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Federal Register / Vol. 47, No. 102 / Wednesday, May 26, 1982 / Notices 
replication of malecules described in (i) 
above." 
Section IV-C-8 currently reads as 
follows; 
" ‘Federal Interagency Advisory 
Committee on Recombinant DNA 
Research' means the committee 
established in October 1976 to advise 
the Secretary, HHS, the Assistant 
Secretary for Health, and the Directory, 
NIH. on the coordination of those 
aspects of all Federal programs and 
activities which related to recombinant 
DNA research.” 
Section rV-C-9. the deRnition of 
Laboratory Safety Monograph would be 
moved to Appendix G. Physical 
Containment 
The text of current Section IV-<] 
would be renumbered to reflect its new 
position in I-D and the deletion of 
current sections IV-C-1, IV-C-2. and 
rv-c-e. 
2. Section II. Containment a. New 
language is added to the first paragraph 
of Section □. Containment as follows: 
"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." 
b. New language is added to the 
second paragraph of Section II. 
Containment as follows; 
“Further details on biological 
containment may be found in Appendix 
L" 
c. Section Il-A. Standard Practices 
and Training, would be moved to a new 
Appendix G and renumbered. 
d. Section U-B, Physical Containment 
Levels, would be moved to Appendix G 
and renumbered. 
e. The title of Tables I and II in 
Section II-B. "Combinations of 
Containment Safeguards.” would be 
changed to "Possible Combinations of 
Containment Safeguards." The tables 
would be moved to Appendix G. 
f. Section Il-C. Shipment would be 
moved to a new Appendix H and 
renumbered. Additional information on 
shipping procedures would be included. 
g. Section II-D, Biological 
Containment would be moved to a new 
Appendix I and renumbered. 
h. The language of item (vi) in the first 
paragraph of Section II-D-2-b-(2). HV2 
Systems, which would become 
Appendix I-Il-B-2, would be modified 
to read: 
"(vi) In some cases, the Investigator 
may be asked to submit data on survival 
and vector transmissibility from 
experiments in which the host-vector is 
fed to laboratory animals and human 
subjects. Such in vivo data may be 
required to confirm the validity of 
predicting in vivo survival on the basis 
of in vitro experiments." 
i. Section II-D-3. Distribution of 
Certified Host- Vectors, would be 
deleted. 
3. Section III. Containment Guidelines 
for Covered Experiments. 
a. Section IIl-A would be modified to 
read as follows: 
"lU-A. Experiments that Require RAC 
Review and NIH and IBC Approval 
Before Initiation. Experiments in this 
category cannot be initiated without 
submission of relevant information on 
the proposed experimept to NIH. the 
publication of the proposal in the 
Federal Register for thirty days of 
comment, review by the RAC, and 
specific approval by NIH. The 
containment conditions for such 
experiments %vill be recommended by 
RAC and set by NIH at the time of 
approval. Such experiments also require 
the approval of the IBC before initiation. 
Specific experiments already approved 
in this section and the appropriate 
containment conditions are listed in 
Appendices D and F. If an experiment is 
similar to those listed in Appendices D 
and F, ORDA may determine 
appropriate containment conditions 
according to case precedents under 
Section IV-C-l-b-{3)-{g)." 
b. Section IlI-A-1 would be modified 
to read as follows: 
"lIl-A-1. Deliberate formation of 
recombinant DNAs containing genes for 
the biosynthesis of toxic molecules 
lethal for vertebrates at an LDm of less 
than 100 nanograms per kilogram body 
weith (e g., microbial toxins such as the 
botulinum toxins, tetanus toxin, 
diphtheria toxin. Shigella dysenteriae 
neuro-toxin). Specific approval has been 
given for the cloning in E. coli K-12 of 
DNAs containing genes coding for the 
biosynthesis of toxic molecules which 
are lethal to vertebrates at 100 
nanograms to 100 micrograms per 
kilogram body weight. Containment 
levels for these experiments are 
specified in Appendix F." 
c. The title of Section III-B-1 would be 
modified to read as follows: 
"III-B-1. Experiments Using Human 
or Animal Pathogens (Class 2. Class 3, 
Class 4 , or Class 5 Agents fl]) as Host- 
Vector Systems. " 
d. Mention of CDC in Sections Ill-B- 
1-a, III-B-l-b, and III-B-l-c would be 
deleted. 
e. Section lU-B-l-c would be 
amended to read as follows; 
"llI-B-l-c. Experiments involving the 
introduction of recombinant DNA into 
Class 4 agents can be carried out at P4 
containment." 
f. A new Section 01-B-l-d would be 
added as follows: 
"IlI-B-l-d. Containment conditions 
for experiments involving the 
introduction of recombinant DNA into 
Class 5 agents will be set on a case-by- 
case basis following ORDA review. A 
USDA permit is required for work with 
Class 5 agents (18,20]" 
g. The title of Section III-B-2 would be 
modified to read as follows: 
"Ill-B-2. Experiments in Which DNA 
from Human or Animal Pathogens 
(Class 2, Class 3. Class 4. or Class 5 
Agents (Ij) is Cloned in Nonpathogenic 
Prokaryotic or Lower Eukaryotic Host- 
Vector Systems." 
h. Sections III-B-2-a and III-B-2-b 
would be combined into a single Section 
III-B-2-a as follows: 
"lIl-B-2-a. Recombinant DNA 
experiments in which DNA from Class 2 
or Class 3 agents (1) is transferred into 
nonpathogenic prokaryotes or lower 
eukaryotes may be performed under P2 
containment. Recombinant DNA 
experiments in which DNA from Class 4 
agents is transferred into nonpathogenic 
prokaryotes or lower eukaryotes can be 
performed at P2 containment after 
demonstration that only a totally and 
irreversibly defective fraction of the 
agent's viral genome is present in a 
given recombinant. In the absence of 
such a demonstration, P4 containment 
should be used. 
"Specific lowering of containment to 
Pi for particular experiments can be 
approved by the IBC. Many experiments 
in this category will be exempt from the 
Guidelines. (See Section III-D-4 and III- 
D-5.) Experiments involving the 
formation of recombinant DNAs for 
certain genes coding for molecules toxic 
for vertebrates require RAC review and 
NIH approval (see Section IIl-A-1), or 
must be carried out under NIH specified 
conditions as described in Appendix F." 
i. A new Section III-B-2-b dealing 
with Class 5 agents would be added as 
follows; 
"IU-B-2-b. Containment conditions 
for experiments in which DNA from 
Class 5 agents is transferred into 
nonpathogenic prokaryotes or lower 
eukaryotes will be determined by ORDA 
following a case-by-case review. A 
USDA permit is required for work with 
Class 5 agents [18,20].” 
j. A new paragraph would be added 
immediately after the heading of Section 
III-B-3 as follows: 
"Caution. — Special care should be 
used in the evaluation of containment 
levels for experiments which are likely 
to either enhance the pathogenicity (e.g., 
insertion of a host oncogene) or to 
extend the host range (e.g., introduction 
of novel control elements) of viral 
[435] 
