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Federal Register / Vol. 59, No. 127 / Tuesday, July 5, 1994 ./ Notices 
Section III-B-3. Minor Modifications to 
Human Gene Transfer Experiments 
A minor modification in a human 
gene transfer protocol is a modification 
that does not significantly alter the basic 
design of the protocol and that does not 
increase risk to human subjects or the 
environment. After approval has been 
obtained by the relevant Institutional 
Biosafety Committee and Institutional 
Review Board, NIH/ORDA will consider 
the change in consultation with the RAC 
Chair and one or more RAC members, 
as necessary. Submit minor 
modifications to the Office of 
Recombinant DI^A Activities, National 
Institutes of Health, Building 31, Room 
4B11, Bethesda, Maryland 20892, (301) 
496-9838. The RAC Chair will provide 
a report on any such approvals at the 
next regularly scheduled RAC meeting. 
Section IH-C. Experiments that Require 
Institutional Biosafety Committee 
Approval Before Initiation 
Prior to the initiation of an 
experiment that falls into this category, 
the Principal Investigator must submit a 
registration document to the 
Institutional Biosafety Committee which 
contains the following information; (i) 
The 60 urce(s) of DNA; (ii) the nature of 
the inserted DNA sequences; (iii) the 
hostfs) and vector(s) to be used; (iv) if 
an attempt will be made to obtain 
expression of a foreign gene, and if so, 
indicate the protein that will be 
produced; and fv) the containment 
conditions that will be implemented as 
specified in the NIH Guidelines. For 
experiments in this category, the 
registration document shall be dated, 
signed by the Principal Investigator, and 
filed with the Institutional Biosafety 
Committee. The Institutional Biosafety 
Committee shall review andapprow all 
experiments in this category prior to 
their initiation. Requests to decrease the 
level of containment specified for 
experiments in this category will be 
considered by NIH (see Section IV-C-1- 
b-(2)-(c)). 
Section IIl-C-1. Experiments Using 
Human or Animal Pathogens (Class 2, 
Class 3, Class 4, or Class 5 Agents (see 
Section V-A) as Host-Vector Systems 
Section Ul-C-l-a. Experiments 
involving the introduction of 
recombinant DNA into Class 2 agents 
shall be conducted at Biosafety Level 
(BL) 2 containment. Exp>eriments with 
such agents shall be conducted with 
whole animals at BL2 or BL2-N 
(Animals) containment. 
Section lll-C-l-b. Experiments 
involving the introduction of 
recombinant DNA into Class 3 agents 
shall be conducted at BL3 containment. 
Experiments with such agents shall be 
conducted with whole animals at BL3 or 
BL3-N containment. 
Section fll-C-l-c. Experiments 
involving the introduction of 
recombinant DNA into Class 4 agents 
shall be conducted at BL4 containment. 
Experiments with such agents shall be 
conducted whtli whole animals at BL4 or 
BL4-N containtnent. 
Section Ill-C-l-d. Containment 
conditions for experiments involving 
the introduction of recombinant DNA 
into Class 5 agents shall be set on a case- 
by-case basis following NIH/ORDA 
review. A U.S. Department of 
Agriculture permit is required for work 
with Class 5 agents (see Sections V-R 
and V-T). Experiments with such agents 
shall be conducted with whole animals 
at BL4 or BL4-N containment. 
Section ni-C-2. Experiments in Which 
DNA From Human or Animal Pathogens 
(Class 2, Class 3, Class 4, or Class 5 
Agents (see Section V-A) is Cloned Into 
Nonpathogenic Prokaryotic or Lower 
Eukaryotic Host-Vector Systems 
Section III-C-2-a. Experiments in 
which DNA from Class 2 or Class 3 
agents (see Section V-A) is transferred 
into nonpathogenic prokaryotes or 
lower eukaryotes may be performed 
under BL2 cxmtainment. Experiments in 
which DNA from Class 4 agents is 
transferred into nonpathogenic 
prokaryotes or lower eukaryotes may be 
performed under BL2 containment after 
demonstration that only a totally and 
irreversibly defective fraction of the 
agent’s genome is present in a given 
recombinant. In the absence of such a 
demonstration, BL4 containment shall 
be used. The Institutional Biosafety 
Committee may approve the specific 
lowering of containment for particular 
experiments to BLl. Many experiments 
in this category are exempt from the 
NIH Guidelines (see Section fU-E). 
Experiments Involving the formation of 
recombinant DNA for certain genes 
coding for molecules toxic for 
vertebrates require NIH/ORDA approval 
(see Section III-B-1) or shall be 
conducted under NIH specified 
conditions as described in Appendix F. 
Section IU-C-2-b. Containment 
conditions for experiments in which 
DNA from Class 5 agents is transferred 
into nonpathogenic prokaryotes or 
lower eukaryotes shall be determined by 
NIH/ORDA following a case-by-case 
review. A U.S. Department of 
Agriculture permit is required for work 
with Class 5 agents fsee Sections V-R 
and V-T). 
Section III-C-3. E.xperknents Involving 
the Use of Infectious Animal or Plant 
DNA or RNA Viruses or Defective 
Animal or Plant DNA or RNA Viruses in 
the Presence of Helper Virus in Tissue 
Culture Systems 
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 
vectors under conditions that permit a 
productive infection. In such cases, 
serious consideration should be given to 
increasing physical containment by at 
least one level. 
Note; Recombinant DNA or RNA molecules 
derived therefrom, which contain less than 
two-thirds of the genome of any eukaryotic 
virus (all viruses from a single Family (see 
Section V-Q) being considered identical (see 
Section V-S), are considered defective and 
may be used in the absence of helper under 
the conditions specified in Section lII-D-1. 
Section ni-G-3-a. Experiments 
involving the use of infectious or 
defective Class 2 animal viruses (see 
Section V-A, Appendix B-II, and 
Appendix B-II-E) in the presence of 
helper virus may be conducted at BL2. 
Siection fH-C-3-b. Experiments 
involving the use of infectious or 
defective Class 3 animal viruses (see 
Section V-A and Appendix B-IH-D) in 
the presence of helper virus may be 
conducted at BL3. 
Section III-C-3 -c. Experiments 
involving the use of infectious or 
defective Class 4 animal viruses (see 
Section V-A and Appendix B-IV-DJ in 
the presence of helper virus may be 
conducted at BL4. 
Section III-C-3-d. Experiments 
involving the use of infectious or 
defective Class 5 viruses (see Section V- 
A and Appendix B-V) in the presence of 
helper virus shall be determined on a 
case-by-case basis following NIH/ORDA 
review. A U.S. Department of 
Agriculture permit is required for work 
with Class 5 agents (see Sections V-R 
and V-T).. 
Section UI-C-3-e. Experiments 
involving the use of infectious or 
defective animal or plant viruses in the 
presence of helper virus are not covered 
in Sections ITI-C— 3-a through Ill-C— 3-d 
and may be conducted at BLl. 
Section IlI-C-4. Experiments Involving 
Whole Animals 
This section covers experiments 
involving whole animals in which the 
animal’s genome has been altered by 
stable introduction of recombinant 
DNA, or DNA derived therefrom, into 
Recombinant DNA Research, Volume 19 
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