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Federal Register / Vol. 48, No. 44 / Friday. March 4. 1983 / Notices 
Waitz said industry believes such an 
action would provide a more efficient 
mechanism for further comment or 
change to the Recommendations. He 
expressed industry's concern that failure 
to take such action may leave a 
perceived gap in the overall regulatory 
scheme thereby encouraging the 
development of conflicting regulatory 
requirements. 
The Large-Scale Review Working 
Croup, which met on October 20, 1982, 
forwarded this proposal to the RAC and 
to the Working Group on Revision of the 
Guidelines without comment. 
The Working Group on Revision of the 
Guidelines, at its January 21, 1983, 
meeting, recommended incorporation 
into the Guidelines of the Physical 
Containment Recommendations for 
Large-Scale Uses of Organisms 
Containing Recombinant DNA 
Molecules. If the RAC recommends this 
action, editiorial modifications to revise 
and update sections of the Physical 
Containment Recommendations will be 
necessary. The proposed incorporation 
of the Physical Containment 
Recommendations into the Guidelines 
as a new Appendix K, requires all 
sections be renumbered. Minor editorial 
changes will be introduced throughout 
the document to reflect the 
modifications Introduced into the 
Guidelines since the Recommendations 
were published in April 1980. Proposed 
changes within the text are enumerated 
below. Readers should note that 
sections in the Recommendations which 
contain proposed revisions are 
identified by their current Section 
numbering. The proposed modified 
language is identified by new section 
numbering. The revised Large-Seal 
Recommendations are reprinted in their 
entirety at the end of this section. 
A. Section VII. Physical Containment 
for Large-Scale Uses of Organisms 
Containing Recombinant DNA 
Molecules 
1. Section VII would become 
Appendix K. 
2. The language of the first paragraph 
would be modified. It currently reads: 
This part of the NIH Guidelines specifies 
physical containment guidelines for large- 
scale (greater than 10 liters of culture) 
research or production involving viable 
organisms containing recombinant DNA 
molecules. It shall apply to all large-scale 
research or production activities approved by 
the Director, NIH, in accordance with 
Sections IV- E-2-b-jl)-(el and IV-E-l-b-{3)- 
(d) of the NIH Guidelines. 
That paragraph would be modified to 
read as follows: 
This part of the NIH Guidelines specifies 
physical containment guidelines for large- 
scale (greater than 10 liters of culture) 
research or production involving viable 
organisms containing recombinant DNA 
molecules. It shall apply to large-scule 
research or production activities as specified 
in Section III-B-5 of the Guidelines. 
3. The third paragraph (first bullet) 
will be modified to read: 
Appendix K shall replace Appendix G 
when quantities in excess of 10 liters of 
culture are involved in research or 
production. 
4. An editorial modification, 
substituting "Section IV-B-4" for 
"Section IV-D-4," will be introduced 
into the third paragraph of the 
Introduction. That paragraph will be 
modified to read: 
The institution shall appoint a biological 
safety officer if it engages in large-scale 
research or production activities involving 
viable organisms containing recombinant 
DNA molecules. The duties of the biological 
safety officer shall include those specified in 
Section IV-B-4 of the Guidelines. 
B. Section VII- A. Selection of Physical 
Containment Levels. 
This section will be renumbered as 
Appendix K-A. 
C. Section VI1-B. Pl-LS Level 
1. Section VII-B will be renumbered 
as Appendix K-B. 
2. Section VII-B-1 will be renumbered 
to Appendix K-B-l and an editorial 
modification will substitute Section 
"Appendix G-II-A” for “Section ll-B-1." 
The last sentence of Section VII-B-1 
will read: 
Volumes less than 10 liters may be handled 
outside of a closed system or other primary 
containment equipment provided all physical 
containment requirements specified in 
Appendix G-II-A of the Guidelines are met. 
3. Section VII-B-2 will be renumbered 
Appendix K-B-2 and an editorial 
modification will substitute "Appendix 
K-B-3" for the current "VII-B-3.” The 
first sentence of Section VII-B-2 would 
read: 
Appendix K-B-2. Culture fluids (except as 
allowed in Appendix K-B-3) shall not be 
removed from a closed system or other 
primary containment equipment unless the 
viable organisms containing recombinant 
DNA molecules have been inactivated by a 
validated inactivation procedure. 
4. In Section VII-B-6, an editorial 
modification will change the language to 
read: 
Appendix K-B-6. Emergency plans 
required by Section IV-B-3-f shall include 
methods and procedures for handling large 
losses of culture on an emergency basis. 
D. Section VII-C. P2-LS Level 
1. Section VII-C will be renumbered 
to Appendix K-C. 
2. Section VII— C— I will be renumbered 
Appenix K-C-l and in the last sentence 
of Section VII— C—l, an editorial 
modification will substitute "Appendix 
G-II-B" for the current "Section II— B— 2." 
3. Section VII-B-2 will be renumbered 
to Appendix K-C-2 and an editorial 
modification will substitute "Appendix 
K-C-3” for the current "VII-C-3." 
4. In Section VII-C-11, to be 
renumbered Appendix K-C-ll, an 
editorial modification will substitute 
"Section IV-B-3-f ' for the current 
“Section IV-D-3-d.” 
E. Section VI1-D. P3-LS Level 
1. Section VII-D will be renumbered 
to Appendix K-D. 
2. Section VII-D-1 will be renumbered 
to Section Appendix K-D-l and an 
editorial modification will substitute 
"Appendix G-II-C" for the current 
"Section II-B-3." 
3. Section VII-D-2 will be renumbered 
to Appendix K-D-2 and an editorial 
modification will substitute "Appendix 
K-D-3 for the current " IV-D-3." 
4. In Section VII-D-12, to be 
renumbered Appendix K-D-12, an 
editorial modification will substitute 
"Substitute IV-B-3-f ' for the current 
“Section IV-D-3-d." 
5. In Section VII-D-14-a, to be 
renumbered Apendix K-D-14a, an 
editorial modification will substitute 
“Appendix K-D-13a” for “Section VII— 
D-13-a.” 
Note. — In addition, if the Large-Scale 
Recommendations are incorporated into the 
Guidelines, the language of Secion III-B-5 of 
the Guidelines should also be modified as 
follows: 
III-B-5. Experiments Involving More Than 
10 Liters of Culture. The appropriate 
containment will be decided by the IBC. 
Where appropriate, Appendix K, Physical 
Containment for Large-Scale Uses of 
Organisms Containing Recombinant DNA 
Molecules, should be used. 
Proposed Appendix K 
Physical Containment for Large-Scale 
Uses of Organisms Containing 
Recombinant DNA Molecules 
This part of the NIH Guidelines 
specifies physical containment 
guidelines for large-scale (greater than 
10 liters of culture) research or 
production involving viable organisms 
containing recombinant DNA molecules. 
It shall apply to large-scale research or 
production activities as specified in 
Section III-B-5 of the NIH Guidelines. 
All provisions of the NIH Guidelines 
shall apply to large-scale research or 
production activities with the following 
modifications: 
