LAPSE:2023.24751
Published Article
LAPSE:2023.24751
Process Analytical Technology for Precipitation Process Integration into Biologics Manufacturing towards Autonomous Operation—mAb Case Study
Lara Julia Lohmann, Jochen Strube
March 28, 2023
The integration of real time release testing into an advanced process control (APC) concept in combination with digital twins accelerates the process towards autonomous operation. In order to implement this, on the one hand, measurement technology is required that is capable of measuring relevant process data online, and on the other hand, a suitable model must be available to calculate new process parameters from this data, which are then used for process control. Therefore, the feasibility of online measurement techniques including Raman-spectroscopy, attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR), diode array detector (DAD) and fluorescence is demonstrated within the framework of the process analytical technology (PAT) initiative. The best result is achieved by Raman, which reliably detected mAb concentration (R2 of 0.93) and purity (R2 of 0.85) in real time, followed by DAD. Furthermore, the combination of DAD and Raman has been investigated, which provides a promising extension due to the orthogonal measurement methods and higher process robustness. The combination led to a prediction for concentration with a R2 of 0.90 ± 3.9% and for purity of 0.72 ± 4.9%. These data are used to run simulation studies to show the feasibility of process control with a suitable digital twin within the APC concept.
Keywords
attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), chemometrics, continuous manufacturing, digital twin, fluorescence, monoclonal antibody (mAb), multivariate data analysis, process analytical technology (PAT), Raman-spectroscopy, real time release testing
Subject
Suggested Citation
Lohmann LJ, Strube J. Process Analytical Technology for Precipitation Process Integration into Biologics Manufacturing towards Autonomous Operation—mAb Case Study. (2023). LAPSE:2023.24751
Author Affiliations
Lohmann LJ: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany [ORCID]
Strube J: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Journal Name
Processes
Volume
9
Issue
3
First Page
488
Year
2021
Publication Date
2021-03-09
Published Version
ISSN
2227-9717
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Original Submission
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PII: pr9030488, Publication Type: Journal Article
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LAPSE:2023.24751
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doi:10.3390/pr9030488
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Mar 28, 2023
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