Industrial Manufacturing of Plasmid-DNA Products for Gene Vaccination and Therapy

Although today only a few DNA vaccine products have gained market approval for veterinary applications, still numerous human clinical trials are performed. Clinical progress in the field of DNA vaccination and gene therapy has led to an increased demand of pharmaceutical-grade plasmid DNA (pDNA), manufactured under the conditions of current Good Manufacturing Practices (cGMP). Consequently, significant progress in process science and manufacturing technology of plasmid DNA has been made during the past years. In upstream processing (vector design, host strain, fermentation process), significant achievements have been made, resulting in steadily increasing pDNA fermentation titers. In general, the downstream processing steps such as cell lysis and chromatographic purification still often represent engineering challenges in view of high product scales. This article summarizes the state of the art in industrial plasmid manufacturing and discusses bottlenecks and pitfalls to be avoided in order to obtain pDNA products of high and reproducible quantity and quality.