Proteomic Time Profiling of Mab Producing CHO Fed-Batch Bioreactor Cultures

The production of recombinant proteins such as monoclonal antibodies (mAbs) is usually based on complex mammalian cell processes. Rising omics technologies have enabled the characterization of manufacturing processes on a molecular level. Getting a deeper insight into cellular mechanisms is crucial for the understanding and optimization of manufacturing processes, which is also highly promoted by regulatory agencies through the Quality by Design (QbD) initiative. In particular, the investigation of proteomic profiling can be helpful for the identification of important up- and down regulated pathways which have an influence on the process performance and quality of the produced biopharmaceuticals.

The time evolution of the intracellular protein abundance of a monoclonal antibody (mAb) producing Chinese hamster ovary cell line during fed-batch cultivation was investigated. Two different reactor scales were compared distinguishing possible scale-dependent differences. Multivariate data analysis (MVDA) such as principal component analysis (PCA) was used to emphasize highly up- or down expressed proteins over time. A classification of important biological functions was performed by gene ontology annotation using the proteins with highest fold-change. Furthermore, profiling of the produced mAb and the corresponding quality attributes on a proteomic level is discussed targeting possible operational changes. Scale and time dependent proteomic profiling in combination with multivariate statistical analysis will be highlighted for future applications.