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  1. THE  NIHRECOMBINANTDNA 2002 GUIDELINES  East Carolina University September 5, 2007

  2. INTRODUCTION The National Institutes of Health (NIH) Guidelines for Research Involving  RecombinantDNA Molecules is the reference document for research compliance with recombinantDNA molecules.


  4. REGULATORY OVERVIEW  • If your institution receives Federal funding, then it must comply with the NIH Guidelines for recombinantDNA research. • Even if a project is privately sponsored, that research experiment must still be conducted in accordance with the NIH Guidelines.

  5. DEFINITIONS  • Defined as either: 1.  Molecules constructed outside living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell; or 2.  DNA molecules that result from the replication of those described above. 

  6. SOMETHING TO REMEMBER  Non-compliance to the NIH Guidelines may result in: • forfeiture of funding • suspensions or other limitations • a requirement for NIH review and approval for all recombinantDNA research


  8. RISK GROUPS CLASSIFICATION OF ORGANISMS  Risk Group  1: not known to cause disease 2: rarely serious disease, with therapeutic intervention 3: serious, lethal disease with therapeutic intervention 4: serious, lethal disease with no therapeutic intervention

  9. RISK ASSESSMENT  • Review classification of organism • Review research procedures to be performed • Assess available facility/physical barriers (biosafety levels) • Potential for inadvertent release • Other factors, such as volume, concentration, replication competency

  10. CONTAINMENT  • Standard practices • Special procedures, equipment • Available facility/facility design • Biological barriers


  12. Abbreviations • IBC = ECU Institutional Biological Safety Committee • RAC = U.S. Recombinant DNA Advisory Committee • IRB = ECU Institutional Review Board (Human Subjects) • OBA = NIH Office of Biotechnology Assessment

  13. SECTION III-A Major Actions  Requires: IBC, RAC, NIH Director Review and Approval prior to the initiation of work • Drug resistance to organisms • Prevent compromise to agriculture/medicine

  14. SECTION III-B  Requires: NIH/OBA, IBC Review and Approval Before Initiation of Work • Containment determined by NIH/OBA • Example: Deliberate Cloning of Toxin Molecules Lethal to Vertebrates at an LD50 of Less Than 100 Nanograms/Kg of Body Weight (e.g., Botulinum Toxin)

  15. SECTION III-C  Deliberate Transfer of RecombinantDNA into Research Participants  Requires: RAC Review, IBC, and IRB Review and Approval Before Participant Enrollment • Requires RAC Review prior to local institutional review. • Must be reviewed by NIH prior to research participant enrollment.

  16. SECTION III-D  Requires IBC Review Prior to the Initiation of Work  Requires: IBC Review and Approval prior to the initiation of work • Involves RG 2-4 agents, host/vector system • Cloned DNA from RG 2-4 agents into non-pathogenic prokaryotes • RG 2-4 agents into whole animals, usually transgenic • Recombinant plants

  17. SECTION III-E  IBC notification at the initiation of work  Requires: IBC notification at the initiation of work (BL-1 containment) • DNA Contains Less than 2/3 viral genome • Transgenic Rodents with ABSL1 containment • Whole Plants-minimal containment required

  18. SECTION III-F Exempt  Exempt from the NIH Guidelines and Does Not Require IBC Review and Approval RecombinantDNA that is: • Not in Organisms • Not a risk to the environment

  19. ECU Researchers are advised to consult with Biological Safety to verify the NIH classification of their planned work.


  21. RESPONSIBILITIES  EAST CAROLINA UNIVERSITY • Ensure compliance with NIH Guidelines • Establish IBC • Appoint a Biosafety Officer • Ensure IBC has expertise in the research that is reviewed • Establish a medical surveillance program as needed • Report all accidents to the NIH

  22. IBC MEMBER THE BIOSAFETY OFFICER When the institution conducts recombinantDNA research at BL3, BL4, or Large Scale (greater than 10 Liters), a Biological Safety Officer is mandatory and shall be a member of the Institutional Biosafety Committee (see section lV-B-3, Biological Safety Officer).

  23. RESPONSIBILITIES IBC(SECTION IV-B-2)  The Institutional Biosafety Committee must be composed of no fewer than five members so selected that they collectively have experience and expertise in recombinantDNA technology and the capability to assess the safety of recombinantDNA research and to identify any potential risk to public health or the environment. (IV-B-2-a-(1)


  25. RESPONSIBILITIES IBC-IRB JOINT REVIEW Sponsored Phase 1 clinical trials  If the East Carolina University is part of a non-NIH funded Phase 1 Clinical Trial protocol and receives NIH funding for other research, it is obligated to review the non-NIH sponsored research and follow the NIH Guidelines or possibly lose NIH funding for all research.

  26. RESPONSIBILITIES IBC-IRB INTERACTION  • The East Carolina University Institutional Review Board (IRB) must become familiar with the provisions of Section III-C-1, the introduction of recombinantDNA molecules to research participants. • The IRB and IBC must jointly review gene therapy applications.

  27. IBC GENE THERAPY EVALUATION  The IBC shall evaluate: • adverse events in previous clinical trials and animal studies to predict the potential of similar events in future trials • the appropriate level of monitoring for potential microbial shedding

  28. IRB GENE THERAPY EVALUATION  It is the responsibility of the IRB to determine: • the risks to subjects (research participants) • the anticipated benefits to subjects • the importance of the knowledge that may reasonably be expected to result • the informed consent process to be employed

  29. IBC-IACUC INTERACTIONS  Certain Institutional Animal Care and Use Committee (IACUC) reviewed experiments require IBC review and approval: • Section III-D-4, whole animals • Section III-E-3, transgenic rodents • Appendix Q: Containment requirements for large mammals • Any introduction of biohazardous agents (shedding)

  30. IBC-IACUC INTERACTIONS  • Both the IACUC and IBC must review of any of the aforementioned experiments. • While the IACUC traditionally examines pain and suffering, euthanasia and vivaria housing, the IBC shall recommend good work practices with recombinantDNA as described in Animal Biosafety Levels 1-3.

  31. IBC-IACUC INTERACTIONS  The IBC and IACUC should also ensure: • biohazard vivaria areas are kept clean • animal carcasses are properly disposed of • infected animals are housed separately • infected animals are transported safely • infected animals do not infect humans

  32. REPORTING ACCIDENTS AND INCIDENTS  • All laboratory accidents or incidents involving recombinantDNA molecules must be reported to NIH, OBA and the IBC. • All adverse events in gene transfer experiments must be reported to NIH, OBA, the IBC and the IRB, even if thought not to be in conjunction with the gene transfer intervention.

  33. RAC APPROVAL  The Institutional Biosafety Committee may not authorize initiation of experiments which are not explicitly covered by the NIH Guidelines until NIH (with the advice of the RAC when required) establishes the containment requirement. lV-B-2-b-(8)

  34. IBC ADMINISTRATIVE  REQUIREMENTS  East Carolina University shall file an annual report with NIH/OBA which includes: (i) a roster of all IBC members clearly indicating the Chair, contact person, Biological Safety Officer (if applicable), and identify the specific expertise of the committee members, e.g., animal expert, human gene therapy expert. (ii) biographical sketches of all IBC members (including community members).

  35. IBC ADMINISTRATIVE  REQUIREMENTS  Upon request, East Carolina University shall make available to the public all IBC meeting minutes and any documents submitted to or received from funding agencies.

  36. However East Carolina University may redact proprietary or private information for all requested documents, such as trade secrets, confidential commercial information or home addresses and phone numbers of IBC members. NIH Guidelines do not preclude East Carolina University from complying with any applicable state laws or institutional policy regarding public requests; e.g., redaction of certain information under North Carolina law is permissible.

  37. IBC ADMINSITRATIVE  REQUIREMENTS  If public comments are made on IBC actions, the institution shall forward both the public comments and the IBC’s response to the Office of Biotechnology Activities, National Institutes of Health/MSC 7010, 6000 Executive Boulevard, Suite 302, Bethesda, Maryland 20892-7010, (301) 496-9838.  

  38. CONCLUSION This presentation was designed to inform the audience on the key provisions of the  NIH 2002 Guidelines.  The IBC must interact as necessary with other institutional committees and ensure that research involving recombinantDNA molecules is adequately reviewed.