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Monitoring of ultra- and diafiltration processes by Kalman-filtered Raman measurements

Rolinger, Laura 1; Hubbuch, Jürgen ORCID iD icon 1; Rüdt, Matthias 1
1 Institut für Bio- und Lebensmitteltechnik (BLT), Karlsruher Institut für Technologie (KIT)

Abstract:

Monitoring the protein concentration and buffer composition during the Ultrafiltration/Diafiltration (UF/DF) step enables the further automation of biopharmaceutical production and supports Real-time Release Testing (RTRT). Previously, in-line Ultraviolet (UV) and Infrared (IR) measurements have been used to successfully monitor the protein concentration over a large range. The progress of the diafiltration step has been monitored with density measurements and Infrared Spectroscopy (IR). Raman spectroscopy is capable of measuring both the protein and excipient concentration while being more robust and suitable for production measurements in comparison to Infrared Spectroscopy (IR). Regardless of the spectroscopic sensor used, the low concentration of excipients poses a challenge for the sensors. By combining sensor measurements with a semi-mechanistic model through an Extended Kalman Filter (EKF), the sensitivity to determine the progress of the diafiltration can be improved. In this study, Raman measurements are combined with an EKF for three case studies. The advantages of Kalman-filtered Raman measurements for excipient monitoring are shown in comparison to density measurements. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000155726
Veröffentlicht am 10.02.2023
Originalveröffentlichung
DOI: 10.1007/s00216-022-04477-7
Scopus
Zitationen: 10
Web of Science
Zitationen: 7
Dimensions
Zitationen: 9
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Bio- und Lebensmitteltechnik (BLT)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 02.2023
Sprache Englisch
Identifikator ISSN: 1618-2642, 0016-1152, 0372-7920, 0937-0633, 1432-1130, 1618-2650
KITopen-ID: 1000155726
Erschienen in Analytical and Bioanalytical Chemistry
Verlag Springer-Verlag
Band 415
Heft 5
Seiten 841–854
Vorab online veröffentlicht am 18.01.2023
Schlagwörter UF/DF, PAT, Raman spectroscopy, EKF
Nachgewiesen in Scopus
Dimensions
Web of Science
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