Lack of RAC
Authors: Michele P. Calos
Journal: Molecular Therapy (2018)

The US NIH formed the Recombinant DNA Advisory Committee (RAC) in 1974 in response to the emerging technology of linking genes from different organisms. This powerful recombinant DNA technology, initiated by the Cohen-Boyer experiments at Stanford, spread rapidly. Concerns grew about the potential dangers to laboratory biosafety as well as possible public health threats posed by inadvertent escape of recombinant molecules from the laboratory. Equally concerning were the novel concepts of gene therapy emerging in the 1980’s, which involved putting chimeric DNA molecules into humans. Thus, all NIH-sponsored clinical gene therapy studies were also subject to review by the RAC panel. The RAC played an important role by providing expert advice to discuss the scientific, safety, and ethical issues posed by gene transfer in humans in a transparent, public forum. RAC review was especially valuable while gene therapy was in its early phase of development and posed many unanswered questions. Combining the expertise of the large RAC panel and the US Food and Drug Administration (FDA) was helpful in working out how gene therapy should be evaluated as well as strategies to maximize patient safety. Through the contributions of numerous laboratories and companies, many of these answers are now known. Over the years, as experience was gained with gene transfer to humans, the RAC continued to exert regulatory oversight over gene therapy experiments. This was in addition to oversight by the FDA, which necessarily regulated all gene transfer to humans. Now, after decades of experience, the NIH has proposed removing RAC review and reporting requirements for clinical gene therapy studies. This move is justified, because the FDA has acquired abundant experience and resources to address the regulatory needs of gene therapy and has the in-house expertise to handle review of gene therapy clinical trials. According to the proposed change, gene therapy would now become like other new therapies seeking regulatory approval for testing, which are subject to FDA approval only, not additional RAC approval. The RAC will continue to be involved in the scientific, safety, and ethical issues associated with emerging biotechnology. The FDA reviews gene therapy applications on a continuous basis, involving hundreds of applications. Many of the applications have become relatively routine, involving previously vetted vector systems and protocols. The NIH had already taken steps in the last few years to streamline RAC review by limiting full review to only those applications that presented exceptional concerns. Since 2016, such applications amounted to just a small percentage of those submitted, indicating that the requirement for RAC review was redundant for the vast majority of gene therapy protocols. For most protocols, RAC review is thus a duplicative step that adds significant time and expense to moving gene therapy trials forward. Preparation of review materials generally requires months of work by many different people, slowing the progress of gene therapies and thus reducing patient access to beneficial treatments. Furthermore, redundant review adds an extra cost burden to the development of gene therapy products. This cost must ultimately be added to the price of the final gene therapy product, another factor that reduces patient access to needed treatments. For these reasons, the American Society of Gene and Cell Therapy supports the elimination of the requirement for RAC review for gene therapy clinical studies and welcomes a regulatory environment with logical and streamlined review procedures. At present, several FDA-approved gene therapy products are available in the US, with the expectation of many more to come in the near future. The easing of duplicative regulatory burdens will encourage the flow of additional gene therapy products to the market. It is important that the FDA be provided with adequate funding to keep up with the growing volume of gene therapy applications. Today’s vectors and protocols are likely to be supplanted in the future by novel approaches and technologies, and unexpected adverse events could arise with new or existing protocols. Thus, as the field evolves, there is a continuing need for transparent expert and public review of the scientific, safety, and ethical issues surrounding gene therapy developments. It is as important as ever to provide appropriate forums for such review, for example, utilizing the FDA Advisory Committee format or panels convened by the NIH. In this way, the field of gene therapy will continue to grow, benefit patients, and contribute to medicine up to its full potential.