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In recent years, the use of hMSCs, which may be isolated from adipose tissue among others, for the treatment of diseases has increased significantly. The cell quantities required for such therapeutic approaches, between 10

In recent years, the use of hMSCs, which may be isolated from adipose tissue among others, for the treatment of diseases has increased significantly. The cell quantities required for such therapeutic approaches, between 1012 and 1013, have thus far been predominantly produced using commercially available multi-tray systems, such as the Cell Factory (Thermo Fisher Scientific) or HYPERStack (Corning), which can be purchased with up to 40 layers. However, the handling of these planar multilayer systems is difficult, and process monitoring opportunities remain limited. Here, automated stirred single-use bioreactors provide a viable alternative to the time-consuming multiplication of cells using such planar systems, while still managing to achieve the desired clinically relevant quantities. In these stirred single-use systems, adherent cells are predominantly cultivated in suspension up to pilot scale using carrier materials, also referred to as microcarriers (MCs).This chapter describes the steps which need to be realized to guarantee successful hMSC expansion within a stirred single-use bioreactor (Eppendorf's BioBLU® 0.3c) operated using MCs under serum- and xeno-free conditions at benchtop scale. The cultivations were performed using an immortalized human adipose-derived mesenchymal stem cell (hASC) line, hence referred to as hASC52telo, and a new chemically defined, xeno-free medium, hence referred to as the UrSuppe formulation. Spinner flask cultivations were performed under comparable process conditions.

Therapeutic monoclonal antibodies (mAbs) are the fastest-growing class of biotherapeutics. They are mainly used to treat cancer, inflammatory, metabolic and autoimmune diseases. Their commercial production processes are mainly based on Chinese hamster ovary (CHO) suspension cells, which are currently cultivated in fed-batch mode at cubic meter scale. The annually growing market for therapeutic mAbs and the pressure on producers to reduce their manufacturing costs have led to the increasing development of intensified and continuous production processes in recent years. Single-use systems are used in both upstream and downstream processing. This book chapter describes the main intensification approaches and operational architectures of continuous processes realized today, based on the developmental status of single-use technologies used for the up- and downstream processing of mAbs. In this context, the terms “process intensification” and “continuous process” are defined, while the preferential application of single-use systems is described using literature, and further by own studies. Based on the findings, the main challenges for the implementation of intensified and continuous mAb production using single-use systems are identified.