Research involving recombinant or synthetic nucleic acid molecules, human gene transfer research, institutional biosafety committee, IBC, safety and annual reporting, serious adverse events, SAE

4.1.26 Research Involving Recombinant or Synthetic Nucleic Acid Molecules (including Human Gene Transfer Research)

4.1.26.1 Scope and Availability

The NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) (April 2016 or latest revision) apply to all research projects (NIH-funded and non-NIH-funded) that involve recombinant or synthetic nucleic acid molecules and are conducted at or sponsored by an organization that receives NIH support for recombinant or synthetic nucleic acid molecule research. A copy of the NIH Guidelines is available at http://osp.od.nih.gov/office-biotechnology-activities/biosafety/nih-guidelines

According to the NIH Guidelines, recombinant and synthetic nucleic acid molecules are defined as (1) molecules that a) are constructed by joining nucleic acid molecules and b) can replicate in a living cell, i.e. recombinant nucleic acids, or (2) nucleic acid molecules that are chemically or by other means synthesized or amplified, including those that are chemically or otherwise modified but can base pair with naturally occurring nucleic acid molecules, i.e. synthetic nucleic acids, or (3)molecules that result from the replication of those described in (1) or (2). The NIH Guidelines apply to both basic and clinical research studies. Specific guidance for the conduct of human gene transfer studies appears in Appendix M of the NIH Guidelines.

Failure to comply with these requirements may result in suspension or termination of an award for recombinant or synthetic nucleic acid molecule research at the organization, or a requirement for NIH prior approvalWritten approval by an authorized HHS official, e.g., a designated IC GMO, evidencing prior consent before a recipient undertakes certain activities or incurs specific costs (see Administrative Requirements-Changes in Project and Budget-Prior Approval Requirements). of any or all recombinant or synthetic nucleic acid molecule projects at the organization. Two specific requirements of the NIH Guidelines are discussed below, but the recipient should carefully review the NIH Guidelines in their entirety to ensure compliance with all of the requirements for projects involving recombinant or synthetic nucleic acid molecules.

Recombinant or synthetic nucleic acid research involving select agents also is subject to pertinent CDC and USDA regulations, 42 CFR 73, Select Agents and Toxins; and 7 CFR 331 and 9 CFR 121, Possession, Use, and Transfer of Biological Agents and Toxins.

4.1.26.2 Institutional Biosafety Committee

Each organization that conducts research involving recombinant or synthetic nucleic acid molecules, including contractors under grants, must have policies and procedures to ensure compliance with the NIH Guidelines and must establish a standing IBC. The IBC is required to review each proposed project for recombinant or synthetic nucleic acid molecule experiments to ensure that the procedures, project, personnel, and facilities are adequate and in compliance with the NIH Guidelines. Section IV of the NIH Guidelines specifies the composition of IBCs. A roster of the IBC members and biosketches for each member must be submitted to the NIH. At a minimum, the roster should indicate the name of each IBC member, as well as which IBC members are serving as the chairperson, contact person, and, as applicable, experts in biosafety or plant, animal, or human experimentation. Biosketches should include a description of the occupation and professional qualifications of each member. Organizations can register their IBC with NIH on-line by utilizing the IBC Registration Management System (RMS). IBC-RMS can be accessed at: http://ibc-rms.od.nih.gov

4.1.26.3 Investigators and Institutional Staff

Section IV of the NIH Guidelines also specifies the roles and responsibilities of PIs, biological safety officers (BSOs) and recipient institutions with respect to the safe conduct and oversight of recombinant or synthetic nucleic acid research. Investigators, laboratory staff, BSOs, and institutional officials should read and be aware of their duties and expected biosafety practices, as described by the NIH Guidelines.

4.1.26.4 Safety and Annual Reporting

Appendix M-I-C-4 of the NIH Guidelines requires PIs to report serious adverse events (SAEs) that are both unexpected and possibly associated with the human gene transfer product to the NIH Office of Science Policy - Biosafety, Biosecurity, and Emerging Biotechnology Policy Division and the IBC as soon as possible but no later than 15 calendar days after the sponsor's initial receipt of the information (i.e., at the same time the event must be reported to the FDA). SAEs that are also fatal or life-threatening must be reported no later than seven calendar days. In addition, investigators must submit to OBA annual reports covering certain information about the protocol. Further information about the content of these reports can be found in Appendix M-I-C-3 of the NIH Guidelines. Investigators may use the GeMCRIS database (http://www.gemcris.od.nih.gov/) as an electronic tool to report adverse events or annual reports on human gene transfer trials to NIH OBA.