(567af) Development of a Single Stage Dual-Ligand Monolithic Chromatography for Plasmid Based Vaccine Production

Ongkudon, C. M., Monash University
Danquah, M. K., Monash University

Many of the production schemes employed by cGMP and GCP facilities combined at least three purification steps to achieve a pharmaceutical grade pDNA vaccine. Increasing the number of unit operations results in product loss and cost ineffectiveness. Although the concept of single-stage pDNA vaccine purification has been found to effectively separate supercoiled pDNA, many problems are still encountered such as low purity, low recovery, high salt consumption, need for post-treatment of pDNA vaccine, and instability of biological-based resin in high affinity separation thus making this process not commercially viable. The present work involves a novel process for pDNA measles vaccine production via optimum fed-batch bacterial fermentation and a single-stage chromatographic purification. Current single-stage chromatography involves only one type of chromatographic mechanism (e.g. anion exchange or affinity interaction) in a one-step loading, washing and elution. The chromatographic technology that is developed in this research is based on a dual-ligand monolithic column that exploits different ligand chemistries in a single column whilst keeping the concept of a single-stage process. The complete details of the invention will be discussed in the full article.