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Human Subjects Studies that Require IBC Approval

Introduction of recombinant DNA (plasmids) or gene transfer vectors (including viral vectors) into human subjects

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NIH Regulations

Per UR Regulations, investigators must submit their protocols to the IBC for preliminary review, before the submission can go to the RAC. The purpose of this preliminary review is to identify any potential review issues/concerns so as to facilitate the review and approval process, both at the RAC and the IBC. Following initial IBC screening, protocols must then be sent to the RAC for approval. NIH Guidelines require such approval BEFORE final IBC approval may be issued.

All Experiments Involving the Deliberate Transfer of Recombinant DNA or DNA or RNA Derived from Recombinant DNA into One or More Human Research Participants (including recombinant deoxyribonucleic acid (DNA) molecules, and/or organisms and viruses containing recombinant DNA molecules) are subject to review and oversight by the Institutional Biosafety Committee and the Institutional Research Subjects Review Board, as well as by NIH/OBA and the RAC, as outlined in the NIH Guidelines on Recombinant DNA Molecules. Final IBC approval of human gene transfer studies will not be granted until RAC review has been completed, and the IBC is mandated to consider RAC review comments in its decision-making process.

Section IV-B-1-f of the NIH Guidelines states that, when the institution participates in or sponsors recombinant DNA research involving human subjects, the following must occur:

    1. the Institutional Biosafety Committee has adequate expertise and training (using ad hoc consultants as deemed necessary), and
    2. all aspects of Appendix M, Points to Consider in the Design and Submission of Protocols for the Transfer of Recombinant DNA Molecules into One or More Human Subjects (Points to Consider), have been appropriately addressed by the Principal Investigator prior to submission to NIH/OBA, and
    3. RAC review must occur prior to IBC approval, and
    4. RAC, IBC, and RSRB approval must occur prior to enrollment of any human research participants, and
    5. The Investigator must comply with all surveillance, data reporting, and adverse event requirements set forth in the NIH Guidelines.

IBC Authority and Oversight

As required by the NIH Guidelines, the University of Rochester Institutional Biosafety Committee (UR IBC) oversees and regulates all research with biohazardous agents and recombinant DNA molecules at the University of Rochester. Recombinant DNA molecules are defined below.

The University of Rochester has also determined that, in addition to performing these required oversight functions, the IBC will also exercise oversight of technologies that directly manipulate gene expression in cells using small informational molecules (small polymers based on DNA, RNA or mimetics thereof).

Definitions:

Recombinant DNA:  The NIH guidelines define recombinant DNA molecules as either: (i) molecules that are constructed outside living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell, or (ii) molecules that result from the replication of those described in (i) above.

Synthetic DNA segments which are likely to yield a potentially harmful polynucleotide or polypeptide (e.g., a toxin or a pharmacologically active agent) are considered as equivalent to their natural DNA counterpart. If the synthetic DNA segment is not expressed in vivo as a biologically active polynucleotide or polypeptide product, it is exempt from the NIH Guidelines.

Informationally-based technologies that directly manipulate gene expression in cells:  Technologies intended to produce disruption or modification of gene transcription, RNA processing or gene product formation, and that rely upon the introduction into cells of informational molecules to achieve this (small polymers based on DNA, RNA or mimetics of DNA or RNA) will fall within the purview of the UR IBC. Non-limiting examples of these technologies include RNAi, dsRNA, antisense oligonucleotide (PNAs, LNAs. etc). The IBC will provide guidance to investigators and through its review address safety concerns pursuant to use of these technologies, including (but not limited to) safety of laboratory workers, and other members of University community. The IBC will also advise the Research Subject Review Board on an as-needed basis on scientific issues that may be related to the safety of human subjects who participate in clinical studies that use such modalities.

Institutional Review and Approval Process

Overview of RAC Registration and Review: Prior to the initiation of any experiment that involves the use of Recombinant DNA Molecules in Human Research Participants, the Principal Investigator must submit the proposed experimental plan, a completed Appendix M, consent forms and other required documentation to the IBC for preliminary review before the submission can go to the RAC for registration and review. Investigators should consult the RAC Review: Paperwork Submission List used by the IBC, in order to determine the documents that should be submitted to the IBC.

Overview of RSRB Registration and Review: Prior to the initiation of any experiment that involves the use of Recombinant DNA Molecules, the Principal Investigator must submit the proposed experimental plan, and its associated Consent forms, to the RSRB for registration and approval.

Overview of IBC Registration and Review: Prior to the initiation of any human clinical trial that involves the use of Recombinant DNA Molecules, the Principal Investigator must submit the proposed experimental plan to the IBC for review. This will be done after the investigator has been notified by the RAC of its findings.

The RSRB can review the submission in parallel with the IBC review, with the understanding that the IBC review and approval may affect changes to the protocol and/or consent form submitted to the RSRB. Note that adequate turn-around time for project evaluation and review must be allowed.

In preparing an adequate description of the proposed research for review by the IBC, the PI should address the specific points in Appendix M of the NIH Guidelines. This should be done in a detailed manner. Note that Appendix M of the Guidelines states that:

In its evaluation of human gene transfer proposals, RAC will consider whether the design of such experiments offers adequate assurance that their consequences will not go beyond their purpose, which is the same as the traditional purpose of clinical investigation, namely, to protect the health and well being of human subjects being treated while at the same time gathering generalizable knowledge. Two possible undesirable consequences of the transfer of recombinant DNA would be unintentional: (i) vertical transmission of genetic changes from an individual to his/her offspring, or (ii) horizontal transmission of viral infection to other persons with whom the individual comes in contact.

The IBC will review all protocols with this same purpose, regardless of whether they are NIH-sponsored or not.

Materials to be Provided to the IBC for Gene Transfer Studies Involving Human Research Participants

After the investigator has been notified by the RAC of its findings, the IBC requires submission of the following forms:

    1. Human Subjects Study Registration Form (Form HS)
    2. Mammalian Virus Vector Registration Form (if appropriate)

In addition, the following supporting documents must also be provided for IBC review. Note that one copy of all the required documents must be sent to the IBC Program Coordinator, RC Box 278878, who will ensure the completeness of the materials provided.

Once documents are determined to be complete, the IBC will request all additional copies as needed for appropriate review.

    1. Copy of RAC review comments, and proof of RAC review
    2. Scientific abstract of the study
    3. Non-technical (lay) abstract of the study
    4. Responses to Appendix M-II through M-V (Description of the Proposal, Informed Consent, Privacy, and Special Issues). Responses to Appendix M should be provided in the form of either written answers or references to specific sections of the protocol or its appendices. If the latter, please cite specific page numbers from the protocol or appendices. Please note that Appendix M should be read by the principal investigator in its entirety as it contains essential information on the conduct of and reporting requirements for human gene transfer clinical trials.
    5. Clinical protocol
    6. Informed consent document (see Appendix M-III and contact the RSRB for guidance)
    7. Appendices (including tables, figures, and manuscripts)
    8. Curricula vitae for the PI and for each key professional person (no more than two pages in biographical sketch format); and
    9. Names of all personnel who will administer recombinant DNA to subjects, and who will collect and analyze samples from study subjects. This list should include dates of any laboratory-specific training performed, & of the most recent OSHA training (Bloodborne Pathogens) if this information is available.
    10. Publicly available Adverse Event reports relating to the DNA molecule
    11. Expected Adverse Events, based on pre-clinical information related to the DNA molecule
    12. Investigator Brochure
    13. IBC laboratory registration, if applicable

This list of documents is taken from the NIH Guidelines for Research Involving Recombinant DNA Molecules, Appendix M. Please refer to Appendix M in its entirety for a complete description of the OBA/Recombinant DNA Advisory Committee (RAC) review and approval process.

Follow up activities by the IBC, upon receipt of complete documentation will include, protocol review/evaluation as well as (1) a survey of the facility where the drug is stored/dispensed/administered, and (2) a review of study personnel training relevant to OSHA compliance.

No later than 20 working days after enrollment of the first research participant, the Principal Investigator must submit the required documentation to the OBA, as outlined in Appendix M-1-C-1 (Initiation of Clinical Investigation).

Reporting Requirements (including Adverse Event Reporting)

All Investigators must comply with the Reporting Requirements of Appendix M of the NIH Guidelines. For more information, go to the following link:

New Guidelines for Reporting Adverse Events and Submitting Reports from Data and Safety Monitoring Boards to the IRB

 

Human Studies in Which Induction or Enhancement of an Immune Response to a Vector-Encoded Microbial Immunogen is the Major Goal

Human studies in which induction or enhancement of an immune response to a vector-encoded microbial immunogen is the major goal, such an immune response has been demonstrated in model systems, and the persistence of the vector-encoded immunogen is not expected, are exempt from the Requirements of Appendix M-I of the NIH Guidelines (see Footnotes of Appendix M) .

These studies, however, must still be reviewed by the IBC. Registration instructions can be found at the following link:

Introduction of Genetically Engineered Micro-organisms or Infectious Agents into Human Subjects

This page last updated 4/3/07. Disclaimer