The advances in gene therapy and genetic vaccination based on plasmid DNA result in an increasing demand of pharmaceutical grade plasmids produced under cGMP. A generic process consisting of a cell disintegration step followed by three different chromatography steps has been developed. Cell lysis is performed by an automated continuous reactor. ne clarified lysate is further purified by hydrophobic interaction, anion exchange, size exclusion chromatography and by an ultra-filtration step. The produced plasmid DNA was up to 98% in the supercoiled form. The final genomic DNA content was lower than 10 mu g/mg plasmid DNA, RNA was not detectable by agarose gel electrophoresis, the protein content was lower than 1 mu g/mg plasmid DNA and the endotoxin content lower than 0.1 mu g/mg plasmid DNA. An overall yield of 50% and higher in the desired final buffer could be obtained. This process is scalable and does not require animal derived materials, detergents or organic solvents, meeting current standards for therapeutic applications.