NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) - November 2013

NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) - November 2013

NIH GUIDELINES FOR RESEARCH

INVOLVING

RECOMBINANT OR SYNTHETIC

NUCLEIC ACID MOLECULES

(NIH GUIDELINES)

November 2013

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

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Visit the OBA Web site at:

http://oba.od.nih.gov

For current information on Guidelines, Protocols, Principal Investigators, Meetings,
and information about upcoming Gene Therapy Policy Conferences

These NIH Guidelines shall supersede all earlier versions until further notice.

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FEDERAL REGISTER NOTICES

Effective June 24, 1994, Published in Federal Register, July 5, 1994 (59 FR 34472)

Amendment Effective July 28, 1994, Federal Register, August 5, 1994 (59 FR 40170)

Amendment Effective April 17, 1995, Federal Register, April 27, 1995 (60 FR 20726)

Amendment Effective December 14, 1995, Federal Register, January 19, 1996 (61 FR 1482)

Amendment Effective March 1, 1996, Federal Register, March 12, 1996 (61 FR 10004)

Amendment Effective January 23, 1997, Federal Register, January 31, 1997 (62 FR 4782)

Amendment Effective September 30, 1997, Federal Register, October 14, 1997 (62 FR 53335)

Amendment Effective October 20, 1997, Federal Register, October 29, 1997 (62 FR 56196)

Amendment Effective October 22, 1997, Federal Register, October 31, 1997 (62 FR 59032)

Amendment Effective February 4, 1998, Federal Register, February 17, 1998 (63 FR 8052)

Amendment Effective April 30, 1998, Federal Register, May 11, 1998 (63 FR 26018)

Amendment Effective April 29, 1999, Federal Register, May 11, 1999 (64 FR 25361)

Amendment Effective October 2, 2000, Federal Register, October 10, 2000 (65 FR 60328)

Amendment Effective December 28, 2000 Federal Register, January 5, 2001 (66 FR 1146)

Amendment Effective December 11, 2001 Federal Register, December 11, 2001 (66 FR 64051)

Amendment Effective December 19, 2001 Federal Register, November 19, 2001 (66 FR 57970)

Amendment Effective January 10, 2002 Federal Register, December 11, 2001 (66 FR 64052)

Amendment Effective January 24, 2002 Federal Register, November 19, 2001 (66 FR 57970)

Amendment Effective September 22, 2009 Federal Register, September 22, 2009 (74 FR 48275)

Amendment Effective January 19, 2011 Federal Register, January 19, 2011 (76 FR 3150)

Amendment Effective May 12, 2011 Federal Register, May 12, 2011 (76 FR 27653)

Amendment Effective October 11, 2011 Federal Register, October 11, 2011 (76 FR 62816)

Amendment Effective February 21, 2013 Federal Register, February 21, 2013 (78 FR 12074)

Amendment Effective March 5, 2013 Federal Register, September 5, 2012 (77 FR 54584)

Amendment Effective November 6, 2013 Federal Register, November 6, 2013 (78 FR 66751)

                                                         

TABLE OF CONTENTS

SECTION I........................ SCOPE OF THE NIH GUIDELINES

Section I-A................... Purpose

Section I-B................... Definition of Recombinant and Synthetic Nucleic Acid Molecules

Section I-C................... General Applicability

Section I-D................... Compliance with the NIH Guidelines

Section I-E................... General Definitions

SECTION II....................... SAFETY CONSIDERATIONS

Section II-A.................. Risk Assessment

Section II-A-1................ Risk Groups

Section II-A-2................ Criteria for Risk Groups

Section II-A-3................ Comprehensive Risk Assessment

Section II-B.................. Containment

SECTION III...................... EXPERIMENTS COVERED BY THE NIH GUIDELINES

Section III-A.................. Experiments that Require Institutional Biosafety Committee Approval, RAC Review, and NIH Director Approval Before Initiation (See Section IV-C-1-b-(1), Major Actions).

Section III-A-1............... Major Actions under the NIH Guidelines

Section III-B.................. Experiments That Require NIH/OBA and Institutional Biosafety Committee Approval Before Initiation

Section III-B-1............... Experiments Involving the Cloning of Toxin Molecules with LD₅₀ of Less than 100 Nanograms per Kilogram Body Weight

Section III-B-2............... Experiments that have been Approved (under Section III-A-1-a) as Major Actions under the NIH Guidelines

Section III-C.................. Experiments that Require Institutional Biosafety Committee and Institutional Review Board Approvals and RAC Review Before Research Participant Enrollment

Section III-C-1............... Experiments Involving the Deliberate Transfer of Recombinant or Synthetic Nucleic Acid Molecules, or DNA or RNA Derived from Recombinant or Synthetic Nucleic Acid Molecules, into One or More Human Research Participants

Section III-D................. Experiments that Require Institutional Biosafety Committee Approval Before Initiation

Section III-D-1............... Experiments Using Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents as Host-Vector Systems (See Section II-A, Risk Assessment)

Section III-D-2............... Experiments in Which DNA From Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents is Cloned into Nonpathogenic Prokaryotic or Lower Eukaryotic Host-Vector Systems

Section III-D-3............... Experiments Involving the Use of Infectious DNA or RNA Viruses or Defective DNA or RNA Viruses in the Presence of Helper Virus in Tissue Culture Systems

Section III-D-4............... Experiments Involving Whole Animals

Section III-D-5............... Experiments Involving Whole Plants

Section III-D-6............... Experiments Involving More than 10 Liters of Culture

Section III-D-7............... Experiments Involving Influenza Viruses

Section III-E.................. Experiments that Require Institutional Biosafety Committee Notice Simultaneous with Initiation

Section III-E-1. ............. Experiments Involving the Formation of Recombinant or Synthetic Nucleic Acid Molecules Containing No More than Two-Thirds of the Genome of any Eukaryotic Virus

Section III-E-2............... Experiments Involving Whole Plants

Section III-E-3............... Experiments Involving Transgenic Rodents

Section III-F.................. Exempt Experiments

SECTION IV..................... 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-2-a........... Membership and Procedures

Section IV-B-2-b........... Functions

Section IV-B-3.............. Biological Safety Officer (BSO)

Section IV-B-4.............. Plant, Plant Pathogen, or Plant Pest Containment Expert

Section IV-B-5.............. Animal Containment Expert

Section IV-B-6.............. Human Gene Therapy Expertise

Section IV-B-7.............. Principal Investigator (PI)

Section IV-B-7-a........... General Responsibilities

Section IV-B-7-b........... Information to Be Submitted by the Principal Investigator to NIH OBA

Section IV-B-7-c........... Submissions by the Principal Investigator to the Institutional Biosafety Committee

Section IV-B-7-d........... Responsibilities of the Principal Investigator Prior to Initiating Research

Section IV-B-7-e........... Responsibilities of the Principal Investigator During the Conduct of the Research

Section IV-C................. Responsibilities of the National Institutes of Health (NIH)

Section IV-C-1.............. NIH Director

Section IV-C-1-a........... General Responsibilities

Section IV-C-1-b........... Specific Responsibilities

Section IV-C-1-b-(1)...... Major Actions

Section IV-C-1-b-(2)...... Minor Actions

Section IV-C-2.............. Recombinant DNA Advisory Committee (RAC)

Section IV-C-3.............. Office of Biotechnology Activities (OBA)

Section IV-C-4.............. Other NIH Components

Section IV-D................. Voluntary Compliance

Section IV-D-1.............. Basic Policy - Voluntary Compliance

Section IV-D-2.............. Institutional Biosafety Committee Approval - Voluntary Compliance

Section IV-D-3.............. Certification of Host-Vector Systems - Voluntary Compliance

Section IV-D-4.............. Requests for Exemptions and Approvals - Voluntary Compliance

Section IV-D-5.............. Protection of Proprietary Data - Voluntary Compliance

Section IV-D-5-a........... General

Section IV-D-5-b........... Pre-submission Review

SECTION V...................... FOOTNOTES AND REFERENCES OF SECTIONS I THROUGH IV

APPENDIX A.................... EXEMPTIONS UNDER SECTION III-F-6--SUBLISTS OF NATURAL EXCHANGERS

Appendix A-I................ Sublist A

Appendix A-II............... Sublist B

Appendix A-III............... Sublist C

Appendix A-IV.............. Sublist D

Appendix A-V............... Sublist E

Appendix A-VI.............. Sublist F

APPENDIX B.................... CLASSIFICATION OF HUMAN ETIOLOGIC AGENTS ON THE BASIS OF HAZARD

Appendix B-I................ Risk Group 1 (RG1) Agents

Appendix B-II............... Risk Group 2 (RG2) Agents

Appendix B-II-A............ Risk Group 2 (RG2) - Bacterial Agents Including Chlamydia

Appendix B-II-B............ Risk Group 2 (RG2) - Fungal Agents

Appendix B-II-C............ Risk Group 2 (RG2) - Parasitic Agents

Appendix B-II-D............ Risk Group 2 (RG2) - Viruses

Appendix B-III............... Risk Group 3 (RG3) Agents

Appendix B-III-A........... Risk Group 3 (RG3) - Bacterial Agents Including Rickettsia

Appendix B-III-B........... Risk Group 3 (RG3) - Fungal Agents

Appendix B-III-C........... Risk Group 3 (RG3) - Parasitic Agents

Appendix B-III-D........... Risk Group 3 (RG3) - Viruses and Prions

Appendix B-IV.............. Risk Group 4 (RG4) Agents

Appendix B-IV-A........... Risk Group 4 (RG4) - Bacterial Agents

Appendix B-IV-B........... Risk Group 4 (RG4) - Fungal Agents

Appendix B-IV-C........... Risk Group 4 (RG4) - Parasitic Agents

Appendix B-IV-D.......... Risk Group 4 (RG4) - Viral Agents

Appendix B-V............... Animal Viral Etiologic Agents in Common Use

Appendix B-V-1............ Murine Retroviral Vectors

APPENDIX C.................... EXEMPTIONS UNDER SECTION III-F-8

Appendix C-I................ Recombinant or Synthetic Nucleic Acid Molecules in Tissue Culture

Appendix C-I-A............. Exceptions

Appendix C-II............... Escherichia coli K-12 Host-Vector Systems

Appendix C-II-A............ Exceptions

Appendix C-III............... Saccharomyces Host-Vector Systems

Appendix C-III-A........... Exceptions

Appendix C-IV.............. Kluyveromyces Host-Vector Systems

Appendix C-IV-A........... Exceptions

Appendix C-V............... Bacillus subtilis or Bacillus licheniformis Host-Vector Systems

Appendix C-V-A........... Exceptions

Appendix C-VI.............. Extrachromosomal Elements of Gram Positive Organisms

Appendix C-VI-A........... Exceptions

Appendix C-VII............. The Purchase or Transfer of Transgenic Rodents

Appendix C-VIII............ Generation of BL1 Transgenic Rodents via Breeding

Appendix C-IX.............. Footnotes and References of Appendix C

APPENDIX D.................... MAJOR ACTIONS TAKEN UNDER THE NIH GUIDELINES

APPENDIX E.................... CERTIFIED HOST-VECTOR SYSTEMS (See Appendix I, Biological Containment)

Appendix E-I................ Bacillus subtilis

Appendix E-I-A............. Bacillus subtilis Host-Vector 1 Systems

Appendix E-I-B............. Bacillus subtilis Host-Vector 2 Systems

Appendix E-II............... Saccharomyces cerevisiae

Appendix E-II-A............ Saccharomyces cerevisiae Host-Vector 2 Systems

Appendix E-III............... Escherichia coli

Appendix E-III-A........... Escherichia coli (EK2) Plasmid Systems

Appendix E-III-B........... Escherichia coli (EK2) Bacteriophage Systems

Appendix E-IV.............. Neurospora crassa

Appendix E-IV-A........... Neurospora crassa Host-Vector 1 Systems

Appendix E-V............... Streptomyces

Appendix E-V-A........... Streptomyces Host-Vector 1 Systems

Appendix E-VI.............. Pseudomonas putida

Appendix E-VI-A........... Pseudomonas putida Host-Vector 1 Systems

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-II-A............ Biosafety Level 1 (BL1) (See Appendix G-III-M, Footnotes and References of Appendix G)

Appendix G-II-A-1......... Standard Microbiological Practices (BL1)

Appendix G-II-A-2......... Special Practices (BL1)

Appendix G-II-A-3......... Containment Equipment (BL1)

Appendix G-II-A-4......... Laboratory Facilities (BL1)

Appendix G-II-B............ Biosafety Level 2 (BL2) (See Appendix G-III-N, Footnotes and References of Appendix G)

Appendix G-II-B-1......... Standard Microbiological Practices (BL2)

Appendix G-II-B-2......... Special Practices (BL2)

Appendix G-II-B-3......... Containment Equipment (BL2)

Appendix G-II-B-4......... Laboratory Facilities (BL2)

Appendix G-II-C............ Biosafety Level 3 (BL3) (See Appendix G-III-P, Footnotes and References of Appendix G)

Appendix G-II-C-1......... Standard Microbiological Practices (BL3)

Appendix G-II-C-2......... Special Practices (BL3)

Appendix G-II-C-2-t....... Alternative Selection of Containment Equipment (BL3)

Appendix G-II-C-3......... Containment Equipment (BL3)

Appendix G-II-C-4......... Laboratory Facilities (BL3)

Appendix G-II-C-5......... Biosafety Level 3 Enhanced for Research Involving Risk Group 3 Influenza Viruses.  (See Appendices G-II-C-2-n, G-II-C-2-r, and G-II-C-4-i for additional guidance for facilities, waste handling, andserum collection for research involving mammalian­transmissible HPAI H5N1 virus.

Appendix G-II-C-5-a...... Containment, Practices, and Training for Research with Risk Group 3 Influenza Viruses (BL3 Enhanced).

Appendix G-II-C-5-b...... Containment for Animal Research.

Appendix G-II-C-5-c...... Occupational Health

Appendix G-II-D............ Biosafety Level 4 (BL4)

Appendix G-II-D-1......... Standard Microbiological Practices (BL4)

Appendix G-II-D-2......... Special Practices (BL4)

Appendix G-II-D-2-m.      Alternative Selection of Containment Equipment (BL4)

Appendix G-II-D-3......... Containment Equipment (BL4)

Appendix G-II-D-4......... Laboratory Facilities (BL4)

Appendix G-III.............. Footnotes and References of Appendix G

APPENDIX H.................... SHIPMENT

Appendix H-III............... Footnotes and References of Appendix H

APPENDIX I..................... BIOLOGICAL CONTAINMENT (See Appendix E, Certified Host-Vector Systems)

Appendix I-I.................. Levels of Biological Containment

Appendix I-I-A.............. Host-Vector 1 Systems

Appendix I-I-A-1............ Escherichia coli K-12 Host-Vector 1 Systems (EK1)

Appendix I-I-A-2............ Other Host-Vector 1 Systems

Appendix I-I-B.............. Host-Vector 2 Systems (EK2)

Appendix I-II................. Certification of Host-Vector Systems

Appendix I-II-A.............. Responsibility

Appendix I-II-B.............. Data to be Submitted for Certification

Appendix I-II-B-1........... Host-Vector 1 Systems Other than Escherichia coli K-12

Appendix I-II-B-2........... Host-Vector 2 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 OR SYNTHETIC NUCLEIC ACID MOLECULES

Appendix K-I................ Selection of Physical Containment Levels

Appendix K-II............... Good Large Scale Practice (GLSP)

Appendix K-III............... Biosafety Level 1 (BL1) - 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.................... GENE THERAPY POLICY CONFERENCES (GTPCS)

APPENDIX M.................... POINTS TO CONSIDER IN THE DESIGN AND SUBMISSION OF PROTOCOLS FOR THE TRANSFER OF recombinant or synthetic NUCLEIC ACID MOLECULES INTO ONE OR MORE HUMAN RESEARCH PARTICIPANTS (POINTS TO CONSIDER)

Appendix M-I................ Requirements for Protocol Submission, Review, and Reporting – Human Gene Transfer Experiments

Appendix M-I-A............ Requirements for Protocol Submission

Appendix M-I-B............ RAC Review Requirements

Appendix M-I-B-1.......... Initial RAC Review

Appendix M-I-B-2.......... Public RAC Review and Discussion

Appendix M-I-C............ Reporting Requirements

Appendix M-I-C-1.......... Initiation of the Clinical Investigation

Appendix M-I-C-2.......... Additional Clinical Trial Sites

Appendix M-I-C-3.......... Annual Reports

Appendix M-I-C-4.......... Safety Reporting

Appendix M-I-C-4-a....... Safety Reporting: Content and Format

Appendix M-I-C-4-b....... Safety Reporting: Time frames for Expedited Reports

Appendix M-I-C-5.......... Confidentiality

Appendix M-I-D............ Safety Assessment in Human Gene Transfer Research

Appendix M-II............... Description of the Proposal

Appendix M-II-A............ Objectives and Rationale of the Proposed Research

Appendix M-II-A-1......... Use of Recombinant or Synthetic Nucleic Acid Molecules for Therapeutic Purposes

Appendix M-II-A-2......... Transfer of Recombinant or Synthetic Nucleic Acid Molecules for Other Purposes

Appendix M-II-B............ Research Design, Anticipated Risks and Benefits

Appendix M-II-B-1......... Structure and Characteristics of the Biological System

Appendix M-II-B-2......... Preclinical Studies, Including Risk-Assessment Studies

Appendix M-II-B-2-a...... Delivery System

Appendix M-II-B-2-b...... Gene Transfer and Expression

Appendix M-II-B-2-c...... Retrovirus Delivery Systems

Appendix M-II-B-2-d...... Non-Retrovirus Delivery/Expression Systems

Appendix M-II-B-3......... Clinical Procedures, Including Research Participant Monitoring

Appendix M-II-B-4......... Public Health Considerations

Appendix M-II-B-5......... Qualifications of Investigators and Adequacy of Laboratory and Clinical Facilities

Appendix M-II-C............ Selection of the Human Subjects

Appendix M-III.............. Informed Consent

Appendix M-III-A........... Communication About the Study to Potential Participants

Appendix M-III-B........... Informed Consent Document

Appendix M-III-B-1........ General Requirements of Human Subjects Research

Appendix M-III-B-1-a.       Description/Purpose of the Study

Appendix M-III-B-1-b.      Alternatives

Appendix M-III-B-1-c.       Voluntary Participation

Appendix M-III-B-1-d.      Benefits

Appendix M-III-B-1-e.       Possible Risks, Discomforts, and Side Effects

Appendix M-III-B-1-f...... Costs

Appendix M-III-B-2........ Specific Requirements of Gene Transfer Research

Appendix M-III-B-2-a.       Reproductive Considerations

Appendix M-III-B-2-b.      Long-Term Follow-Up

Appendix M-III-B-2-c.       Request for Autopsy

Appendix M-III-B-2-d.      Interest of the Media and Others in the Research

Appendix M-IV............. Privacy

Appendix M-V.............. Special Issues

Appendix M-VI............. Footnotes of Appendix M

APPENDIX P.................... PHYSICAL AND BIOLOGICAL CONTAINMENT FOR RECOMBINANT OR SYNTHETIC NUCLEIC ACID MOLECULE RESEARCH INVOLVING PLANTS

Appendix P-I. .............. General Plant Biosafety Levels

Appendix P-II............... Physical Containment Levels

Appendix P-II-A............ Biosafety Level 1 - Plants (BL1-P)

Appendix P-II-A-1......... Standard Practices (BL1-P)

Appendix P-II-A-1-a....... Greenhouse Access (BL1-P)

Appendix P-II-A-1-b...... Records (BL1-P)

Appendix P-II-A-1-c....... Decontamination and Inactivation (BL1-P)

Appendix P-II-A-1-d...... Control of Undesired Species and Motile Macroorganisms (BL1-P)

Appendix P-II-A-1-e....... Concurrent Experiments Conducted in the Greenhouse (BL1-P)

Appendix P-II-A-2......... Facilities (BL1-P)

Appendix P-II-A-2-a....... Definitions (BL1-P)

Appendix P-II-A-2-b...... Greenhouse Design (BL1-P)

Appendix P-II-B............ Biosafety Level 2 - Plants (BL2-P)

Appendix P-II-B-1......... Standard Practices (BL2-P)

Appendix P-II-B-1-a....... Greenhouse Access (BL2-P)

Appendix P-II-B-1-b...... Records (BL2-P)

Appendix P-II-B-1-c....... Decontamination and Inactivation (BL2-P)

Appendix P-II-B-1-d...... Control of Undesired Species and Motile Macroorganisms (BL2-P)

Appendix P-II-B-1-e....... Concurrent Experiments Conducted in the Greenhouse (BL2-P)

Appendix P-II-B-1-f....... Signs (BL2-P)

Appendix P-II-B-1-g...... Transfer of Materials (BL2-P)

Appendix P-II-B-1-h....... Greenhouse Practices Manual (BL2-P)

Appendix P-II-B-2......... Facilities (BL2-P)

Appendix P-II-B-2-a....... Definitions (BL2-P)

Appendix P-II-B-2-b...... Greenhouse Design (BL2-P)

Appendix P-II-B-2-c....... Autoclaves (BL2-P)

Appendix P-II-B-2-d...... Supply and Exhaust Air Ventilation Systems (BL2-P)

Appendix P-II-B-2-e....... Other (BL2-P)

Appendix P-II-C............ Biosafety Level 3 - Plants (BL3-P)

Appendix P-II-C-1......... Standard Practices (BL3-P)

Appendix P-II-C-1-a....... Greenhouse Access (BL3-P)

Appendix P-II-C-1-b...... Records (BL3-P)

Appendix P-II-C-1-c....... Decontamination and Inactivation (BL3-P)

Appendix P-II-C-1-d...... Control of Undesired Species and Motile Macroorganisms (BL3-P)

Appendix P-II-C-1-e....... Concurrent Experiments Conducted in the Greenhouse (BL3-P)

Appendix P-II-C-1-f....... Signs (BL3-P)

Appendix P-II-C-1-g...... Transfer of Materials (BL3-P)

Appendix P-II-C-1-h....... Greenhouse Practices Manual (BL3-P)

Appendix P-II-C-1-i........ Protective Clothing (BL3-P)

Appendix P-II-C-1-j........ Other (BL3-P)

Appendix P-II-C-2......... Facilities (BL3-P)

Appendix P-II-C-2-a....... Definitions (BL3-P)

Appendix P-II-C-2-b...... Greenhouse Design (BL3-P)

Appendix P-II-C-2-c....... Autoclaves (BL3-P)

Appendix P-II-C-2-d...... Supply and Exhaust Air Ventilation Systems (BL3-P)

Appendix P-II-C-2-e....... Other (BL3-P)

Appendix P-II-D............ Biosafety Level 4 - Plants (BL4-P)

Appendix P-II-D-1......... Standard Practices (BL4-P)

Appendix P-II-D-1-a...... Greenhouse Access (BL4-P)

Appendix P-II-D-1-b...... Records (BL4-P)

Appendix P-II-D-1-c...... Decontamination and Inactivation (BL4-P)

Appendix P-II-D-1-d...... Control of Undesired Species and Motile Macroorganisms (BL4-P)

Appendix P-II-D-1-e...... Concurrent Experiments Conducted in the Greenhouse (BL4-P)

Appendix P-II-D-1-f....... Signs (BL4-P)

Appendix P-II-D-1-g...... Transfer of Materials (BL4-P)

Appendix P-II-D-1-h...... Greenhouse Practices Manual (BL4-P)

Appendix P-II-D-1-i....... Protective Clothing (BL4-P)

Appendix P-II-D-2......... Facilities (BL4-P)

Appendix P-II-D-2-a...... Greenhouse Design (BL4-P)

Appendix P-II-D-2-b...... Autoclaves (BL4-P)

Appendix P-II-D-2-c...... Supply and Exhaust Air Ventilation Systems (BL4-P)

Appendix P-II-D-2-d...... Other (BL4-P)

Appendix P-III............... Biological Containment Practices

Appendix P-III-A........... Biological Containment Practices (Plants)

Appendix P-III-B........... Biological Containment Practices (Microorganisms)

Appendix P-III-C........... Biological Containment Practices (Macroorganisms)

APPENDIX Q.................... PHYSICAL AND BIOLOGICAL CONTAINMENT FOR RECOMBINANT OR SYNTHETIC NUCLEIC ACID MOLECULE RESEARCH INVOLVING ANIMALS

Appendix Q-I................ General Considerations

Appendix Q-I-A............. Containment Levels

Appendix Q-I-B............. Disposal of Animals (BL1-N through BL4-N)

Appendix Q-II............... Physical and Biological Containment Levels

Appendix Q-II-A............ Biosafety Level 1 - Animals (BL1-N)

Appendix Q-II-A-1......... Standard Practices (BL1-N)

Appendix Q-II-A-1-a...... Animal Facility Access (BL1-N)

Appendix Q-II-A-1-b...... Other (BL1-N)

Appendix Q-II-A-2......... Animal Facilities (BL1-N)

Appendix Q-II-B............ Biosafety Level 2 - Animals (BL2-N) (See Appendix Q-III-A, Footnotes and References for Appendix Q)

Appendix Q-II-B-1......... Standard Practices (BL2-N)

Appendix Q-II-B-1-a...... Animal Facility Access (BL2-N)

Appendix Q-II-B-1-b...... Decontamination and Inactivation (BL2-N)

Appendix Q-II-B-1-c...... Signs (BL2-N)

Appendix Q-II-B-1-d...... Protective Clothing (BL2-N)

Appendix Q-II-B-1-e...... Records (BL2-N)

Appendix Q-II-B-1-f....... Transfer of Materials (BL2-N)

Appendix Q-II-B-1-g...... Other (BL2-N)

Appendix Q-II-B-2......... Animal Facilities (BL2-N)

Appendix Q-II-C............ Biosafety Level 3 - Animals (BL3-N) (See Appendix Q-III-B, Footnotes and References for Appendix Q)

Appendix Q-II-C-1......... Standard Practices (BL3-N)

Appendix Q-II-C-1-a...... Animal Facility Access (BL3-N)

Appendix Q-II-C-1-b...... Decontamination and Inactivation (BL3-N)

Appendix Q-II-C-1-c...... Signs (BL3-N)

Appendix Q-II-C-1-d...... Protective Clothing (BL3-N)

Appendix Q-II-C-1-e...... Records (BL3-N)

Appendix Q-II-C-1-f....... Transfer of Materials (BL3-N)

Appendix Q-II-C-1-g...... Other (BL3-N)

Appendix Q-II-C-2......... Animal Facilities (BL3-N)

Appendix Q-II-D............ Biosafety Level 4 - Animals (BL4-N) (See Appendix Q-III-C, Footnotes and References for Appendix Q)

Appendix Q-II-D-1......... Standard Practices (BL4-N)

Appendix Q-II-D-1-a...... Animal Facility Access (BL4-N)

Appendix Q-II-D-1-b...... Decontamination and Inactivation (BL4-N)

Appendix Q-II-D-1-c...... Signs (BL4-N)

Appendix Q-II-D-1-d...... Protective Clothing (BL4-N)

Appendix Q-II-D-1-e...... Records (BL4-N)

Appendix Q-II-D-1-f....... Transfer of Materials (BL4-N)

Appendix Q-II-D-1-g...... Other (BL4-N)

Appendix Q-II-D-2......... Animal Facilities (BL4-N)

Appendix Q-III.............. Footnotes and References for Appendix Q

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LIST OF TABLES

Appendix B - Table 1.         Basis for the Classification of Biohazardous Agents by Risk Group

Appendix G - Table 1.        Possible Alternate Combinations Of Physical And Biological Containment Safeguards

Appendix K - Table 1.        Comparison of Good Large Scale Practice (GLSP) and Biosafety Level (BL) - Large Scale (LS) Practice