Presented by: Uni. Prof. Dr. Christoph Herwig
Vienna University of Technology
The development and control of biopharmaceutical processes is still a time extensive and complex task. This is mainly due to the fact that the developers face complexity originating on the one hand from the product quality attributes, such as glycosylation and host cell impurities, and on the other hand from the process and the biological catalyst, such as pH, feed rates, reaction kinetics and side products.
Following Quality by Design principles, a robust process is obtained if the link between the Critical Quality Attributes (CQA) and the Critical Process Parameters (CPP) is known (design space) and can be controlled (control space). As of today, however, the measurement of the CQAs is hardly available in a timely controlled way, so that for control purposes mainly CPPs are used.
This contribution proposes a novel approach using direct measurements of CQAs. We propose a CQA analyzer, which is based on a HPLC principle combined monolithic columns, which is used horizontally along the entire process, from upstream to downstream processing. Together with advanced multivariate data analysis algorithms, the chromatogram can be used as a fingerprinting method, allowing to track host cell impurities CQAs in a timely controlled way. Hence we present a PAT tool as per original definition.
A development and scale up strategy in downstream processing using concomitant impurity monitoring from BIA Separations on Vimeo.