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Federal Register / Vol. 47, No. 102 / Wednesday. May 26. 1982 / Notices 
Appendix B-Ul-B — Animal Disease 
Or^anisma and Vector* Which are 
Forbidden Entry into the United State* 
by USOA Policy 
Appendix B-UI-C — Organism* Which May 
Not Be Studied in the United States 
Except At SpeciRed Facilities 
Appendix B-IV — Footnote* and Reference* 
of Appendix B 
Appendix C Exemptions Under UI-D-5 
Appendix C-l — Recombinant DNAs in 
Tissue Culture 
Appendix C-Q — Experiment* Involving £. 
co/I K-12 Host-Vector System* 
Appendix C-IU — Experiments Involving 
Saccharomyc9» c»nvisiae Ho*t-Vector 
Systems 
Appendix C-IV — Experiments Involving 
BaciJJua $ubtills Host-Vector Systems 
Appendix C-V — Footnotes and References 
of Appendix C 
Appendix 0. Actions Taken Under the 
Guidelines 
Appendix E. Certified Host-Vector Systems 
Appendix F. Containment Conditions for 
Qoning of Gene* Coding for the 
Biosynthesis of Molecules Toxic for 
Vertebrates 
Appendix F-l — General Information 
Appendix F-41 — Containment Conditions 
for Goning of Toxic Molecule Genes in 
£ coh K-12 
Appendix F-m — Containment Conditions 
for Cloning of Toxic Molecule Genes in 
Organisms Other than £ co/i K-12 
Appendix F-IV — SpeciBc Approvals 
Appendix G. Physical Containment 
Appendix G-1 — Standard Practice* and 
Training 
Appendix G-H — Physical Containment 
Levels 
Appendix G-O-A — Pi Level 
Appendix G-O-A-1 — Laboratory Practices 
Appendix G-O-A-2 — Containment 
^uipment 
Appendix C-D-A-3— Special Laboratory 
Design 
Appendix G-O-B— P2 Level 
Appendix G-O-B-1 — Laboratory Practices 
Appendix G-U-B-2 — Containment 
^uipment 
Appendix G-O-B-3— Special Laboratory 
Design 
Appendix C-D-C — P3 Level 
Appendix G-O-C-1 — Laboratory Practice* 
Appendix G-tt-C-2 — Containment 
^ulpment 
Appendix G-O-C-3— Special Laboratory 
Design 
Appendix C-O-D — P4 Level 
Appendix G-O-D-l — Laboratory Practices 
Appendix G-O-D-2 — Containment 
^uipmeot 
Appendix G-O-D-3 — Special Laboratory 
Design 
Appendix C-IU — Footnote* and References 
of Appendix C 
Appendix H. Shipment 
Appendix I. Biological Containment 
Appendix I-l — Levels of Biological 
Containment 
Appendix H-A — HVl 
Appendix l-l-A-1 — EKl 
Appendix I-4-A-2— Other HVl 
Appendix I-l-B— HV2 
Appendix I-O — Certification of Host- 
Vector Systems 
Appendix I-Il-A — Responsibility 
Appendix I-Il-B — Data To Be Submitted 
for Certification 
Appendix I-U-B-1 — HVl Systems Other 
than £ coJi K-12 
Appendix l-U-B-2 — HV2 Systems 
Appendix 1-111 — Footnotes and References 
of Appendix 1 
I. Scope of the Guidelines 
I-A. Purpose. The purpose of these 
Guidelines is to specify practices for 
constructing and handling (i) 
recombinant DNA molecules and (ii) 
organisms and viruses containing 
recombinant DNA molecules. 
I-B. Definition of Recombinant DNA 
Molecules. In the context of these 
Guidelines, recombinant DNA molecules 
are defined as either (i) molecules which 
are constructed outside living cells by 
joining natural or synthetic DNA 
segments to DNA molecules that can 
replicate in a living cell, or (ii) DNA 
molecules that result from the 
replication of those described in (i) 
alMve. 
Synthetic DNA segments likely to 
yield a potentially harmful 
polynudeotide or polypeptide (e.g.. a 
toxin or a pharmacologically active 
agent) shall be considered as equivalent 
to their natural DNA counterpart. If the 
synthetic DNA segment is not expressed 
in vivo as a biologically active 
polynucleotide or polypeptide product, it 
is exempt from the Guidelines. 
I-C. General Applicability. The 
Guidelines are applicable to all 
recombinant DNA research within the 
United States or its territories which is 
conducted at or sponsored by an 
Institution that receives any support for 
recombinant DNA research from NIH. 
This includes research performed by 
NIH directly. 
An individual receiving support for 
research involving recombinant DNA 
must be assodated with or sponsored 
by an Institution that can and does 
assume the responsibilities assigned in 
these Guidelines. 
The Guidelines are also applicable to 
projects done abroad if they are 
supported by NIH funds. If the host 
country, however, has established rules 
for the conduct of recombinant DNA 
projects, then a certificate of compliance 
with those rules may be submitted to 
NIH in lieu of compliance with the NIH 
Guidelines. NIH reserves the right to 
withhold funding if the safety practices 
to be employed abroad are not 
reasonably consistent with the NIH 
Guidelines. 
I-D. General Definitions. The 
following terms, which are used 
throughout the Guidelines, are defined 
as follows; 
IV-D-1. "Institution" means any 
public or private entity (including 
Federal. State, and local government 
agencies). 
I-D-2. "Institutional Biosafety 
Committee” or "IBC" means a 
committee that (i) meets the 
requirements for membership specified 
in Section IV-B-2. and (ii) reviews, 
approves, and oversees projects in 
accordance with the responsibilities 
defined in Sections IV-^2 and IV-B-3. 
I-D-3. "NIH Office of Recombinant 
DNA Activities" or "ORDA” means the 
office within NIH with responsibility for 
(i) reviewing and coordinating all 
activities of NIH related to the 
Guidelines, and (ii) performing other 
duties as defined in Section IV-C-3. 
I-D-4. "Recombinant DNA Advisory 
Committee” or "RAC" means the public 
advisory committee that advises the 
Secretary, the Assistant Secretary for 
Health, and the Director of the National 
Institutes of Health concerning 
recombinant DNA research. "Hie RAC 
shall be constituted as specified in 
Section IV-C-2. 
I-D-5. "Director. NIH" or "Director" 
means the Director of the National 
Institutes of Health or any other officer 
or employee of NIH to whom authority 
has been delegated. 
II. Containment 
Effective biological safety programs 
have been operative in a vaHety of 
laboratories for many years. 
Considerable information, therefore, 
already exists for the design of physical 
containment facilities and the selection 
of laboratory procedures applicable to 
organisms carrying recombinant DNAs 
(3-16). The existing programs rely upon 
mechanisms thaL for convenience, can 
be divided into two categories: (i) A set 
of standard practices that are generally 
used in microbiological laboratories, 
and (ii) special procedures, equipment, 
and laboratory installations that provide 
physical barriers which are applied in 
varying degrees according to the 
estimated biohazard. 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. 
Experiments on recombinant DNAs. 
by their vary nature, lend themselves to 
a third containment mechanism — 
namely, the application of highly 
specific biological barriers. In fact, 
natural barriers do exist which limit 
either (i) the infectivity of a vector, or 
vehicle, (plasmid or virus) for specific 
hosts or (ii) its dissemination and 
survival in the environment. The vectors 
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