Federal Register / Vol. 49, No. 227 / Friday. November 23, 1984 / Notices 
46267 
I. Scope of the Guidelines 
l-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 (eg., 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. 
l-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 the 
National Institutes of Health (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 N[H 
Guidelines. 
I-D. General Definitions. The 
following terms, which are used 
throughout the Guidelines, are defined 
as follows: 
l—D—1. ‘Institution” means any public 
or private entity (including Federal, 
State, and local government agencies). 
I-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 NLH related to the 
Guidelines, and (ii) performing other 
duties as defined in Section IV-C-3. 
l-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 NIH 
concerning recombinant DNA research. 
The RAC shall be constituted as 
specifed in Section IV-C-2. 
I-D-5. "Director, NIH" or "Director” 
means the Director of the NIH or any 
other officer or employee of NIH to 
whom authority has been delegated. 
IL 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 
(5-76). The existing programs rely upon 
mechanisms that, for convenience, 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 which are applied in 
varying degrees according to the 
estimated biohazard. Four biosafety 
levels (BL) are described in Appendix G. 
These bioaafety levels consist of 
combinations of laboratory practices 
and techniques, safety equipment, and 
laboratory facilities appropriate for the 
operations performed and the hazard 
posed by agents and for the laboratory 
function and activity. BL4 provides the 
most stringent containment conditions, 
BLl 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 three 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 these Guidelines, it 
was necessary to define 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 
definitions 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 IBCs recommend 
changes in the Guidelines to permit their 
use. 
III. 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 FAC review and NIH and IBC 
approval before initiation of the 
experiment; 
III-B. Experiments which require IBC 
approval before initiation of the 
experiment; 
III-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 IO-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 III— 
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), IV-C-l-b-(2), and subsections). 
III-A. Experiments that Require RAC 
Review and NIH and IBC Approval 
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