J4496 
Federal Register / Vol. 59, No. 127 / Tuesday, July 5, 1994 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Guidelines for Research Involving 
Recombinant DNA Molecules (NIH 
Guidelines) 
June 1994. 
These NIH Guidelines supersede all 
earlier versions and shall be in effect 
until further notice. 
Table of Contents 
Section I. Scope of the NIH Guidelines 
Section I-A. Purpose 
Section 1-B. Definition of Recombinant DNA 
Molecules 
Section 1-C. General Applicability 
Section I-D. General Definitions 
Section II. Containment 
Section in. Experiments Covered by the NIH 
Guidelines 
Section K-A. Experiments that Require 
Institutional Biosafety Committee 
Approval, RAC Review, and NIH 
Approval Before Initiation 
Section III-B. Experiments that Require NIH/ 
ORDA and Institutional Biosafety 
Committee Approval Before Initiation 
Section III-B-1. Experiments Involving the 
Cloning of Toxin Molecules with LDjo of 
Less than 100 Nanograms Per Kilogram 
Body Weight 
Section III-B-2. Accelerated Review of 
Human Gene Transfer Experiments 
Section IIl-B-3. Minor Modifications to 
Human Gene Transfer Experiments 
Section lU-C Experiments that Require 
Institutional Biosafety Committee 
Approval Before Initiation 
Section IIl-C-1. Experiments Using Human 
or Animal Pathogens (Class 2, Class 3, 
Class 4, or Class 5) Agents as Host-Vector 
Systems 
Section III-G-2. Experiments in which DNA 
from Human or Animal Pathogens (Class 
2, Class 3, Class 4, or Class 5) Agents is 
Cloned into Nonpathogenic Prokaryotic 
or Lower Eukaryotic Host-Vector 
Systems 
Section III-C-3. Experiments 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 
Section ni-C— 4 . Experiments Involving 
Whole Animals 
Section UI-C-5. Experiments Involving 
Whole Plants 
Section III-C-6. Experiments Involving More 
than 10 Liters of Culture 
Section ni-C-7. Human Gene Transfer 
Experiments Not Covered by Section III- 
A-2, ni-B-2, in-B-3, and Not 
Considered Exempt imder Section V-U 
Section m^. Experiments that Require 
Institutional Biosafety Committee Notice 
Simultaneous with Initiation 
Section III-D-1. Experiments Involving the 
Formation of Recombinant DNA 
Molecules Containing No More than 
Two-Thirds of the Genome of any 
Eukaryotic Virus 
Section III-D-2. Experiments Involving 
Whole Plants 
Section III-E. Exempt Experiments 
Section FV. Roles and Responsibilities 
Section IV-A. Policy 
Section IV-B. Responsibilities of the 
Institution 
Section IV-B-1. General Information 
Section IV-B-2. Institutional Biosafety 
Committee (IBC) 
Section IV-B-3. Biological Safety Officer 
(BSO) 
Section IV-B— 4. Principal Investigator (PI) 
Section IV-C. Responsibilities of the National 
Institutes of Health (NIH) 
Section FV-C-l. NIH Director 
Section IV-C-l-a. General Responsibilities 
Section IV-C-l-b. Specific Responsibilities 
Section rV-C-l-b-(l). Major Actions 
Section IV-C-l-b-{2). Minor Actions 
Section IV-C-2. Recombinant DNA Advisory 
Committee (RAC) 
Section IV-C-3. Office of Recombinant DNA 
Activities (ORDA) 
Section IV-C-4. Other NIH Components 
Section fV-D. Compliance with the NIH 
Guidelines 
Section FV-E. Voluntary Compliance 
Section V. Footnotes and References of 
Sections I-IV 
Appendix A. Exemptions under Section III- 
E-5 — Sublists of Nattiral Exchangers 
Appendix B. Classification of Etiologic 
Agents and Oncogenic Viruses on the 
Basis of Hazard 
Appendix B-I. Class 1 Agents 
Appendix B-II. Class 2 Agents 
Appendix B-III. Class 3 Agents 
Appendix B-IV. Class 4 Agents 
Appendix B-V. Class 5 Agents 
Apjjendix B-VI. Footnotes and References of 
Appendix B 
Appendix C. Exemptions under Section III- 
E— 6 
Appendix C-I. Recombinant DNA in Tissue 
Culture 
Appendix C-II. Escherichia coli K-12 Host- 
Vector Systems 
Appendix C-III. Sgccharomyces Host-Vector 
Systems 
Appendix C-IV. Bacillus subtilis or Bacillus 
licheniformis Host-Vector Systems 
Appendix C-V. Extrachrpmosomal Elements 
of Gram Positive Organisms' 
Appendix C-VI. Footnotes and References of 
Appendix C 
Appendix D. Major Actions Taken under the 
NIH Guidelines 
Appendix E. Certified Host-Vector Systems 
Appendix E-I. Bacillus subtilis 
Appendix E-Il. Saccharomyces cerevisiae 
Appendix E-HI. Escherichia coli 
Appendix E-FV. Neurospora crassa 
Appendix E-V. Streptomyces 
Appendix E-VI. Pseudomonas putida 
Appendix F. Containment Conditions for 
Cloning of Genes Coding for the 
Biosynthesis of Molecules Toxic for 
Vertebrates 
Appendix F-I. General Information 
Appendix F-II. Cloning of Toxin Molecule 
Genes in Escherichia coli K-12 
Appendix F-III. Cloning of Toxic Molecule 
Genes in Organisms other than 
Escherichia coli K-12 
Appendix F-IV. Specific Approvals 
Appendix G. Physical Containment 
Appendix G-I. Standard Practices and 
Training 
Appendix G-II. Physical Containment Levels 
Appendix G-Il-A. Biosafety Level 1 (BLl) 
Appendix G-II-B. Biosafety Level 2 (BL2) 
Appendix G-II-C. Biosafety Level 3 (BL3) 
Appendix G— II-D. Biosafety Level 4 (BL4) 
Appendix G-III. Footnotes and References of 
Appendix G 
Appendix H. Shipment 
Appendix I. Biological Containment 
Appendix l-I. Levels of Biological 
Containment 
Appendix 1-I-A. Host-Vector 1 Systems 
Appendix I-I-B. Host-Vector 2 Systems 
Appendix I-II. Certification of Host-Vector 
Systems 
Appendix I-III. Footnotes and References of 
Appendix I 
Appendix J. Biotechnology Research 
Subcommittee 
Appendix K. Physical Containment for Large 
Scale Uses of Organisms Containing 
Recombinant DNA Molecules 
Appendix K-I. Selection of Physical 
Containment Levels 
Appendix K-Il. Good Large Scale Practices 
(GLSP) 
Appendix K-Ill. Biosafety Level 1 (BLl) — 
Large Scale 
Appendix K-IV. Biosafety Level 2 (BL2) — 
Large Scale 
Appendix K-V. Biosafety Level 3 (BL3) — 
Large Scale 
Appendix K-VI. Footnotes of Appendix K 
Appendix K-VII. Definitions to Accompany 
Containment Grid and Appendix K 
Appendix L. Release into the Environment of 
Certain Plants 
Appendix M. Points to Consider in the 
Design and Submission of Protocols for 
the Transfer of Recombinant DNA 
Molecules into the Genome of One or 
More Human Subjects 
Appendix M-I. Description of Proposal 
Appendix M-I-A. Objectives and Rationale 
of the Proposed Research 
Appendix M-I-B. Research Design, 
Anticipated Risks and Benefits 
Appendix M-l-C. Selection of the Patients 
Appendix M-I-D. Informed Consent 
Appendix M-I-E. Privacy and 
Confidentiality 
Appendix M-II. Special Issues 
Appendix M-III. Guidelines for the 
Submission of Human Gene Transfer 
Protocols 
Appendix M-III-A. Principal Investigator- 
Submitted Material 
Appendix M-III-B. Time Frame for 
Submissions 
Appendix M-III-C. Oral Responses to the 
RAC 
Appendix M-III-D. Primary Reviewers’ 
Responses 
Appendix M-IV. Reporting Requirements 
Recombinant DNA Research, Volume 19 
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