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Federal Register / Vol. 45, No. 72 / Friday, April 11, 1980 / Notices 
DEPARTMENT OF HEALTH, 
EDUCATION, AND WELFARE 
National Inatltutea of Health 
Recombinant DNA Reaearch; Physical 
Containment Recommendations for 
Large-Scale Uses of Organlams 
Containing Recombinant DNA 
Molecules 
AGENCY: National Institutes of Health 
(NIH), HEW. 
ACTION: Publication of physical 
containment recommendations for large- 
scale uses of organisms containing 
recombinant DNA molecules. 
SUMMARY: These physical containment 
recommendations for large-scale uses of 
organisms containing recombinant DNA 
molecules are published for public 
information in accordance with the 
recommendation of the NIH . 
Recombinant DNA Advisory Committee. 
FOR FlfttTHER INFORMATION CONTACT: 
Dr. W. Emmett Barkely, Director, 
Division of Safety, Building 13, Room 
2E45, National Institutes of Health, 
Bethesda, Maryland 20205. 
SUPPLEMENTAL INFORMATION: The NIH 
Guidelines for Research Involving 
Recombinant DNA Molecules (45 FR 
6724, January 29, 1980) specify in Section 
IV— E— 1— b— (3)— (d) that the Director, NIH, 
is responsible for "authorizing, under 
procedures specified by the RAC, large- 
scale experiments (i.e., involving more 
than 10 liters of culture) for recombinant 
DNAs that are rigorously characterized 
and free of harmful sequences.” 
At its September 6-7, 1979, meeting, 
the NIH Recombinant DNA Advisory 
Committee (RAC) adopted (by a vote of 
14 in favor, none opposed, and 3 
abstentions) procedures to be followed 
in reviewing such large-scale 
experiments. These procedures included 
the submission by the applicant of 
certain information including “a 
description of the applicant's laboratory 
practices, containment equipment, and 
facilities rlevant to the containment of 
large volumes of culture." - 
At its May 21-23, 1979, meeting, the 
RAC approved (by a vote of 19 in favor, 
none opposed, and no abstentions) the 
creation of a working group to "examine 
physical containment requirements for 
large-scale experiments and that a 
document should be prepared.” 
At its December 6-7, 1979, meeting, 
the RAC reviewed Draft Physical 
Containment Guidelines for Large-Scale 
Uses of Organisms Containing 
Recombinant DNA Molecules and voted 
(15 in favor, none opposed, and no 
abstentions) that additional comments 
be solicited on the draft standards. 
At its March 6-7, 1980, meeting, the 
RAC reviewed Draft Physical 
Containment Guidelines for Large-Scale 
Use of Organisms Containing 
Recombinant DNA Molecules which had 
been revised from the earlier draft, 
based upon comments received. 
Following considerable discussion at the 
meeting, a motion was passed (with 16 
in favor, 2 opposed, and 1 abstention) 
that the document be published in the 
Federal Register. 
The document which is now published 
in the Federal Register contains changes 
from that reviewed by the RAC on 
March 7, 1980, based upon suggestions 
made at the March 7 meeting. These 
changes are: — (1) To eliminate what was 
Section VII-C-8 in the draft reviewed by 
the RAC on March 7, 1980; Section VII- 
D-6 which consists of identical text has 
been retained. — (2) To change the 
phrase "using a non-debilitated strain of 
the host organisms used in the research 
or production process" to "using the 
organism that will serve as the host for 
propagating the recombinant DNA 
molecules" in Section VH-B-2, VII-B-5, 
vn-c-2, vn-c-5, vn-c-8, vh-d-2, vn- 
D-5, and VB-D-9. 
When earlier drafts of this document 
had been prepared it was proposed that 
it might eventually be formally 
promulgated as Part VII of the NIH 
Guidelines for Research Involving 
Recombinant DNA Molecules. It has not 
in fact been formally adopted as Part VII 
of the NIH Guidelines. The format has, 
however, been retained in this Draft 
Part VII. This document, while not 
formally part of the NIH Guidelines, can 
serve as a model for those preparing 
submissions to the NIH under the NIH 
Guidelines. 
The document now published in the 
Federal Register is endorsed by the NIH 
Division of Safety as physical 
containment recommendations 
appropriate for large-scale uses of 
organisms containing recombinant DNA 
molecules: 
Dated: March 31, 1980. 
Donald 8. Fredrickson, 
Director, National Institutes of Health. 
Draft Part VTI of the NIH Guidelines for 
Research Involving Recombinant DNA 
Molecules 
VII. Physical Containment for Large- 
Scale Uses of Viable 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 all large-scale research 
or production activities approved by the 
Director, NIH in accordance with 
Sections IV-E-2-b-(l)-(e) and IV-E-1- 
b— (3)— (d) of the NIH Guidelines. 
All provisions of the NIH Guidelines 
shall apply to large-scale research or 
production activities with the following 
modifications: 
• Part VII shall replace Section II— B 
when quantities in excess of 10 liters of 
culture are involved in research or 
production. 
• 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-D-4. 
• The institution shall establish and 
maintain a health surveillance program 
for personnel engaged in large-scale 
research or production activities 
involving viable organisms containing 
recombinant DNA molecules which 
require P3 containment at the laboratory 
scale. The program shall include: 
preassignment and periodic physical 
and medical examinations; collection, 
maintenance and analysis of serum 
specimens for monitoring serologic 
changes that may result from the 
employee’s work experience; and 
provisions for the investigation of any 
serious, unusual or extended illnesses of 
employees to determine possible 
occupational origin. 
VII-A. Selection of Physical 
Containment Levels. The selection of 
the physical containment level required 
for recombinant DNA research or 
production involving more than 10 liters 
of culture is based on the containment 
guidelines established in Part III of the 
Guidelines. For purposes of large-scale 
research or production, three physical 
containment levels are established. 
These are referred to as Pl-LS, P2-LS, 
and P3-LS. The Pl-LS level of physical 
containment is required for large-scale 
research or production of viable 
organisms containing recombinant DNA 
molecules which require PI containment 
at the laboratory scale. The P2-LS level 
of physical containment is required for 
large-scale research or production of 
viable organisms containing 
recombinant DNA molecules which 
require P2 containment at the laboratory 
scale. The P3-LS level of physical 
containment is required for large-scale 
research or production of viable 
organisms containing recombinant DNA 
molecules which require P3 containment 
at the laboratory scale. No provisions 
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