Peter Schorn

CHO gene expression profiling in biopharmaceutical process analysis and design

Increase in both productivity and product yields in biopharmaceutical process development with recombinant protein producing mammalian cells can be mainly attributed to the advancements in cell line development, media, and process optimization. Only recently, genome-scale technologies enable a system-level analysis to elucidate the complex biomolecular basis of protein production in mammalian cells promising an increased process understanding and the deduction of knowledge-based approaches for further process optimization. Here, the use of gene expression profiling for the analysis of a low titer (LT) and high titer (HT) fed batch process using the same IgG producing CHO cell line was investigated. We found that gene expression (i) significantly differed in HT versus LT process conditions due to differences in applied chemically defined, serum-free media, (ii) changed over the time course of the fed batch processes, and that (iii) both metabolic pathways and 14 biological functions such as cellular growth or cell death were affected. Furthermore, detailed analysis of metabolism in a standard process format revealed the potential use of transcriptomics for rational media design as is shown for the case of lipid metabolism where the product titer could be increased by about 20% based on a lipid modified basal medium. The results demonstrate that gene expression profiling can be an important tool for mammalian biopharmaceutical process analysis and optimization.

METABOLISCH STRUKTURIERTE MODELLIERUNG UND MODELLGESTUTZTE PROZESSFUHRUNG TIERISCHER ZELLKULTUREN

Dipl.-Ing. Richard Biener arbeitet als Entwicklungsingenieur in der Zentralabteilung Zentrale Technik Technische Entwicklung Abteilung Systemverfahrenstechnik der Bayer AG in Leverkusen. Hauptarbeitsfelder: Modellierung und modellgestützte Prozeßführung verfahrenstechnischer und bioverfahrenstechnischer Systeme. Zur Zeit der Erstellung des Beitrags war er als wissenschaftlicher Mitarbeiter am Institut für Systemdynamik und Regelungstechnik der Universität Stuttgart tätig.

Model-based control of animal cell cultures

A metabolically structured mathematical model was developed. This model describes the dynamics of hybridoma growth and monoclonal antibody production. The model is applied for model-based monitoring and control strategies. It will be demonstrated that for a monoclonal antibody production process the process efficiency can be improved remarkably.