LAPSE:2019.1169
Published Article
LAPSE:2019.1169
Distinct and Quantitative Validation Method for Predictive Process Modelling in Preparative Chromatography of Synthetic and Bio-Based Feed Mixtures Following a Quality-by-Design (QbD) Approach
Steffen Zobel-Roos, Mourad Mouellef, Reinhard Ditz, Jochen Strube
November 24, 2019
Process development, especially in regulated industries, where quality-by-design approaches have become a prerequisite, is cost intensive and time consuming. A main factor is the large number of experiments needed. Process modelling can reduce this number significantly by replacing experiments with simulations. However, this requires a validated model. In this paper, a process and model development workflow is presented, which focuses on implementing, parameterizing, and validating the model in four steps. The presented methods are laid out to gain, create, or generate the maximum information and process knowledge needed for successful process development. This includes design of experiments and statistical evaluations showing process robustness, sensitivity of target values to process parameters, and correlations between process and target values. Two case studies are presented. An ion exchange capture step for monoclonal antibodies focusing on high accuracy and low feed consumption; and one case study for small molecules focusing on rapid process development, emphasizing speed of parameter determination.
Keywords
biologics, continuous bioprocessing, manufacturing, Modelling, modular plants, Process Intensification, regulated industry
Suggested Citation
Zobel-Roos S, Mouellef M, Ditz R, Strube J. Distinct and Quantitative Validation Method for Predictive Process Modelling in Preparative Chromatography of Synthetic and Bio-Based Feed Mixtures Following a Quality-by-Design (QbD) Approach. (2019). LAPSE:2019.1169
Author Affiliations
Zobel-Roos S: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstraße 15, D-38678 Clausthal-Zellerfeld, Germany
Mouellef M: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstraße 15, D-38678 Clausthal-Zellerfeld, Germany
Ditz R: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstraße 15, D-38678 Clausthal-Zellerfeld, Germany
Strube J: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstraße 15, D-38678 Clausthal-Zellerfeld, Germany
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Journal Name
Processes
Volume
7
Issue
9
Article Number
E580
Year
2019
Publication Date
2019-09-02
Published Version
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr7090580, Publication Type: Journal Article
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LAPSE:2019.1169
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doi:10.3390/pr7090580
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Nov 24, 2019
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CC BY 4.0
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[v1] (Original Submission)
Nov 24, 2019
 
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Nov 24, 2019
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https://psecommunity.org/LAPSE:2019.1169
 
Original Submitter
Calvin Tsay
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