High density fed-batch cultures for hybridoma cells performed with the aid of a kinetic model

Pörtner, Regina; Schilling, Arndt F.; Lüdemann, Ines; Märkl, Herbert

doi:10.1007/s004490050244

Cited by 5 publications

(10 citation statements)

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“…For example, a promoter specific to G1 phase can cause protein expression to be inversely related to growth . In some cases, specific productivity has been reported to be independent of growth rate, and indeed has been modeled as such by several researchers . To allow for the evaluation of such a scenario, clones were also separately simulated using the following rate of protein expression instead of Equation :

\frac{d c_{P}}{italicdt} = q_{p} x

…”

Section: Methodsmentioning

confidence: 99%

Development of a mathematical model for animal cell culture without pH control and its application for evaluation of clone screening outcomes in shake flask culture

Gadgil

2014

J. Chem. Technol. Biotechnol.

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BACKGROUND: Currently used mathematical models for animal cell growth and metabolism cannot simulate changing culture pH and its effect on metabolism, and hence cannot accurately model cultures lacking pH control. Animal cell cultures are however widely cultured at a small scale without pH control, e.g. for clone screening during cell line development. A mathematical model for animal cell growth without pH control is developed and applied to design optimal conditions for clone screening without pH control.RESULTS: The mathematical model successfully simulates published data for suspension CHO culture in shake flasks. It is further used to simulate clonal heterogeneity and predict relative clone performance in different culture conditions. Predictions of correlation coefficients between clone titers in batch and fed batch screening conditions and pH controlled fed batch agree with published values. Fed batch mode is predicted to give better screening outcomes than batch, but only for clones able to consume lactate. Simulations reveal that culture duration of the screening assay has a large effect on the screening outcome and optimal durations differ based on the ability or inability of clones to consume lactate. CONCLUSION: This study presents a tool for optimal design of screening assay for clone selection without pH control.

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\frac{d c_{P}}{italicdt} = q_{p} x

…”

Section: Methodsmentioning

confidence: 99%

Development of a mathematical model for animal cell culture without pH control and its application for evaluation of clone screening outcomes in shake flask culture

Gadgil

2014

J. Chem. Technol. Biotechnol.

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“…The cells were cultivated in IMDM (Iscove's modified Dulbecco's medium)/Ham's F‐12 or Dulbecco's modified Eagle's medium/Ham's F‐12 respectively as basal medium. Further details are given elsewhere [4,36,37].…”

Section: Methodsmentioning

confidence: 99%

“…The amino acid/vitamin concentrate matches a 10‐fold‐concentrated IMDM/Ham's F‐12 (1:1) medium without salts. In the case of a priori determination, the standard medium was used as feed [37].…”

Section: Methodsmentioning

confidence: 99%

“…The present paper presents a comparison of four different fed‐batch strategies, including fixed feed trajectories, control via the OUR (stoichiometric feeding) [36], a priori determination of feed trajectories based on a kinetic model [37], and the OLFO‐control strategy [4]. The characteristics of the different strategies are illustrated on the basis of one example for each type of cultivation.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of selected control strategies for fed‐batch cultures of a hybridoma cell line

Pörtner

Schwabe

Frahm

2004

Biotech and App Biochem

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While fed-batch suspension culture of animal cells continues to be of industrial importance for the large-scale production of pharmaceutical products, existing control concepts are still insufficient. The present paper illustrates the advantages and disadvantages of different fed-batch strategies, including fixed-feed trajectories, control via OUR (oxygen uptake rate) (stoichiometric feeding), a priori determination of feed trajectories based on a kinetic model and the model-based adaptive OLFO (open-loop-feedback-optimal) control strategy. A recommendation as to which control strategy should be used for a specific process has to consider the respective process. For an established process with a well characterized and stable production cell line, probably the application of a fixed feed trajectory should be recommended. An adaptive, model-based control strategy could be the method of choice during cell-line development or for rapid production of small amounts of product for clinical trials, owing to its universal character and because it does not require intensive process development.

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“…These include the cessation of cell growth, a decline in productivity and specific alterations of protein glycosylation [5]. Thus it is very important to keep the accumulation of growth‐inhibiting metabolites, such as ammonia and lactate, below toxic levels [6].…”

Section: Introductionmentioning

confidence: 99%

A sensitivity analysis of the fed‐batch animal‐cell bioreactor with respect to some control parameters

Lavric

Ofiţeru

Woinaroschy

2005

Biotech and App Biochem

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Animal cell culture is widely used in the manufacture of valuable products, and this process is nowadays seeing a rapid expansion. The growth of animal cells is a complex process, because the cells are very sensitive to environmental changes (in, for example, nutrients, pH, temperature, oxygen and osmolarity) during this phase and to the toxic compounds produced by the cell itself. Ammonia and lactate are the two major waste materials of cell culture. They can have inhibitory effects on cell growth and product (monoclonal antibodies among others) formation. In order to model the behaviour of a fed-batch animal cell bioreactor producing monoclonal antibodies, it is necessary to use a complex kinetic model with optimal operating patterns ensuring high productivities. Good knowledge of such domains of operating parameters, together with the understanding of the response of this rather complex system to small modifications in the working conditions, are essential for on-line control to improve the quality of product and the yield of an animal cell culture. The present study focuses on the sensitivity analysis of a fed-batch animal cell bioreactor with respect to some candidate control parameters (substrate set-point concentrations, feeding time-step patterns and concentration of feeding solutions), emphasizing the influence of these on the overall performance of the system.

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High density fed-batch cultures for hybridoma cells performed with the aid of a kinetic model

Cited by 5 publications

References 0 publications

Development of a mathematical model for animal cell culture without pH control and its application for evaluation of clone screening outcomes in shake flask culture

Development of a mathematical model for animal cell culture without pH control and its application for evaluation of clone screening outcomes in shake flask culture

Evaluation of selected control strategies for fed‐batch cultures of a hybridoma cell line

A sensitivity analysis of the fed‐batch animal‐cell bioreactor with respect to some control parameters

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