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Federal Register / Vol. 46, No. 11X5 / Wednesday. June 1, 1963 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Guidelines for Research Involving 
Recombinant DNA Molecules; June 
1983 
These NIH guidelines supersede 
earlier versions and will be in effect 
until further notice. 
Table of Contents 
I. Scope of the Guidelines 
l-A Purpose 
l-D Defintion of Recombinant DNA 
Molecules 
l-C General Applicability 
l-U General Definitions 
II. Containment 
III. Containment Guidelines for Covered 
F.xperiments 
1II-A Experiments that Require RAC 
Review and NIH and IBC Approval 
Before Initiation 
lll-B Experiments that Require IBC 
Approval Before Initiation 
1 1 1— B — 1 Experiments Using I luman or 
Animal Pathogens (Class 2, Class 3. 
Class 4. or Class 5 Agents) as Host- 
Vector Systems 
Ill-El-2 Experiments in Which DNA from 
Human or Animal Pathogens (Class 2. 
Class 3. Class 4. or Class 5 Agents) is 
Cloned in Nonpathogenic Prokaryotic or 
Lower Eukaryotic Host-Vector Systems 
III-B-3 Experiments Involving the Use of 
Infectious Animal or Plant Viruses or 
Defective Animal or Plant Viruses in the 
Presence of Helper Virus in Tissue 
Culture Systems 
lll-B— 4 Recombinant DNA Experiments 
Involving Whole Animals or Plants 
1 1 1— B — 5 Experiments Involving More than 
10 1-iters of Culture 
III-C Experiments that Require IBC 
Notice Simultaneously with Initiation of 
Experiments 
III— IT Exempt Experiments 
IV. Roles and Responsibilities 
IV- A Policy 
IV-B Responsibilities of the Institution 
IV-B-1 General Information 
IV-B-2 Membership and IVooedures of 
the IBC 
IV-B-3 Functions of the IBC 
IV-B— 4 Biological Safety Officer 
IV-B-5 Principal Investigator 
lV-B-5-a PI — General 
IV-B-5-b Submissions by the PI to NIH 
IV-B-5-c Submissions bv the PI to the 
IBC 
IV-B-5— d PI Responsibilities Prior to 
Initiating Research 
IV-b-5-e PI Responsibilities During the 
Conduct of the Research 
IV-C Responsibilities of Nil I 
I V— C— 1 Director 
IV-C-l-a Ceneral Responsibilities of the 
Director, NIH 
IV-C-l-b Specific Responsibilities of the 
Director. NIH 
IV-C-2 Recombinant DNA Advisory 
Committee 
IV-C-3 The Office of Recombinant DNA 
Activities 
IV'— C— 1 Other NIH Components 
1V-D Compliance 
V. Footnotes and References of Sections 1—1 V 
VI. Voluntary Compliance 
Vl-A Basic Policy 
Vl-B IBC Approval 
VI-C Certification of Host-Vector 
Systems 
Vl-D Requests for Exemptions and 
Approvals 
Vl-E Protection of Proprietary Data 
Appendix A. Exemptions Under III-D— 4 
Appendix B. Classification of 
Microorganisms on the Basis of Hazard 
Appendix B-l Classification of Eliologic 
Agents 
Appendix B-l-A Class 1 Agents 
Appendix B-l-B Class 2 Agents 
Appendix B-I-B-l Bacterial Agents 
Appendix B-I-B-2 Fungal Agents 
Appendix B-l-B-3 Parasitic Agents 
Appendix B— I— B — 4 Viral. Rickettsial, and 
Chlamydial Agents 
Appendix B-l-C Class 3 Agents 
Appendix B-I-C-l Bacterial Agents 
Appendix B-l-C-2 Fungal Agents 
Appendix B-l-C-3 Parasitic Agents 
Appendix B-I-C-4 Viral. Rickettsial, and 
Chlamydial Agents 
Appendix B-I-D Class 4 Agents 
Appendix B-I-D-l Bacteriul Agents 
Appendix B-I-D-2 Fungal Agents 
Appendix B-l-D-3 Parasitic Agents 
Appendix B-I-D— 4 Viral. Rickettsial, and 
Chlamydial Agents 
Appendix B— II Classification of 
Oncogenic Viruses on the Basis of 
Potential Hazard 
Appendix B-II-A Low-Risk Oncogenic. 
Viruses 
Appendix B— 1 1— B Moderate-Risk 
Oncogenic Viruses 
Appendix B — III Class 5 Agents 
Appendix B — II I— A Animal Disease 
Organisms Which are Forbidden Entry 
into the United States by Law 
Appendix B-III-B Animal Disease 
Organisms and Vectors Which are 
Forbidden Entry into the United Stales 
by USDA Policy 
Appendix B-III-C Organisms Which May 
Not Be Studied in the United States 
Except At Specified Facilities 
Appendix B-IV Footnotes and References 
of Appendix B 
Appendix C. Exemptions Under 111— D— 5 
Appendix C-l Recombinant DNAs in 
Tissue Culture 
Appendix C-II Experiments Involving E. 
co!i K-12 Host-Vector Systems 
Appendix C— III Experiments Involving 
Succharomyces cerevisiae I losl-Vector 
Systems 
Appendix C-IV Experiments Involving 
Bacillus subti/is Host-Vector Systems 
Appendix C-V Footnotes and References 
of Appendix C 
Appendix D. Actions Taken Under the 
Guidelines 
Appendix F.. Certified Host-Vector Systems 
Appendix F. Containment Conditions for 
Cloning of Genes Coding for the 
Biosynthesis of Molecules Toxic for 
Vertebrates 
Appendix F-l General Information 
Appendix F-II Containment Conditions 
for Cloning of Toxic Molecule Genes in 
F co/i K-12 
Appendix K— III Containment Conditions 
for Cloning of Toxic Molecule Genes in 
Organisms Other than E. Coll K-12 
Appendix F-IV Specific Approvals 
Appendix G. Physical Containment 
Appendix G-l Standard Practices and 
Training 
Appendix Cl—ll Physical Containment 
Levels 
Appendix G-ll-A PI I.evel 
Appendix C-ll-A-1 Laboratory Practices 
Appendix G-II-A-2 Containment 
Equipment 
Appendix G-ll-A-3 Speciul Laboratory 
Design 
Appendix G — II— B P2 Level 
Appendix G-ll-B-1 Laboratory Practices 
Appendix G-II-B-2 Containment 
Equipment 
Appendix G-ll-B-3 Special laboratory 
Design 
Appendix G-ll-C P3 Level 
Appendix G-II-C-1 laboratory Practices 
Appendix G-II-C-2 Containment 
Equipment 
Appendix G-Il-C-3 Special Laboratory 
Design 
Appendix C-ll-D P4 Level 
Appendix G-II-D-1 Laboratory I*raclices 
Appendix G-II-D-2 Containment 
Equipment 
Appendix G-ll-D-3 Special Laboratory 
Design 
Appendix G — 1 1 f Footnotes and References 
of Appendix G 
Appendix H. Shipment 
Appendix I. Biological Containment 
Appendix 1-1 levels of Biological 
Containment 
Appendix I— I— A fIVl 
Appendix I-l-A-1 HVl 
Appendix l-l-A-2 Other EK1 
Appendix l-l-B HV2 
Appendix I— II Certification of Host- 
Vector Systems 
Appendix I— II— A Responsibility 
Appendix I— II— B Data To Be Submitted 
for Certification 
Appendix l-Il-B-1 HVl Systems Other 
than E. coli K-12 
Appendix I-Il-B-2 HV2 Systems 
Appendix I— 1 1 1 Footnotes and References 
of Appendix I 
Appendix J. Federal Interagency Advisory 
Committee on Recombinant DNA 
Research 
Appendix J-I Federal Interagency 
Advisory Committee 
Appendix J— II Footnote of Appendix ) 
Appendix K. Physical Containment for Large- 
Scale Uses of Organisms Containing 
Recombinant DNA Molecules 
Appendix K-l Selection of Physical 
Containment Levels. 
Appendix K-ll Pl-LS Level 
Appendix K— III P2-I.S Level 
Appendix K-IV P3-LS Level 
Appendix L. Release into the Environment of 
Certain Plants 
Appendix l^l General Information 
Appendix L-ll Criteria Allowing Review 
by the RAC Plant Working Croup 
Without the Requirement for Full RAC 
Review 
Appendix I/-III Specific Approvals 
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