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Impact of freeze–thaw processes on monoclonal antibody platform process development

Weber, Dennis 1; Sittig, Christian 1; Hubbuch, Jürgen 1
1 Institut für Bio- und Lebensmitteltechnik (BLT), Karlsruher Institut für Technologie (KIT)

Abstract:

Freezing of cell culture supernatant (CCS) is a standard procedure in process development of monoclonal antibody (mAb) platform processes as up- and downstream development are usually separated. In the manufacturing process of mAb, however, freezing is avoided, which poses the question of comparability and transferability from process development to manufacturing. In this case study, mAb CCS from Chinese hamster ovary (CHO) cells is frozen and thawed in a novel active freezing device and subsequently captured by protein A chromatography. Critical quality attributes such as host cell protein (HCP) concentration and soluble mAb dimer shares have been monitored throughout the case study. Furthermore, cryo-concentration of individual proteins was investigated. The main factors that drive cryo-concentration are diffusion and natural convection. Natural convection in freezing processes was found to increase at warmer freezing temperatures and thus slower freezing, leading to higher concentration gradients from top to bottom of a freezing chamber. The freeze concentration was dependent on protein size and correlated to diffusivity, where smaller proteins are exposed to higher cryo-concentration. ... mehr


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Originalveröffentlichung
DOI: 10.1002/bit.27867
Scopus
Zitationen: 1
Dimensions
Zitationen: 1
Zugehörige Institution(en) am KIT Institut für Bio- und Lebensmitteltechnik (BLT)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 10.2021
Sprache Englisch
Identifikator ISSN: 0006-3592, 1097-0290
KITopen-ID: 1000135474
Erschienen in Biotechnology & bioengineering
Verlag John Wiley and Sons
Band 118
Heft 10
Seiten 3914-3925
Vorab online veröffentlicht am 06.07.2021
Schlagwörter cell culture supernatant, freezing, monoclonal antibody, platform process, process development
Nachgewiesen in Dimensions
Web of Science
Scopus
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