A development and control strategy in integrated bioprocessing using concomitant impurity monitoring
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.
We will show case studies of components, mammalian processes and products, in which fingerprints and typical impurities are monitored at line across several unit operations. The benefits of this approach are:
• Identification of point of harvest from the bioreactor along optimization of productivity and product quality objectives.
• Judgement of unit operation performance in harvesting und product isolation, process steps which were hardly assessed so far, due to the high background of impurities.
• In contrast to spectroscopic measurements, HPLC allows identification of the actual components , facilitating also regulatory application.
• Ability to adjust the subsequent unit operation on the basis of a CQA profile as input parameters, leading to a solid control strategy.
• In a mid term perspective, allowing continuous processing solutions.
Presented by
Prof. Dr.-techn. Christoph Herwig,
Professor for Biochemical Engineering, Vienna University of Technology
Christoph Herwig, bioprocess engineer, graduated from the process engineering department, university of technology RWTH Aachen in 1994. He worked in industry in the design and commissioning of large chemical facilities prior to enter his interdisciplinary PhD studies at the University of Technology EPFL, Lausanne Switzerland in the field of bioprocess identification. Subsequently he positioned himself at the interface between bioprocess development and facility design of biopharmaceutical facilities working in different companies from process development over engineering services to biopharmaceutical production.
Since 2008, he has been a full professor for biochemical engineering at the Vienna University of Technology. The research area focuses on the development of method of science based and efficient bioprocess development for biopharmaceuticals along PAT and QbD principles in upstream and downstream within industry driven projects.
