LAPSE:2023.24738
Published Article
LAPSE:2023.24738
PAT for Continuous Chromatography Integrated into Continuous Manufacturing of Biologics towards Autonomous Operation
Florian Lukas Vetter, Steffen Zobel-Roos, Jochen Strube
March 28, 2023
This study proposes a reliable inline PAT concept for the simultaneous monitoring of different product components after chromatography. The feed for purification consisted of four main components, IgG monomer, dimer, and two lower molecular weight components of 4.4 kDa and 1 kDa molecular weight. The proposed measurement setup consists of a UV−VIS diode-array detector and a fluorescence detector. Applying this system, a R2 of 0.93 for the target component, a R2 of 0.67 for the dimer, a R2 of 0.91 for the first side component and a R2 of 0.93 for the second side component is achieved. Root mean square error for IgG monomer was 0.027 g/L, for dimer 0.0047 g/L, for side component 1 0.016 g/L and for the side component 2 0.014 g/L. The proposed measurement concept tracked component concentration reliably down to 0.05 g/L. Zero-point fluctuations were kept within a standard deviation of 0.018 g/L for samples with no IgG concentration but with side components present, allowing a reliable detection of the target component. The main reason inline concentration measurements have not been established yet, is the false-positive measurement of target components when side components are present. This problem was eliminated using the combination of fluorescence and UV−VIS data for the test system. The use of this measurement system is simulated for the test system, allowing an automatic fraction cut at 0.05 g/L. In this simulation a consistent yield of >99% was achieved. Process disturbances for processed feed volume, feed purity and feed IgG concentration can be compensated with this setup. Compared to a timed process control, yield can be increased by up to 12.5%, if unexpected process disturbances occur.
Keywords
attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR), chemometrics, continuous manufacturing, digital twin, diode array detector, fluorescence, integrated counter current chromatography (iCCC), monoclonal antibody (mAB), multivariate data analysis, process analytical technology (PAT), quality by design (QbD), Raman spectroscopy, real-time release testing
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Suggested Citation
Vetter FL, Zobel-Roos S, Strube J. PAT for Continuous Chromatography Integrated into Continuous Manufacturing of Biologics towards Autonomous Operation. (2023). LAPSE:2023.24738
Author Affiliations
Vetter FL: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstraße 15, 38678 Clausthal-Zellerfeld, Germany
Zobel-Roos S: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstraße 15, 38678 Clausthal-Zellerfeld, Germany
Strube J: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstraße 15, 38678 Clausthal-Zellerfeld, Germany
Journal Name
Processes
Volume
9
Issue
3
First Page
472
Year
2021
Publication Date
2021-03-06
Published Version
ISSN
2227-9717
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Original Submission
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PII: pr9030472, Publication Type: Journal Article
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LAPSE:2023.24738
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doi:10.3390/pr9030472
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Mar 28, 2023
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