Model-based strategy for cell culture seed train layout verified at lab scale
© Kern et al. 2015
Published: 14 December 2015
Production of biopharmaceuticals for diagnostic and therapeutic applications with suspension cells in bioreactors requires a seed train up to production scale . For the first steps - the transitions between T-flasks, tubes, roller bottles, shake flasks, stirred bioreactors or single-use reactors - the experimental effort to lay-out these steps is high. At the same time it is known that the first cultivation steps have a significant impact on the success or failure in production scale. A software tool has been developed which provides possibilities for simulation, analysis and design of seed trains . Tool structure:
A kinetic model. In this case a simple unstructured model where kinetic parameters can be obtained from a few experiments only.
A Nelder-Mead-algorithm to determine model parameters.
A developed MATLAB software tool able to determine optimal points in time or viable cell concentrations for transfer into the next scale.
The successful application for the cell line (AGE1.HN AAT , ProBioGen AG) has been shown previously . Here the tool was tested for a suspendable CHO cell line.
Materials and methods
The cell line CHO-K1 has been grown in chemically defined TC-42 medium (TeutoCell AG, Bielefeld, Germany), 4 mmol L-1 glutamine.
Data for parameter identification for the kinetic mode were determined in shake flask cultures. The seed train steps were: 1. culture tube (0.0025 L), 2. shake flask (0.070 L), 3: Labfors 5 Cell (2 L).
The concept offers a simple and inexpensive strategy for design of seed train scale-up steps. The results for the lab scale steps show that the tool was able to perform a seed train optimization only on the basis of two batches, the underlying model and its parameter identification.
The bioreactor (Labfors 5 Cell) was kindly provided by the company Infors AG, the suspendable cell line CHO-K1 by Prof. Thomas Noll, University of Bielefeld.
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