Cedric Schirmer

By Cedric Schirmer, Thomas Nussbaumer, Reto Schöb, Ralf Pörtner, Regine Eibl and Dieter Eibl

Stirred tank bioreactors are still the predominant cultivation systems in large scale biopharmaceutical production. Today, several manufacturers provide both reusable and single-use systems, whereas the broad variety of designs and properties lead to deviations in biological performance. Although the methods for bioreactor characterization are well established, varying experimental conditions and procedures can result in significantly different outcomes. In order to guarantee a reliable comparison and evaluation of different single-use and reusable bioreactor types, standardized methods for their characterization are needed. Equally important is the biological capability of bioreactors, which must be accessed by standardized cultivation procedures of industrially relevant organisms (bacteria, yeasts as well as mammalian and animal cell cultures). In addition, the implementation of well-defined uniform procedures for biological and engineering characterization during the development phase can support a fast assessment of the suitability of a bioreactor system. Based on stirred bioreactors, we describe the aspects of the engineering characterization in order to discuss further the biological characterization as a valuable complement. Finally, a case study is presented.

Part of the book: Biopharmaceuticals

By Stefan Seidel, Cedric Schirmer, Rüdiger W. Maschke, Lia Rossi, Regine Eibl and Dieter Eibl

The first part of this series on characterisation of bioreactors in the biopharmaceutical industry using computational fluid dynamics presented a literature review to illustrate how characterisation can be performed and which process engineering parameters can be determined using computational fluid dynamics (CFD). In addition, experimental validation methods were presented, and an overview of typical hardware and software was also provided. In this second part, a selection of the authors’ research results will be used to demonstrate how the process characterisation of mechanically driven bioreactors for the biopharmaceutical industry can be determined with CFD and then experimentally validated. Three stirred tank bioreactors with different filling volumes and stirrers were used to demonstrate power input and oxygen transfer in single- and two-phase simulations. For wave-mixed and orbitally shaken systems, the fluid flow was transiently simulated and experimentally validated. In addition, the power input was also determined for both systems.

Part of the book: Computational Fluid Dynamics

By Stefan Seidel, Cedric Schirmer, Rüdiger W. Maschke, Lia Rossi, Regine Eibl and Dieter Eibl

Computational fluid dynamics (CFD) is a widely used tool for investigating fluid flows in bioreactors. It has been used in the biopharmaceutical industry for years and has established itself as an important tool for process engineering characterisation. As a result, CFD simulations are increasingly being used to complement classical process engineering investigations in the laboratory with spatially and temporally resolved results, or even replace them when laboratory investigations are not possible. Parameters that can be determined include the specific power input, Kolmogorov length, hydrodynamic stress, mixing time, oxygen transfer rate, and for cultivations with microcarriers, the NS1 criterion. In the first part of this series, a literature review illustrates how these parameters can be determined using CFD and how they can be validated experimentally. In addition, an overview of the hardware and software typically used for bioreactor characterisation will also be provided, including process engineering parameter investigations from the literature. In the second part of this series, the authors’ research results will be used to show how the process engineering characterisation of mechanically driven bioreactors for the biopharmaceutical industry (stirred, orbitally shaken, and wave-mixed) can be determined and validated using CFD.

Part of the book: Computational Fluid Dynamics