Clinical trials utilizing recombinant DNA - Change in registration process

To:       Principal Investigators performing clinical trials

From:  Institutional Biosafety Committee (IBC) and Institutional Review Board (IRB)

On March 22, 2016, The Office of Science Policy at NIH (NIH/OSP) published a Final Action under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines).  Changes outlined in this action involve (1) the criteria for selecting clinical trial protocols for in-depth review by the NIH Recombinant DNA Advisory Committee (RAC) and public discussion; (2) the process by which clinical trials are reviewed and registered with the NIH/OSP; and (3) streamlining the protocol submission requirements under Appendix M‑I‑A.

In brief, Principal Investigators must first register their clinical trial protocol with the local IBC and IRB instead of first submitting the protocol to the RAC.  The IBC and IRB will then collaboratively render opinions on whether the protocol meets one or more of three pre-defined criteria: (1) the protocol uses a new vector, genetic material, or delivery methodology that represents a first-in-human experience, thus presenting an unknown risk; (2) the protocol relies on preclinical safety data that were obtained using a new preclinical model system of unknown and unconfirmed value; or (3) the proposed vector, gene construct, or method of delivery is associated with possible toxicities that are not widely known and that may render it difficult for oversight bodies to evaluate the protocol rigorously.  If one or more of these three criteria are met, the IBC and/or IRB will request full RAC review.  Letter will be sent to the Principal Investigator outlining the results of these reviews. 

The Principal Investigator must then submit the letters from the IBC and IRB, along with additional information as outlined in Appendix M-I-A, to the NIH/OSP.  Even if a protocol does not meet any of the three criteria, the NIH Director may select it for full RAC review if s/he determines that it presents significant scientific, societal, or ethical concerns.  When the protocol registration process with NIH/OSP is complete, an acknowledgement will be sent to the Principal Investigator.  This acknowledgement must be forwarded to the IBC and IRB before final approval may be granted.  Final IRB review and approval will follow IBC approval.

As a result of these changes, the online rDNA Registration Document (rDNARD) will be updated to (1) require that Principal Investigators submit information on whether or not their protocol meets any of the three criteria listed above and (2) revise the required attachments to reflect the change in the NIH/OSP registration procedure. 

The Final Action will go into effect on April 27, 2016.  The full publication of the Final Action can be found at:

Please contact Dr. Haley Sinn, Biosafety Officer (335-9553 or, or Michele Countryman, Director Human Subjects Office (353-4452 or with any questions.