LAPSE:2023.24989
Published Article
LAPSE:2023.24989
Towards Autonomous Operation by Advanced Process Control—Process Analytical Technology for Continuous Biologics Antibody Manufacturing
March 28, 2023
Continuous manufacturing opens up new operation windows with improved product quality in contrast to documented lot deviations in batch or fed-batch operations. A more sophisticated process control strategy is needed to adjust operation parameters and keep product quality constant during long-term operations. In the present study, the applicability of a combination of spectroscopic methods was evaluated to enable Advanced Process Control (APC) in continuous manufacturing by Process Analytical Technology (PAT). In upstream processing (USP) and aqueous two-phase extraction (ATPE), Raman-, Fourier-transformed infrared (FTIR), fluorescence- and ultraviolet/visible- (UV/Vis) spectroscopy have been successfully applied for titer and purity prediction. Raman spectroscopy was the most versatile and robust method in USP, ATPE, and precipitation and is therefore recommended as primary PAT. In later process stages, the combination of UV/Vis and fluorescence spectroscopy was able to overcome difficulties in titer and purity prediction induced by overlapping side component spectra. Based on the developed spectroscopic predictions, dynamic control of unit operations was demonstrated in sophisticated simulation studies. A PAT development workflow for holistic process development was proposed.
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Keywords
attenuated total reflection fourier-transformed infrared spectroscopy (ATR-FTIR), chemometrics, Chinese hamster ovary (CHO), continuous manufacturing, digital twin, diode array detector, fluorescence, monoclonal antibody (mAb), multivariate data analysis, process analytical technology (PAT), quality by design (QbD), raman spectroscopy, real time release testing (RTRT)
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Suggested Citation
Helgers H, Schmidt A, Lohmann LJ, Vetter FL, Juckers A, Jensch C, Mouellef M, Zobel-Roos S, Strube J. Towards Autonomous Operation by Advanced Process Control—Process Analytical Technology for Continuous Biologics Antibody Manufacturing. (2023). LAPSE:2023.24989
Author Affiliations
Helgers H: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Schmidt A: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany [ORCID]
Lohmann LJ: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany [ORCID]
Vetter FL: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Juckers A: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Jensch C: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Mouellef M: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Zobel-Roos S: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Strube J: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Schmidt A: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany [ORCID]
Lohmann LJ: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany [ORCID]
Vetter FL: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Juckers A: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Jensch C: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Mouellef M: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Zobel-Roos S: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Strube J: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Journal Name
Processes
Volume
9
Issue
1
First Page
pr9010172
Year
2021
Publication Date
2021-01-18
Published Version
ISSN
2227-9717
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PII: pr9010172, Publication Type: Journal Article
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LAPSE:2023.24989
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doi:10.3390/pr9010172
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Mar 28, 2023
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