Scale-down of CHO cell fed-batch cultures

Xiao Pan

Research output: Thesisinternal PhD, WU


Currently, Chinese Hamster Ovary (CHO) cells are the main expression system used for the production of therapeutic monoclonal antibodies (mAbs). The scale-up of a CHO cell culture process is an important step during the upstream development. A representative lab-scale bioreactor (milli-litres to litres volume) for the production-scale bioreactor (kilo-litres volume) is important for a robust process scale-up. In this thesis, a miniature bioreactor system (ambr® 15, a 15 mL volume system) is used as a scale-down model for a 10 L bench-scale bioreactor system. A thorough characterization of the physiology of the CHO cells, in terms of metabolism and transcriptome, is carried out for the fed-batch process run at both the ambr® 15 and the 10 L scale. The characteristic cell physiology is used in conjugation with the engineering first principles to understand the differences between scales for a cell culture process. The result of this thesis gives a better understanding of cell physiology in fed-batch cultures and on the scale-down of these processes. This knowledge can be used to increase the efficiency of process development and thus shorten the time-to-market for the biopharmaceutical products.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
  • Wijffels, Rene, Promotor
  • Martens, Dirk, Co-promotor
  • Dalm, M.C.F., Co-promotor, External person
Award date29 May 2018
Place of PublicationWageningen
Print ISBNs9789463438438
Publication statusPublished - 29 May 2018


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