By Professor Christoph Herwig, Vienna University of Technology, Austria
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 from the product quality attributes, such as glycosylation and host cell impurities, and secondly 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.
At the upcoming BioProcess International European Summit 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 and 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.
Key Learning Objectives of this lecture are:
- Move from process parameter to direct critical quality attribute monitoring
- Identify the right harvesting time point in recombinant protein production
- Enable control strategies using CQA PAT tools
- Use CQA analyzers to enable robust integrated bioprocessing
Professor Christoph Herwig is speaking at 3.50pm on Day 3 of the BioProcess International European Summit. See the full agenda and register here.