Gene therapeutics and DNA vaccines; quality and regulatory aspects

Transfer of genes to cells and the subsequent expression of these genes can alleviate the symptoms of a disease (gene therapy), or prevent infectious diseases (DNA vaccination). Gene therapy and DNA vaccination are based on relatively new technologies. The first gene therapeutics are expected to enter the market as registered medicinal products within 2-4 years. The vectors used to transfer the gene of interest to target cells are genetically modified viruses or plasmids. Viral vectors and plasmids are produced biotechnologically and are therefore considered to be biological medicinal products ('biologicals'). Since the production of biologicals is inherently variable and difficult to control, these products require extra safety measures and regulations. The Laboratory for Medicines and Medical Devices of the RIVM, involved in the regulatory assessment and control authority batch-release testing of biologicals, has carried out an inventory study on both the analytical methods used for characterisation of viral and plasmid vectors and the regulatory issues affecting these products. The results of this study indicate that many quality and safety considerations applicable to viral and plasmid vectors are identical to those applied to other biologicals. Novel analytical methods are those for testing the identity of the vector, measuring transduction efficiency, testing for replication-competent viruses, assays for particle count and infectious virus titer, as well as tests for genetic and chemical stability and structure of plasmid vectors. These analytical methods are not yet standardised. However, international initiatives have been started for standardisation. Guidelines for the production and characterisation of gene transfer medicinal products, as provided by regulatory agencies like EMEA and FDA, have been formulated in general terms, and remain subject to frequent revision to keep them up-to-date