Automation of process development in up and downstream of bioprocesses

Automation and miniaturization of process development is the key to accelerate the way to the market and reduce the costs of goods by reducing the need of personnel, material and time throughout process development. Therefore, high effort had been put on the development of high throughput screening systems in up and downstream of bioprocesses within the last decade. While different formats for HTS have been established and evaluated for upstream, only for some operation units in downstream processing appropriate systems have been developed and evaluated so far. Most of the published data are focused on chromatographic process steps with automated HTS for resin screening and working conditions, some are available for IB solubilization, protein refolding and protein extraction by ATPS. Few or no data are available about automation of cell disintegration, capture steps, and protein precipitation. A direct connection of automated process development of fermentations to the subsequent downstream process has not been published so far. The overall goal of present project is reduction of time and costs for process development of biopharmaceuticals compared to conventional screenings. A HT platform enabling the automated screening of the entire bioprocess development steps connecting a HT fermentation platform with automated downstream processing and analytics will be established. This will be done by integration and tech transfer of new unit operations (cell disintegration, IB solubilization as first priority; protein precipitation, ATPS as second priority) into existing HT systems. Furthermore, supplementary analytical methods will be evaluated and integrated into the process development chain. General protocols and working modules for downstream HT systems will be compiled for soluble and insolubly expressed products.