Advantages of Standardization and Large-Scale Manufacturing of Helper Plasmids for Viral Vector Production

Success in gene and cell therapy has increased demand for plasmid DNA used to produce viral vectors, both in quantities for commercial products as well as the breadth of different vectors for the expanding number of programs in development. The data and analysis indicate that standardization and large-scale production of helper plasmids, those that are the same regardless of the specific viral vector produced, represent an opportunity to significantly reduce timeline, cost, and risk. Aldevron has developed processes to quickly produce a set of helper plasmids that consistently generate functional viral vectors, are immediately available for research and clinical production and are free of any royalties or future payments. To meet production scale requirements, our technical operations team has developed and deployed a platform based around a single-use, 300 L fermentation device and process train capable of purifying up to 100 grams of a plasmid in a single processing event. The manufacture of the output from an individual fermentation process can take as little as seven days. Scaling work done in the early engineering phase for this train was integral to the design of a new 70,000 square foot manufacturing plant. The data show that fermentation scalability can support large processing events and the production of optimized helper plasmids can enable high-titer lentiviral vector production. Standardization of lentiviral plasmids supports consistency and efficiency at large scale and across multiple programs. Our data show the scalability of fermentation for a typical plasmid at 30 L and 300 L, with specific yield maintained as scale is increased. The data show the performance of lentiviral vectors produced with optimized plasmids, indicating improved performance over other plasmid systems. The availability, cost, freedom to operate, and consistency of these plasmids will help address the growing demands of cell and gene therapy.