S16: Implementation of Automated Scale-down Bioreactors for Rapid Process Optimisation and Development

The drive in industrial biotechnology and biopharmaceutical production to reduce time to market for new products means that research and development processes must constantly be updated through the introduction of new technologies and practices.  Two critical activities that must be undertaken early in development for candidate products are cell line selection and process optimisation, both are demanding on development resources and impact the duration of development. It is important that the final outcome is a cell line and process combination that is both robust and appropriate for manufacturing scale.  A number of strategies have been implemented across the industry to ensure that these processes are addressed in an efficient manner, e.g. high throughput cell line screening and platform technologies, however there can still be a disconnect between the optimal conditions identified in the early stages of development and those eventually used in large-scale manufacture. 

We have developed a single-use bioreactor technology (ambr250™) that provides automated operation of 24 bioreactors and rapid turnaround (less than 24 hrs) between fermentations. Proven to mimic larger-scale bioreactors using E.coli, yeast, filamentous and mammalian cell lines the system constitutes a valuable tool for rapid process development.  The core fermentation technology combined with a fully specified bioreactor station; automated feeding and sampling; and offgas analysis for each bioreactor provides a powerful tool for statistically defined process development and QbD approaches for identifying critical parameters.