Gene Transfer Requirements Relaxed Under NIH Proposal

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By Jeannie Baumann

Oct. 15 — The NIH wants to loosen its oversight of gene transfer studies so that only exceptional cases would need review by a federal advisory committee, according to a Federal Register notice set to be published Oct. 16.

The proposed changes to the National Institutes of Health Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules would implement a policy change announced in May 2014 by NIH Director Francis S. Collins. That change—to require high-level review for only exceptional studies instead of all of them—is based on a 2013 Institute of Medicine report that concluded it's no longer necessary to run every protocol by the NIH's Recombinant DNA Advisory Committee (RAC) because there's a better understanding of the risks associated with gene therapy.

“The IOM noted that the RAC has served a valuable role, but concluded that the current level of oversight over individual clinical trials is no longer justifiable. In an effort to maximize the benefits of the RAC review process, the IOM recommended that the NIH maintain its protocol submission and safety reporting requirements, but restrict individual gene transfer protocol reviews to exceptional cases that meet specified criteria,” the Federal Register notice said.

Past Controversy, Concerns

RAC review of gene transfer studies has been required since 1974, when the NIH established the advisory committee. According to the IOM, the NIH implemented that requirement in response to “discussion and controversy over scientific, research participant safety, ethical, and other societal concerns” over gene transfer studies because scientists had just developed methods for manipulating DNA.

Under the proposed changes, the RAC only would review studies that have been forwarded by an oversight body at a research institution, such as an institutional biosafety committee (IBC) or an institutional review board (IRB), because that oversight body determined the study would benefit significantly from RAC review. The protocol also would have to meet one or more of the following criteria:

• The protocol uses a new vector, genetic material or delivery methodology that represents a first-in-human experience, thus presenting an unknown risk.

• The protocol relies on preclinical safety data obtained using a new preclinical model of unknown and unconfirmed value.

• The proposed vector, gene construct or method of delivery is associated with possible toxicities that aren't widely known and that may render it difficult for oversight bodies to evaluate the protocol rigorously.


The request from the research institution must include a rationale for why the protocol satisfies the criteria triggering RAC review. The NIH said it would make a decision in 10 working days as to whether the study warrants review.

If the NIH denies a RAC review request, the agency said, it would still offer information about previous protocols that have used similar products. But the proposal noted that the NIH still has discretion to select research protocols for review if the agency determines that the study “may present significant scientific, societal, or ethical concerns.”

Registration Changes

The guidelines would still require all human gene transfer protocols to be registered with the NIH, and the principal investigator would continue to be responsible for submitting documentation regarding a proposed human gene transfer protocol to his or her local oversight bodies. The investigator also would be responsible for providing documentation from these bodies regarding whether they think RAC review is warranted.

“If no oversight body requests RAC review, the IBC may proceed with its approval process upon receipt of documentation from the NIH indicating that the protocol registration process is complete,” the Federal Register notice said. No research participant could be enrolled in the gene transfer protocol until the registration process is completed, it added.

If the NIH approves a RAC review request, the IBC couldn't approve that protocol until the RAC review is completed.

The NIH also proposed to reduce how much information investigators need to submit when they register their protocol in an effort to streamline the protocol submission process.

Comments are due Nov. 30 and may be e-mailed to; faxed to (301) 496-9839; or mailed to the Office of Science Policy, National Institutes of Health, 6705 Rockledge Drive, Suite 750, Bethesda, Md., 20892-7985. The NIH said all written comments received in response to this notice will be available for public inspection at the NIH Office of Science Policy and may be posted to the NIH website.

To contact the reporter on this story: Jeannie Baumann in Washington at

To contact the editor responsible for this story: Lee Barnes at

Fore more information, contact the NIH at or (301) 496-9838.

The Federal Register notice is available at

The 2013 Institute of Medicine report is available at

The current guidelines are available at


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