P97: Micro-scale to industrial scale fermentation : implementation of scale-down and DOE combination for process modelisation and improvement of industrial scale vaccine process

For some targets, vaccine manufacturing makes uses of purified antigens derived from fermentation of wild type pathogenic bacterial strain. The design and control of the fermentation process parameters is critical to ensure a sustained and reproducible output of product as well as consistent level of purity. To study and improve culture parameters of an established industrial process (1000L) a culture scale down model at very low scale (3 ml) has been set up. Having first demonstrated equivalency between 1000L bioreactor and 3ml scale down model, a DOE approach was used to generate modelisation of antigen production and impurity profiles within defined domain of culture parameters. Following data output analysis, optimal parameters values were identified and implemented, achieving significant increase of productivity while maintaining within acceptable limits the level of impurities.
This new process design setup has been tested at intermediary bioreactor scale (1-100L) and then further implemented at the 1000L industrial scale.