Federal Register / Vol. 59, No. 127 / Tuesday. July 5, 1994 / Notices 
34475 
Physical containment conditions 
within laboratories, described in 
Appendix G, may not always be 
appropriate for all organisms because of 
their physical size, the number of 
organisms needed for an experiment, or 
the particular growth requirements of 
the organism. Likewise, biological 
containment for microorganisms 
described in Appendix 1 may not be 
appropriate for all organisms, 
particularly higher eukaryotic 
organisms. However, significant 
information exists about the design of 
research facilities and experimental 
procedures that are applicable to 
organisms containing recombinant DNA 
that is either integrated into the genome 
or into microorganisms associated with 
the higher organism as a symbiont, 
pathogen, or other relationship. This 
information describes facilities for 
physical contaiiiment of organisms used 
in non-traditional laboratory settings 
and special practices for limiting or 
excluding the unwanted establishment, 
transfer of genetic information, and 
dissemination of organisms beyond the 
intended location, based on both 
physical and biological containment 
principles. Research conducted in 
accordance with these conditions 
effectively confines the organism. 
For research involving plants, four 
biosafety levels (BLl-P through BL4-P) 
are described in Appendix P. BLl-P is 
designed to provide a moderate level of 
containment for experiments for which 
there is convincing biological evidence 
that precludes the possibility of 
survival, transfer, or dissemination of 
recombinant DNA into the environment, 
or in which there is no recognizable and 
predictable risk to the environment in 
the event of accidental release. BL2-P is 
designed to provide a greater level of 
containment for experiments involving 
plants and certain associated organisms 
in which there is a recognized 
possibility of survival, transmission, or 
dissemination of recombinant DNA 
containing organisms, but the 
consequence of such an inadvertent 
release has a predictably minimal 
biological impact. BL3-P and BL4-P 
describe additional containment 
conditions for research with plants and 
certain pathogens and other organisms 
that require special containment 
t«ecause of their recognized potential for 
signifif;ant detrimental impact on 
managed or natural ecosystems. BLl-P 
relic's upon accepted scientific practices 
for conducting research in most 
ordinary greenhouse or growth chamber 
facilities and incorporates accepted 
pro<,edures for good pest control and 
cultural praclK es BLl-P facilities and 
procedures provide a modified and 
protected environment for the 
propagation of plants and 
microorganisms associated with the 
plants and a degree of containment that 
adequately controls the potential for 
release of biologically viable plants, 
plant parts, and microorganisms 
associated with them. BL2-P and BL3- 
P rely upon accepted scientific practices 
for conducting research in greenhouses 
with organisms infecting or infesting 
plants in a manner that minimizes or 
prevents inadvertent contamination of 
plants within or surrounding the 
greenhouse. BL4-P describes facilities 
and practices known to provide 
containment of certain exotic plant 
pathogens. 
For research involving animals, which 
are of a size or have growth 
requirements that preclude the use of 
conventional primary containment 
systems used for small laboratory 
animals, four biosafety levels (BLl-N 
through BL4-N) are described in 
Appendix Q. BLl-N describes 
containment for animals that have been 
modified by stable introduction of 
recombinant DNA, or DNA derived 
therefrom, into the germ-line (transgenic 
animals) and experiments involving 
viable recombinant DNA-modified 
microorganisms and is designed to 
eliminate the possibility of sexual 
transmission of the modified genome or 
transmission of recombinant DNA- 
derived viruses known to be transmitted 
from animal parent to offspring only by 
sexual reproduction. Procedures, 
practices, and facilities follow classical 
methods of avoiding genetic exchange 
between animals. BL2-N describes 
containment which is used for 
transgenic animals associated with 
recombinant DNA-derived organisms 
and is designed to eliminate the 
possibility of vertical or horizontal 
transmission. Procedures, practices, and 
facilities follow classical methods of 
avoiding genetic exchange between 
animals or controlling arthropod 
transmission. BL3-N and BL4-N 
describe higher levels of containment 
for research with certain transgenic 
animals involving agents which pose 
recognized hazard. 
In constructing the NIH 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. These definitions do 
not take into account all existing and 
anticipated information on special 
procedures that will allow particular 
experiments to be conducted under 
different conditions than indicated here 
without affecting risk Individual 
investigators and Institutional Biosafety 
Committees are urged to devise simple 
and more effective containment 
procedures and to submit recommended 
changes in the NIH Guidelines to permit 
the use of these procedures.” 
C. Amendment to Section III, 
Experiments Covered by the NIH 
Guidelines 
The previous version of Section Ill-A- 
2 will be deleted as follows: 
Section III-A-2. Deliberate release 
into the environment of any organism 
containing recombinant DNA except 
those listed below. The term ‘deliberate 
release’ is defined as a planned 
introduction of recombinant DNA- 
containing microorganisms, plants, or 
animals into the environment. 
Section Ill-A-2-a. Introduction 
conducted under conditions considered 
to be accepted scientific practices in 
which there is adequate evidence of 
biological and/or physical control of the 
recombinant DNA-containing 
organisms. The nature of such evidence 
is described in Appendix L. 
Section IIl-A-2-b. Deletion derivatives 
and single base changes not otherwise 
covered by the NIH Guidelines. 
Section lll-A-2-c. For 
extrachromosomal elements and 
microorganisms (including viruses), 
rearrangements and amplifications 
within a single genome. Rearrangements 
involving the introduction of DNA from 
different strains of the same species 
would not be covered by this 
exemption.” 
The amended version of Section 111 
reads as follows: 
Section 111. Experiments Covered by 
the NIH Guidelines. 
This section describes five categories 
of experiments involving recombinant 
DNA: (i) Those that require R-^C review 
and NIH and Institutional Biosafety 
Committee approval before initiation 
(see Section III-A), (ii) those that require 
NIH/ORDA and Institutional Biosafety 
Committee approval before initiation 
(see Section 111-B); (iii) those that require 
Institutional Biosafety Committee 
approval before initiation (see Section 
Ill-C), (iv) those that require 
Institutional Biosafety Committee 
notification simultaneous with 
initiation (see Section III-D), and (v) 
those that are exempt from the NIH 
Guidelines (see Section Ill-E). 
Note: If an experiment falls into cither 
Section III-A or Section III-B and ore of l.he 
other categories, the rules pertaining to 
Section III-A or Section Ill-B shall bo 
followed. If an experiment falls into Sectioii 
Ill-E and into cither Sections Ill-C or MI D 
categories as well, the experiment is 
considered exempt from the NIH Ciiideliii' 
Recombinant DNA Research, Volume 19 
[676] 
