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Towards Autonomous Operation by Advanced Process Control—Process Analytical Technology for Continuous Biologics Antibody Manufacturing

Helgers, Heribert, Schmidt, Axel, Lohmann, Lara Julia, Vetter, Florian Lukas, Juckers, Alex, Jensch, Christoph, Mouellef, Mourad, Zobel-Roos, Steffen +1 more·2021·Processes
DOI 10.3390/pr9010172
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Abstract

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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  • Helgers et al. demonstrated the integration of various spectroscopic techniques, including Raman, FTIR, fluorescence spectroscopy and UV-Vis, with a predictive modelling data workflow and DT to achieve advanced process control.

    “Helgers et al. demonstrated the integration of various spectroscopic techniques, including Raman, FTIR, fluorescence spectroscopy and UV‐Vis, with a predictive modelling data workflow and DT to achieve advanced process control (APC) [115].”

    From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [115]

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Cited by

Sorted by citations

Authors
Helgers, H., Schmidt, A., Lohmann, L. J., Vetter, F. L., Juckers, A., Jensch, C., Mouellef, M., Zobel-Roos, S., & Strube, J.
Affiliations
Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
ORCID
Venue
Processes
Publisher
MDPI AG
Published
2021-01-18
Volume
9
Issue
1
Pages
172
ISSN
2227-9717
DOI
10.3390/pr9010172
Cited by
50
References
4
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Bundesministerium für Wirtschaft und Energie (03ET1365A)

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