Skip to main content
Download PDF

Volume 9 Supplement 9

24th European Society for Animal Cell Technology (ESACT) Meeting: C2P2: Cells, Culture, Patients, Products

Media optimization for CHO fed-batch processes using a DoE approach in automated high-throughput single use ambr15 bioreactors

BMC Proceedings volume 9, Article number: P15 (2015) Cite this article

Background

Chinese Hamster Ovary (CHO) derived cells are the most commonly used cell lines for the production of biopharmaceuticals. We developed a plug and play method to optimize the growth medium for a given CHO production cell line. The experiment consists of a Mixture Design of Experiments (DOE) approach using different basal media to select the optimized formulations for a specific CHO cell line. The package for media optimization consists of different base media together with the ambr15 high throughput bioreactor and integrated MODDE DoE software.

Methods and results

A suspension adapted CHO DG44 cell line expressing a monoclonal antibody was used for the experiments. Media mixes composed of differing concentrations of nutrients were used in a mixture DOE with 20 different media and 3 center points. All conditions were inoculated in the ambr at the same starting density of 2.0xE5 cells/mL. Dissolved oxygen, pH, and temperature control were maintained throughout the batch process. Each bioreactor was sampled for cell count and viability. Metabolites as well as IgG titers were measured. Peak Viable Cell Density (VCD), Doubling Time (DT), and IgG titer results were collected and modeled as responses using MODDE 10 design of experiments (DOE) software to evaluate the optimal media mixtures. Results are shown in Figure 1.

Figure 1
figure 1

Contour plot (titer) and optimal mixes: DOE predictions of optimal media mix for titer and media formulations optimized for titer (red star) doubling time (green star) and VCD/Titer/doubling time weighed equally (yellow star) are shown.

Full size image

Conclusions

The ambr15 and MODDE software used here provided a path to obtain effective media formulations for a given specific CHO cell line. The approach consists of a comprehensive service containing four basal media to prepare the mixes and the ambr15. It is supported by an application specialist to guide the experiments and interpretation of results.

Author information

Authors and Affiliations

  1. Lonza Bioscience, Walkersville, MD, 21793, USA

    Alexis Bossie

  2. Sartorius Stedim France S.A.S., 13781, Aubagne, France

    Christophe Grimm & Wolfgang Kusser

  3. Sartorius Stedim North America Inc., Bohemia, NY, 11716, USA

    Brian Lee & Greg Bremer

Authors
  1. Christophe Grimm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wolfgang Kusser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Greg Bremer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alexis Bossie
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Grimm, C., Kusser, W., Lee, B. et al. Media optimization for CHO fed-batch processes using a DoE approach in automated high-throughput single use ambr15 bioreactors. BMC Proc 9 (Suppl 9), P15 (2015). https://doi.org/10.1186/1753-6561-9-S9-P15

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1753-6561-9-S9-P15

Keywords

  • Chinese Hamster Ovary
  • Mixture Design
  • Viable Cell Density
  • Production Cell Line
  • Comprehensive Service

BMC Proceedings

ISSN: 1753-6561

Contact us