ABSTRACT
In another very recent landmark, the U.S. Department of Agriculture (USDA) has conditionally approved a therapeutic DNA vaccine designed to treat melanoma in dogs (Merial 2007). This extraordinary speed in bringing a product from a totally new class to the marketplace, together with the large number (more than 300) of plasmid biopharmaceuticals undergoing preclinical development and clinical trials makes it clear that other products will soon hit the market. Testing DNA vaccines and other plasmid biopharmaceuticals in clinical trials require large amounts of clinicalgrade plasmid DNA. This demand is expected to increase as more products receive marketing approval. In the specic case of DNA vaccines, a surge in demand is also foreseen in the event of a pandemic inuenza outbreak (Forde, 2005). Though dosage is still an open question, with 4 µg (Drape et al., 2006) to 4,000 µg single doses reported (www.clinicaltrials.gov; clinical trial identier: NCT00408109), an annual demand for 900 million units (the world capacity for u vaccine, Hoare et al. 2005) of a DNA vaccine would require anywhere between 3.6 to 3,600 kg of plasmid DNA. This is well over the multigram capacity claimed by contract manufacturing companies. Furthermore, plasmids are found almost exclusively in bacteria and present unique characteristics that translate into very specic problems that hamper product and process development and keep challenging scientists and engineers.
