Manufacturing and quality control of plasmid-based gene expression systems.

DNA plasmid-based gene expression systems are being widely investigated for the potential treatment of genetic and acquired disease and for DNA-based vaccination. A number of human clinical trials are in progress using plasmid-based drugs. The regulatory framework that has been applied to biologicals such as recombinant DNA-derived proteins has proven to be generally applicable for regulating plasmid-based drugs as well. This was recently emphasized by the inclusion of therapeutic DNA plasmid products in the U.S. Food and Drug Administration's list of well-characterized biotechnology products. Present techniques for manufacturing and characterizing plasmids have been adapted from large-scale protein purification and from traditional molecular biology. Production of multi-gram quantities of plasmid, at purities of 95% or more, is currently possible, but further development of both manufacturing and analytical techniques is required. This review describes the approaches and methods currently used to manufacture and characterize DNA plasmids for pharmaceutical use, as well as recent changes in the regulatory environment that will impact future development and marketing of plasmids as human drugs.