Gene transfer: regulatory issues and their impact on the clinical investigator and the good manufacturing production facility.

The first human gene-transfer study was submitted to the Recombinant DNA Advisory Committee (RAC) in 1988, thus initiating a new era in clinical research. As per the RAC Website (last updated 22nd November 2002), almost 550 human gene-transfer studies have been submitted to the RAC. However, there are currently no licensed gene-therapy products available in the USA. The natural evolution of the review process to accommodate these novel protocols, as well as the death of Jesse Gelsinger in 1999, have led to significant changes in the initial and ongoing review of gene-transfer studies. However, the basic framework of the review process remains unchanged.Gene-transfer protocols require oversight by the Food and Drug Administration (FDA), the Recombinant DNA Advisory Committee (RAC), the Institutional Biosafety Committee (IBC), and the Institutional Review Board (IRB). Such oversight includes both initial review of the protocol and ongoing review of the study through the review of annual reports, adverse events, and proposed amendments to the study. In addition to such review of the protocol, the product itself is required by the FDA to be prepared under current good manufacturing practices (cGMP). This article discusses both regulatory oversight and current GMP issues in depth.