Dataset Information

Kinetic model for adherent Vero cell growth and poliovirus production in batch bioreactors.

ABSTRACT: The production of poliovirus vaccines in adherent Vero cells in batch bioreactors usually consists of a two-step upstream process: (1) Vero cell cultivation on microcarriers and (2) poliovirus proliferation. In this study we developed a mathematical model to describe this two-step process. We introduced the calculation of the oxygen uptake rate (OUR) and a correction of measurement for the sampling effect in order to ensure the high quality data sets. Besides the data of the OUR, we selected glucose concentration, Vero cell concentration and the virus titer for daily in process control to evaluate the progress of the process. With the selected data sets, the described model can accurately describe poliovirus production by Vero cells. Several other regular in process control samples (e.g. lactate concentration, ammonia concentration, and amino acids concentration) were excluded from the model, simplifying the process control analysis and minimizing labor.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC6559155 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Kinetic model for adherent Vero cell growth and poliovirus production in batch bioreactors.

Jiang Yang Y van der Welle Joyce E JE Rubingh Olaf O van Eikenhorst Gerco G Bakker Wilfried A M WAM Thomassen Yvonne E YE

Process biochemistry (Barking, London, England) 20190601

The production of poliovirus vaccines in adherent Vero cells in batch bioreactors usually consists of a two-step upstream process: (1) Vero cell cultivation on microcarriers and (2) poliovirus proliferation. In this study we developed a mathematical model to describe this two-step process. We introduced the calculation of the oxygen uptake rate (OUR) and a correction of measurement for the sampling effect in order to ensure the high quality data sets. Besides the data of the OUR, we selected glu ...[more]

PMID: 31217725

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Project description:Although process intensification by continuous operation has been successfully applied in the chemical industry, the biopharmaceutical industry primarily uses fed-batch, rather than continuous or perfusion methods, to produce stable monoclonal antibodies (mAbs) from Chinese hamster ovary (CHO) cells. Conventional fed-batch bioreactors may start with an inoculation viable cell density (VCD) of ~0.5 × 106 cells/mL. Increasing the inoculation VCD in the fed-batch production bioreactor (referred to as N stage bioreactor) to 2-10 × 106 cells/mL by introducing perfusion operation or process intensification at the seed step (N-1 step) prior to the production bioreactor has recently been used because it increases manufacturing output by shortening cell culture production duration. In this study, we report that increasing the inoculation VCD significantly improved the final titer in fed-batch production within the same 14-day duration for 3 mAbs produced by 3 CHO GS cell lines. We also report that other non-perfusion methods at the N-1 step using either fed batch or batch mode with enriched culture medium can similarly achieve high N-1 final VCD of 22-34 × 106 cells/mL. These non-perfusion N-1 seeds supported inoculation of subsequent production fed-batch production bioreactors at increased inoculation VCD of 3-6 × 106 cells/mL, where these achieved titer and product quality attributes comparable to those inoculated using the perfusion N-1 seeds demonstrated in both 5-L bioreactors, as well as scaled up to 500-L and 1000-L N-stage bioreactors. To operate the N-1 step using batch mode, enrichment of the basal medium was critical at both the N-1 and subsequent intensified fed-batch production steps. The non-perfusion N-1 methodologies reported here are much simpler alternatives in operation for process development, process characterization, and large-scale commercial manufacturing compared to perfusion N-1 seeds that require perfusion equipment, as well as preparation and storage vessels to accommodate large volumes of perfusion media. Although only 3 stable mAbs produced by CHO cell cultures are used in this study, the basic principles of the non-perfusion N-1 seed strategies for shortening seed train and production culture duration or improving titer should be applicable to other protein production by different mammalian cells and other hosts at any scale biologics facilities.

Dataset Information

Kinetic model for adherent Vero cell growth and poliovirus production in batch bioreactors.

Publications

Kinetic model for adherent Vero cell growth and poliovirus production in batch bioreactors.

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