REGULATORY REVIEW OF CELLULAR AND GENE THERAPIES - AN OVERVIEW OF THEPROCESS

Cell and gene therapies, using several different approaches, have been proposed for a variety of genetic diseases, cancer and AIDS. The majo r regulatory review process in the US consists of an institutional rev iew board, the recombinant DNA advisory committee (RAC) and the Food a nd Drug Administration (FDA). Within the Center for Biologics Evaluati on 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 con sider'' 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 conc erns common to all biologicals administered to human subjects remain u nchanged. These include safety, efficacy, purity, potency, quality con trol 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 betwee n the sponsor and the FDA prior to the phase I, II and III clinical tr ials. A timely and ongoing evaluation of pre-clinical testing cannot b e overemphasized in this rapidly growing and changing field. The devel opment of a working relationship at this stage will ensure a seamless integration of the IND process with the product and establishment lice nse applications. Because replication-competent retrovirus (RCR) repre sents a potential for pathogenicity, the FDA is recommending a conserv ative approach to RCR testing.