Big Changes Coming To Biosafety Oversight of Clinical Gene Transfer

Abstract

To the editor:The director of the National Institutes of Health (NIH), Francis S. Collins, announced on 22 May 2014 that he had accepted the recommendations of a blue-ribbon panel of experts from the Institute of Medicine (IOM) to significantly change the process by which the NIH Recombinant DNA Advisory Committee (RAC) reviews clinical trials involving administration to humans of recombinant or synthetic nucleic acid molecules (recombinant DNA).1xStatement by the NIH Director on the IOM report addressing the role of the Recombinant DNA Advisory Committee in oversight of clinical gene transfer protocols. National Institutes of Health. Collins, FS. See all References This decision was jointly announced, on the same day, by the acting director of the NIH Office of Biotechnology Activities and executive secretary of the RAC, Jacqueline Corrigan-Curay, at the Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). An editorial published in the April issue of Molecular Therapy explained the rationale for the IOM committee's recommendations and encouraged their acceptance by Dr. Collins.2xThe evolution of gene transfer, gene therapy, and the RAC: IOM recommendations to the NIH director. Federoff, HJ and Wagner, JE. Mol Ther. 2014; 22: 685–686Abstract | Full Text | Full Text PDF | PubMed | Scopus (2)See all ReferencesThe RAC, established in 1976 as an advisory committee to the director of the NIH, oversees the NIH Guidelines for Research Involving Recombinant DNA, recently renamed the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acids Molecules (the NIH Guidelines). In the late 1980s, the role of the RAC shifted to being a review body for gene transfer studies in humans. In this role, it reviews the majority of clinical gene transfer studies. RAC review is required if the sponsor or study site receives funding from the NIH that involves recombinant DNA, or if the NIH helped fund the preclinical research that led to the clinical trial. During the intervening years, clinical gene transfer trials that were subject to the NIH Guidelines required review and oversight both at the national level, by the NIH RAC, and at the local level, by institutional biosafety committees (IBCs). The IBCs, which are site-specific, include members who represent the institution as well as members who live in the local community and are not affiliated with the institution.As a result of the advances in the field of clinical gene transfer, the proven safety record for this area of clinical research, and the growing expertise of IBCs at larger research institutions, the IOM report made the following conclusions and recommendations (as presented in Dr. Collins's announcement):“The IOM…concluded that with the evolution of the science, the oversight roles of the RAC, the U.S. Food and Drug Administration (FDA), and institutional oversight authorities have become overlapping and arguably redundant. The IOM's primary recommendation was that the NIH Office of the Director should continue to register all gene transfer protocols and, in consultation with appropriate regulatory and/or oversight authorities, identify protocols for additional public review only if BOTH of the following items are satisfied: 1The protocol review could not be adequately performed by other regulatory and oversight processes (for example, the institutional review boards, IBCs, and the FDA).2One or more of the following criteria are satisfied: The protocol uses a new vector, genetic material, or delivery method that represents a first-in-human experience, thus representing unknown risk; or the protocol relies on preclinical safety data that were obtained using a new preclinical model system of unknown and unconfirmed value; or 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 local and federal regulatory bodies to evaluate the protocol rigorously.”The stated changes will have the effect of transferring primary responsibility of reviewing clinical gene transfer trials for biosafety and for compliance with the NIH Guidelines from the RAC to the local IBCs. The IBCs will then need to either ensure that they have members with appropriate expertise to perform these reviews without input from the RAC or seek outside expertise.Although announced in May, implementation of these changes will take some time. The decision to accept the IOM recommendations and the details of those recommendations were discussed 10 June 2014 at the convened meeting of the RAC, and specific language for the changes will be published in the Federal Register some time thereafter for public comment, before the final changes will be implemented. Members of the gene therapy research and regulatory communities should watch for the Federal Register announcement and be prepared to provide feedback during the public comment period.