LBH IRB Guide #14: Human Gene Transfer/Recombinant DNA Research Page 1 of 4

DEPARTMENTOFRESEARCH

Version 2, 07-02-10

Institutional Review Board

Human Gene Transfer/Recombinant DNA Research

Guidelines

Overview

Human Gene Transfer Research is defined by federal regulations as “any deliberate transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA (technology), into human research participants.” Special provisions are necessary for conducting human gene transfer research at LBH. Principal investigators (PIs) must complete a process of multiple reviews and approvals at both federal and local/institutional levels.

Applications to the following are required:

National Institutes of Health Recombinant DNA Advisory Committee (NIH RAC)

Food and Drug Administration (FDA)

LifeBridge Health Institutional BioSafety Committee (LBH IBC)

LifeBridge Health Institutional Review Board (LBH IRB)

National Institutes of Health (NIH) Guidelines: In undertaking any gene transfer study, PIs should first consult AppendixM of the NIH Guidelines, “Points to Consider in the Design and Submission of Protocols for the Transfer of Recombinant DNA Molecules into One or More Human Research Participants.”

NOTE: These NIH guidelines apply to any research to be conducted at or sponsored by an institution receiving support for recombinant DNA research from NIH. Thus, they apply to all LBH PIs involved in such research.

Application at the Federal Level

Recombinant DNA Advisory Committee (RAC) Review

The NIH Guidelines, Appendix M, outlines the scope of acceptable gene transfer proposals as well as specific review requirements and procedures of the Recombinant DNA Advisory Committee (RAC), within the NIH Office of Biotechnology Activities (OBA).

RAC is a public advisory committee to the Director of NIH; its members include physicians, scientists, medical ethicists, consumer activists, and private citizens, as well as ex officio members of the federal government such as the FDA and the Office of Human Research Protection (OHRP).

The initial RAC review process will include a determination as to whether the study presents characteristics that warrant public RAC review and discussion. RAC may decide that the protocol does not need further in-depth review at a public meeting. However, FDA and local review will still be needed (see below).

Protocols and consent forms should be prepared in accord with NIH Guidelines, Appendix M, sections II-V. In addition to the standard requirements, consent forms must include the following:

PURPOSE: in 6th to 8th grade language.

RISKS:The types, relative severity, and expected frequencies of potential adverse events should be stated. State approximate number of people who have previously received the genetic material under study. Warn potential participants that unforeseen and severe risks are possible for research involving genetic materials previously used in relatively few or no humans. State any potential adverse medical consequences that may occur if the participant withdraws from the study.

REPRODUCTIVE CONSIDERATIONS: Include information concerning possible risks and the need for contraception by males and females during the active phase of the study. The period of time for the use of contraception should be specified and the inclusion of pregnant or lactating women should be addressed.

BENEFITS: For studies that are not reasonably expected to provide a therapeutic benefit to participants, the consent form should clearly state that no direct clinical benefit to participants is expected . . . although knowledge may be gained that may benefit others.

ALTERNATIVES: The consent form should indicate the availability of therapies and the possibility of other investigational interventions and approaches.

LONG TERM FOLLOW-UP: Prospective participants should be informed that they are expected to participate in long-term follow-up that extends beyond the active phase of the study. The consent form should include a list of persons who can be contacted in the event that questions arise during the follow-up period. Require that participants continue to provide a current address and telephone number.

REQUEST FOR AUTOPSY: Participants should be informed that at the time of death, no matter what the cause, permission for an autopsy will be requested of their families. Participants should be asked to advise their families of the request and of its scientific and medical importance.

For more information see:RAC Frequently Asked Questions (FAQs).

NOTE: RAC review must precede local/ institutional review. Any recommendations resulting from the RAC review must be included in the applications to the LBH Institutional BioSafety Committee (IBC) and Institutional Review Board (IRB) (see below).

Who is responsible for the RAC/OBA submission?

For LBH Investigator-initiated (investigator-sponsor) studies (e.g., production of vectors for human application is performed by the LBH investigator), the LBH PI is responsible for the submission of the relevant information on the proposed human gene transfer research to OBA (see directly above).

For Sponsor-initiated studies (e.g., the production of vectors for human application is not performed by the LBH investigator), the Sponsor must complete the RAC submission process and provide the LBH PI with the required Appendix M information for LBH IBC and IRB reviews.

NOTE: In both Investigator-initiated and Sponsor-initiated studies, no participants may be enrolled at an individual site until the OBA has received the following information from the site PI:

Approval from the Institutional BioSafety Committee (IBC), i.e., the LBH IBC;

Approval from the Institutional Review Board (IRB), i.e., the LBH IRB;

LBH IRB-approved informed consent document.

Curriculum vitae of the PI(s) (no more than two pages in biographical sketch format); and

NIH grant number(s) if applicable.

Food and Drug Administration (FDA) Review

The study sponsor or investigator-sponsor will also need to submit an Investigational New Drug (IND) application to the FDA. The IND number will be required for final IRB approval.

Application at the Local (LBH) Level

After the study sponsor or investigator-sponsor has sought initial RAC review and IND approval from the FDA, the LBH PI must apply for institutional review of the gene transfer research.

Institutional BioSafety Committee (IBC): The PI must obtain LBH IBC approval. This committee was established under the NIH Guidelines for Research Involving Recombinant DNA Molecules to provide local review and oversight of nearly all forms of research utilizing recombinant DNA.

Institutional Review Board (IRB): The PI must also obtain approval from the IRBand submit the Human Gene Transfer / Recombinant DNA Research Form.

Applications may be submitted simultaneously to the IBC and IRB for parallel review.

Coordination of Approvals

IRB and IBC: The IRB and IBC will coordinate resolution of any concerns raised by either committee before issuing final authorization and approval. A link will be maintained between the approved IRBand IBC applications for the life of the study.

IRB and FDA: The IRB must receive the IND approval number (obtained from the FDA) before final IRB approval is issued.

IRB, IBC and RAC: A copy of final RAC approval or exemption from review letter should be provided by the PI to the IRB and IBC with the initial application. The IRB will not review the application without this letter.

Copies of LBH IRB and IBC approvals should be provided by the investigator to OBA unless the study is sponsor-initiated, in which case the PI should provide this information to the sponsor for submission to OBA.

Reporting Adverse Events for Human Gene Transfer Studies

The following must be done when an adverse event occurs within a gene transfer study:

The LBH PI must consult and follow policies and procedures for reporting adverse events to the IRB and the IBC (seeLBH Adverse Event Reporting Guidelines for information and forms).

PIs at all sites must report qualifying serious adverse events (SAEs) to the OBA according to the guidance provided in Appendix M-I-C-3 and M-I-C-4 of the NIH Guidelines. PIs may delegate this task to another party (e.g., the sponsor), provided a letter of delegation signed by the PI is on file with the OBA. In either case, any OBA reports concerning LBH-enrolled participants should also be submitted to the LBH IRB and IBC.

If the study IND is held by a LBH investigator (investigator-sponsor), the PI must also report qualifying SAEs directly to the FDA (see 21 CFR 312.32); if the study IND is held by an outside sponsor (sponsor-initiated), this responsibility falls to the sponsor.

LBH IRB Guide #14: Human Gene Transfer/Recombinant DNA Research Page 1 of 4

Version 2, 07-02-10