Recombinant or Synthetic DNA/RNA in Human Research Participants

Institutional Biosafety Committee Review

Human gene transfer and all other research involving recombinant or synthetic nucleic acids in human research participants that is sponsored by or conducted at the University of Washington (UW)requires review and approval by the UW Institutional Biosafety Committee (IBC). Studies involving deliberate transfer of genes into human research participants (human gene transfer) via either of the following are covered by the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) Section III-C and require review by the NIH Office of Biotechnology Activities (OBA) Recombinant DNA Advisory Committee (RAC) and the UW IBC:

  1. Recombinant nucleic acid molecules, or DNA or RNA derived from recombinant nucleic acid molecules; or
  2. Synthetic nucleic acid molecules or DNA, or RNA derived from synthetic nucleic acid molecules, that meet any one of the following criteria:
    • Contain more than 100 nucleotides; or
    • Possess biological properties that enable integration into the genome (e.g., cis elements involved in integration); or
    • Have the potential to replicate in a cell; or
    • Can be translated or transcribed.
(Note that the above newly amended definition of human gene transfer is as stipulated by the March 2013 amendment to the NIH Guidelines.) Regardless of exemption from NIH Guidelines Section III-C, all clinical research involving recombinant or synthetic nucleic acids must be reviewed by the UW IBC. The IBC review process begins once all documents of the Principal Investigator's application packet are submitted. Please be aware that IBC review cannot be completed without recommendations from the RAC. The Principal Investigator should allow eight weeks for completion of the review process due to the large amount of material for review by the IBC subcommittee.

The UW IBC reviews the clinical proposal and RAC recommendations; review focuses on public protection (i.e., research personnel, care givers, general public, etc.). The RAC makes recommendations on research involving the use of recombinant DNA and on developments in recombinant DNA technology, including human gene transfer trials. Recommendations from the RAC are required to be reviewed by the UW IBC.

Institutional Review Board (IRB) approval is required prior to subject enrollment. Other regulatory authorizations may apply. No research participant may be enrolled until:

  1. The RAC review process has been completed;
  2. Institutional Biosafety Committee (IBC) approval from the clinical trial site has been obtained;
  3. Institutional Review Board (IRB) approval has been obtained; and
  4. All applicable regulatory authorization(s) have been obtained.
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IBC Application Packet

All of the following applicable documents must be submitted to initiate IBC review:

  • Biological Use Authorization (BUA) Application
  • Completed Appendix M from the NIH Guidelines
  • Any correspondence with the NIH OBA RAC (e.g., OBA RAC response letter, OBA RAC reviewers' comments, PI response to OBA RAC reviewers)
  • Clinical protocol
  • Investigator's brochure
  • PI's curriculum vitae (CV)
  • Proposed consent forms
*Please allow eight weeks for completion of IBC review after all documents are submitted.*

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NIH OBA Reporting Requirements

The following summarizes the NIH OBA reporting requirements for Principal Investigators. Copies of NIH OBA submissions, including cover letters, are sent to the University of Washington (UW) IBC Coordinator at ehsbio@uw.edu or Box 357165.

NIH Reporting Requirement
When
What to Submit
Initiation of clinical investigationNo later than 20 working days after enrollment of first research participant
See Appendix M-I-C-1
Additional clinical trial sitesPrior to enrollment of research participants at the new clinical trial site
See Appendix M-I-C-2
Annual reportsWithin 60 days after the one-year anniversary of the date on which the investigational new drug (IND) application went into effect, and after each subsequent anniversary until the trial is completed
See Appendix M-I-C-3
Safety Reporting*
When
See Appendix M-I-C-4
Serious adverse event: fatal or life-threatening, unexpected, and associated with use of gene transfer product.Must be reported as soon as possible, but not later than 7 calendar days after sponsor's initial receipt of the information
See Appendix M-I-C-4-a
Serious adverse event: unexpected and associated with the use of the gene transfer product, but not fatal or life-threateningMust be reported as soon as possible, but not later than 15 calendar days after the sponsor's initial receipt of the information
See Appendix M-I-C-4-a
If, after further evaluation, an adverse event initially considered not to be associated with the use of the gene transfer product is subsequently determined to be associatedMust be reported within 15 days of the determination
See Appendix M-I-C-4-a
If relevant additional clinical and laboratory data becomes available following an initial serious adverse event reportMust be reported within 15 calendar days of the sponsor's receipt of the information
See Appendix M-I-C-4-a
If a serious adverse event occurs after the end of a clinical trial and is determined to be associated with the use of the gene transfer productMust be reported within 15 calendar days of the determination
See Appendix M-I-C-4-a
Any finding from tests in laboratory animals that suggests a significant risk for human research participants including reports of mutagenicity, teratogenicity, or carcinogenicityMust be reported as soon as possible, but not later than 15 calendar days after the sponsor's initial receipt of the information
See Appendix M-I-C-4-a

*Adverse events can be reported using the NIH/FDA Genetic Modification Clinical Research Information System (GeMCRIS).

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Resources

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Questions


Contact the UW Institutional Biosafety Committee (IBC) Coordinator:
206.221.7770
ehsbio@uw.edu.
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