NIH GUIDELINES FOR RESEARCH

INVOLVING

RECOMBINANT OR SYNTHETIC

Nucleic Acid MOLECULES

(NIH GUIDELINES)

 

April 2024

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

 

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Visit the NIH OSP Web site at:

https://osp.od.nih.gov

 

NIH Office of Science Policy Contact Information:

 

Office of Science Policy, National Institutes of Health, 6705 Rockledge Drive, Suite 630, MSC 7985, Bethesda, MD  20892-7985 (20817 for non-USPS mail), (301) 496-9838; (301) 496-9839 (fax).

 

For inquiries, information requests, and report submissions:                    NIHGuidelines@od.nih.gov

 

 

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)

Amendment Effective April 27, 2016, Federal Register, March 22, 2016 (81 FR 15315)

Amendment Effective April 15, 2016, Federal Register, April 15, 2016 (81 FR 22286)

Amendment Effective April 25, 2019, Federal Register, April 26, 2019 (84 FR 17858)

Amendment Effective September 30, 2024, Federal Register, April 5, 2024 (89 FR 24016)


 

TABLE OF CONTENTS

 

NIH Office of Science Policy Contact Information: 1

SECTION I....................... SCOPE OF THE NIH GUIDELINES. 10

Section I-A................... Purpose. 10

Section I-B................... Definition of Recombinant and Synthetic Nucleic Acid Molecules. 10

Section I-C................... General Applicability. 10

Section I-D................... Compliance with the NIH Guidelines. 11

Section I-E................... General Definitions. 11

 

SECTION II...................... SAFETY CONSIDERATIONS. 12

Section II-A.................. Risk Assessment 12

Section II-A-1............... Risk Groups. 12

Section II-A-2............... Criteria for Risk Groups. 12

Section II-A-3............... Comprehensive Risk Assessment 12

Section II-B.................. Containment 14

 

SECTION III..................... EXPERIMENTS COVERED BY THE NIH GUIDELINES. 16

Section III-A................. Experiments that Require NIH Director Approval and Institutional Biosafety Committee Approval Before Initiation (See Section IV-C-1-b-(1), Major Actions). 16

Section III-A-1.............. Major Actions under the NIH Guidelines. 16

Section III-B................. Experiments That Require NIH OSP and Institutional Biosafety Committee Approval Before Initiation. 17

Section III-B-1.............. Experiments Involving the Cloning of Toxin Molecules with LD50 of Less than 100 Nanograms per Kilogram Body Weight 17

Section III-B-2.............. Experiments that have been Approved (under Section III-A-1-a) as Major Actions under the NIH Guidelines. 17

Section III-C................. Experiments Involving Human Gene Transfer that Require Institutional Biosafety Committee Approval Prior to Initiation. 17

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. 17

Section III-D................. Experiments that Require Institutional Biosafety Committee Approval Before Initiation. 18

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) 18

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. 18

Section III-D-3.............. Experiments Involving the Use of Infectious DNA or RNA Viruses or Defective DNA or RNA Viruses in the Presence of a Helper System in Tissue Culture Systems. 19

Section III-D-4.............. Experiments Involving Whole Animals. 19

Section III-D-5.............. Experiments Involving Whole Plants. 20

Section III-D-6.............. Experiments Involving More than 10 Liters of Culture. 21

Section III-D-7.............. Experiments Involving Influenza Viruses. 21

Section III-D-8.............. Experiments Involving Gene Drive Modified Organisms. 21

Section III-E................. Experiments that Require Institutional Biosafety Committee Notice Simultaneous with Initiation. 22

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. 23

Section III-E-2.............. Experiments Involving Whole Plants. 23

Section III-E-3.............. Experiments Involving Transgenic Rodents. 24

Section III-F................. Exempt Experiments. 24

SECTION IV..................... ROLES AND RESPONSIBILITIES. 25

Section IV-A................. Policy. 25

Section IV-B................. Responsibilities of the Institution. 25

Section IV-B-1.............. General Information. 25

Section IV-B-2.............. Institutional Biosafety Committee (IBC) 27

Section IV-B-2-a........... Membership and Procedures. 27

Section IV-B-2-b........... Functions. 28

Section IV-B-3.............. Biological Safety Officer (BSO) 29

Section IV-B-4.............. Plant, Plant Pathogen, or Plant Pest Containment Expert 30

Section IV-B-5.............. Animal Containment Expert 30

Section IV-B-6.............. Human Gene Therapy Expertise. 30

Section IV-B-7.............. Principal Investigator (PI) 30

Section IV-B-7-a........... General Responsibilities. 30

Section IV-B-7-b........... Information to Be Submitted by the Principal Investigator to NIH OSP. 31

Section IV-B-7-c........... Submissions by the Principal Investigator to the Institutional Biosafety Committee. 31

Section IV-B-7-d........... Responsibilities of the Principal Investigator Prior to Initiating Research. 32

Section IV-B-7-e........... Responsibilities of the Principal Investigator During the Conduct of the Research. 32

Section IV-C................ Responsibilities of the National Institutes of Health (NIH) 32

Section IV-C-1............. NIH Director 32

Section IV-C-1-a.......... General Responsibilities. 32

Section IV-C-1-b.......... Specific Responsibilities. 33

Section IV-C-1-b-(1)..... Major Actions. 33

Section IV-C-1-b-(2)..... Minor Actions. 33

Section IV-C-2............. Office of Science Policy (OSP) 34

Section IV-C-3............. Other NIH Components. 34

Section IV-D................ Voluntary Compliance. 34

Section IV-D-1............. Basic Policy - Voluntary Compliance. 34

Section IV-D-2............. Institutional Biosafety Committee Approval - Voluntary Compliance. 35

Section IV-D-3............. Certification of Host-Vector Systems - Voluntary Compliance. 35

Section IV-D-4............. Requests for Exemptions and Approvals - Voluntary Compliance. 35

Section IV-D-5............. Protection of Proprietary Data - Voluntary Compliance. 35

Section IV-D-5-a.......... General 35

Section IV-D-5-b.......... Pre-submission Review. 36

 

SECTION V...................... FOOTNOTES AND REFERENCES OF SECTIONS I THROUGH IV. 36

 

APPENDIX A.................... EXEMPTIONS UNDER SECTION III-F-6--SUBLISTS OF NATURAL EXCHANGERS. 37

Appendix A-I................ Sublist A. 38

Appendix A-II............... Sublist B. 38

Appendix A-III.............. Sublist C. 38

Appendix A-IV.............. Sublist D. 38

Appendix A-V............... Sublist E. 39

Appendix A-VI.............. Sublist F. 39

 

APPENDIX B.................... CLASSIFICATION OF HUMAN ETIOLOGIC AGENTS ON THE BASIS OF HAZARD. 39

Appendix B-I................ Risk Group 1 (RG1) Agents. 39

Appendix B-II............... Risk Group 2 (RG2) Agents. 40

Appendix B-II-A............ Risk Group 2 (RG2) - Bacterial Agents Including Chlamydia. 40

Appendix B-II-B............ Risk Group 2 (RG2) - Fungal Agents. 41

Appendix B-II-C........... Risk Group 2 (RG2) - Parasitic Agents. 41

Appendix B-II-D........... Risk Group 2 (RG2) - Viruses. 42

Appendix B-III.............. Risk Group 3 (RG3) Agents. 43

Appendix B-III-A........... Risk Group 3 (RG3) - Bacterial Agents Including Rickettsia. 43

Appendix B-III-B........... Risk Group 3 (RG3) - Fungal Agents. 44

Appendix B-III-C.......... Risk Group 3 (RG3) - Parasitic Agents. 44

Appendix B-III-D.......... Risk Group 3 (RG3) - Viruses and Prions. 44

Appendix B-IV.............. Risk Group 4 (RG4) Agents. 45

Appendix B-IV-A.......... Risk Group 4 (RG4) - Bacterial Agents. 45

Appendix B-IV-B.......... Risk Group 4 (RG4) - Fungal Agents. 45

Appendix B-IV-C.......... Risk Group 4 (RG4) - Parasitic Agents. 45

Appendix B-IV-D.......... Risk Group 4 (RG4) - Viral Agents. 45

Appendix B-V............... Animal Viral Etiologic Agents in Common Use. 46

Appendix B-V-1............ Murine Retroviral Vectors. 46

 

APPENDIX C.................... EXEMPTIONS UNDER SECTION III-F-8. 46

Appendix C-I................ Recombinant or Synthetic Nucleic Acid Molecules in Tissue Culture. 47

Appendix C-I-A............ Exceptions. 47

Appendix C-II............... Escherichia coli K-12 Host-Vector Systems. 47

Appendix C-II-A........... Exceptions. 47

Appendix C-III.............. Saccharomyces Host-Vector Systems. 48

Appendix C-III-A.......... Exceptions. 48

Appendix C-IV.............. Kluyveromyces Host-Vector Systems. 48

Appendix C-IV-A.......... Exceptions. 48

Appendix C-V............... Bacillus subtilis or Bacillus licheniformis Host-Vector Systems. 48

Appendix C-V-A........... Exceptions. 48

Appendix C-VI.............. Extrachromosomal Elements of Gram Positive Organisms. 49

Appendix C-VI-A.......... Exceptions. 50

Appendix C-VII............. The Purchase or Transfer of Transgenic Rodents. 50

Appendix C-VIII............ Generation of BL1 Transgenic Rodents via Breeding. 50

Appendix C-IX.............. Footnotes and References of Appendix C. 50

 

APPENDIX D.................... MAJOR ACTIONS TAKEN UNDER THE NIH GUIDELINES. 51

 

APPENDIX E.................... CERTIFIED HOST-VECTOR SYSTEMS (See Appendix I, Biological Containment) 72

Appendix E-I................ Bacillus subtilis. 72

Appendix E-I-A............. Bacillus subtilis Host-Vector 1 Systems. 72

Appendix E-I-B............. Bacillus subtilis Host-Vector 2 Systems. 72

Appendix E-II.