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In silico process characterization for biopharmaceutical development following the quality by design concept

Saleh, David 1; Wang, Gang; Rischawy, Federico 1; Kluters, Simon; Studts, Joey; Hubbuch, Jürgen ORCID iD icon 1
1 Institut für Bio- und Lebensmitteltechnik (BLT), Karlsruher Institut für Technologie (KIT)


With the quality by design (QbD) initiative, regulatory authorities demand a consistent drug quality originating from a well-understood manufacturing process. This study demonstrates the application of a previously published mechanistic chromatography model to the in silico process characterization (PCS) of a monoclonal antibody polishing step. The proposed modeling workflow covered the main tasks of traditional PCS studies following the QbD principles, including criticality assessment of 11 process parameters and establishment of their proven acceptable ranges of operation. Analyzing effects of multi-variate sampling of process parameters on the purification outcome allowed identification of the edge-of-failure. Experimental validation of in silico results demanded approximately 75% less experiments compared to a purely wet-lab based PCS study. Stochastic simulation, considering the measured variances of process parameters and loading material composition, was used to estimate the capability of the process to meet the acceptance criteria for critical quality attributes and key performance indicators. The proposed workflow enables the implementation of digital process twins as QbD tool for improved development of biopharmaceutical manufacturing processes.

Verlagsausgabe §
DOI: 10.5445/IR/1000136907
Veröffentlicht am 30.08.2021
DOI: 10.1002/btpr.3196
Zitationen: 16
Web of Science
Zitationen: 13
Zitationen: 18
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Bio- und Lebensmitteltechnik (BLT)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 8756-7938, 1520-6033
KITopen-ID: 1000136907
Erschienen in Biotechnology progress
Verlag John Wiley and Sons
Band 37
Heft 6
Seiten e3196
Vorab online veröffentlicht am 05.08.2021
Nachgewiesen in Dimensions
Web of Science
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