Regulatory review of cellular and gene therapies: an overview of the process.
Cell and gene therapies, using several different approaches, have been proposed for a variety of genetic diseases, cancer and AIDS. The major regulatory review process in the US consists of an institutional review board, the recombinant DNA advisory committee (RAC) and the Food and Drug Administration (FDA). Within the Center for Biologics Evaluation and Research, the Division of Cellular and Gene Therapies has been formed to primarily review investigational new drug applications (INDs) for cellular and gene therapies. Several appropriate "points to consider" documents have been prepared and the RAC has approved over 40 clinical protocols. Advances in biotechnology and the scientific basis for these advances are changing rapidly. Although a flexible, case-by-case approach is necessitated by these rapid changes, regulatory concerns common to all biologicals administered to human subjects remain unchanged. These include safety, efficacy, purity, potency, quality control and assessment, and reproducibility of individual lots. The goal of the review process is a prompt, complete and meticulous review. The emphasis of a pre-IND meeting is toward a working relationship between the sponsor and the FDA prior to the phase I, II and III clinical trials. A timely and ongoing evaluation of pre-clinical testing cannot be overemphasized in this rapidly growing and changing field. The development of a working relationship at this stage will ensure a seamless integration of the IND process with the product and establishment license applications. Because replication-competent retrovirus (RCR) represents a potential for pathogenicity, the FDA is recommending a conservative approach to RCR testing.
Marti
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Division of Cellular and Gene Therapies, FDA NIH, Rockville, MD 20892, USA.
Bauer
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Puri
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Noguchi
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D000818:Animals; D015316:Genetic Therapy / Q000331:legislation & jurisprudence*; D006801:Humans