follows: 
I-D-l. "Institution" means any public 
or private entity (including Federal, 
State, and local government agencies). 
l-D-2. "Institutional Biosafety 
Committee" or “IBC" means 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 Sections IV-B-2 and IV-B-3. 
I-D-3. "NIH Office of Recombinant 
DNA Activities” or "ORDA" means the 
office within NIH with responsibility for 
(i) reviewing and coordinating all 
activities of NIH related to the 
Guidelines, and (ii) performing other 
duties as defined in Section IV-C-3. 
I-D— 4. "Recombinant DNA Advisory 
Committee" or "RAC" means the public 
advisory committee that advises the 
Secretary, the Assistant Secretary for 
Health, and the Director of the National 
Institutes of Health concerning 
recombinant DNA research. The RAC 
shall be constituted as specified in 
Section IV-C-2. 
I-D-5. "Director, NIH" or "Director" 
means the Director of the National 
Institutes of Health or any other officer 
or employee of NIH to whom authority 
has been delegated. 
II. Containment 
Effective biological safety programs 
have been operative in a variety of 
laboratories for many years. 
Considerable information, therefore, 
already exists for the design of physical 
containment facilities and the selection 
of laboratory procedures applicable to 
organisms carrying recombinant DNAs 
[3-16]. The existing programs rely upon 
mechanisnrls that, for convenience, can 
be divided into two categories: (1) A set 
of standard practices that are generally 
used in microbiology laboratories, and 
(ii) special procedures, equipment, and 
laboratory installations that provide 
physical barriers which are applied in 
varying degrees according to the 
estimated biohazard. Four levels of 
physical containment, which are 
designated as Pi, P2, P3, and P4 are 
described in Appendix G. P4 provides 
the most stringent containment 
conditions. Pi the least stringent. 
Experiments on recombinant DNAs, 
by their very nature, lend themselves to 
a third containment mechanism — 
namely, the application of highly 
specific biological barriers. In fact, 
natural barriers do exist which 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. The vectors 
that provide the means for replication of 
the recombinant DNAs and/or the host 
cells in which they replicate can be 
genetically designed to decrease by 
many orders of magnitude the 
probability of dissemination of 
recombinant DNAs outside the 
laboratory. Further details on biological 
containment may be found in Appendix 
I. 
As these means of containment are 
complementary, different levels of 
containment appropriate for 
experiments with different recombinants 
can be established by applying various 
combinations of the physical and 
biological barriers along with a constant 
use of the standard practices. We 
consider these categories of 
containment separately in order that 
such combinations can be conveniently 
expressed in the Guidelines. 
In constructing the Guidelines, it was 
necessary to defined boundary 
conditions for the different levels of 
physical and biological containment and 
for the classes of experiments to which 
they apply. We recognize that these 
difinitions do not take into account all 
existing and anticipated information on 
special procedures that will allow 
particular experiments to be carried out 
under different conditions than 
indicated here without affecting risk. 
Indeed, we urge that individual 
investigators devise simple and more 
effective containment procedures and 
that investigators and institutional 
biosafety comittees recommend changes 
in the Guidelines to permit their use. 
III. Containment Guidelines for Covered 
Experiments 
Part III discusses experiments 
involving recombinant DNA. These 
experiments have been divided into four 
classes: 
III— A. Experiments which require 
specific RAC review and NIH and IBC 
approval before initiation of the 
experiment; 
III— B. Experiments which require IBC 
approval before initiation of the 
experiment; 
IIIII— C. Experiments which require 
IBC notification at the time of initiation 
of the experiment; 
III— D. Experiments which are exempt 
from the procedures of the Guidelines. 
If an experiment falls into both class 
III— A and one of the other classes, the 
rules pertaining to Class III— A must be 
followed. If an experiment falls into 
class III— D and into either class II I— B or 
III— C as well, It can be considered 
exempt from the requirements of the 
Guidelines. 
Changes in containment levels from 
those specified here may not be 
instituted without the express approval 
of the Director, NIH. (See Sections IV- 
C-l-b-{l), I V-C-l-b— (2). and 
subsections.) 
I II— A. Experiments that Require RAC 
Review and NIH and IOC Approval 
Before Initiation. Experiments in this 
category cannot be initiated without 
submission of relevant information on 
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