Process Analytical Technology (PAT): Batch-to-batch reproducibility of fermentation processes by robust process operational design and control

Gnoth, Stefan; Jenzsch, Marco; Simutis, Rimvydas; Lübbert, Α.

doi:10.1016/j.jbiotec.2007.03.020

Cited by 103 publications

(58 citation statements)

References 16 publications

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“…Realtime measurements are important for this key parameter [Gnoth et al, 2007]. Today, several in-line measurement methods are available to determine cell number and cell size distributions in biological processes.…”

Section: Cell and Biomass Concentrationmentioning

confidence: 99%

Process control in cell culture technology using dielectric spectroscopy

Justice¹,

Brix

Freimark³

et al. 2011

Biotechnology Advances

106

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Section: Cell and Biomass Concentrationmentioning

confidence: 99%

Process control in cell culture technology using dielectric spectroscopy

Justice¹,

Brix

Freimark³

et al. 2011

Biotechnology Advances

106

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“…In reality, unknown disturbances are often experienced in the process inputs/outputs of a plant, which affect the product quality. Therefore, the use of control strategies has been suggested within the PAT guidelines [2] to ensure that the process variable(s) follows the desired trajectory [12]. The importance of process control in continuous manufacturing schemes for pharmaceutical operations has been discussed in detail in the scientific literature [6,13,14].…”

Section: Introduction and Objectivementioning

confidence: 99%

A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

2014

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Abstract:In this work, a hybrid MPC (model predictive control)-PID (proportional-integral-derivative) control system has been designed for the continuous purification and processing framework of active pharmaceutical ingredients (APIs). The specific unit operations associated with the purification and processing of API have been developed from first-principles and connected in a continuous framework in the form of a flowsheet model. These integrated unit operations are highly interactive along with the presence of process delays.Therefore, a hybrid MPC-PID is a promising alternative to achieve the desired control loop performance as mandated by the regulatory authorities. The integrated flowsheet model has been simulated in gPROMS TM (Process System Enterprise, London, UK). This flowsheet model has been linearized in order to design the control scheme. The ability to track the set point and reject disturbances has been evaluated. A comparative study between the performance of the hybrid MPC-PID and a PID-only control scheme has been presented. The results show that an enhanced control loop performance can be obtained under the hybrid control scheme and demonstrate that such a scheme has high potential in improving the efficiency of pharmaceutical manufacturing operations.

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“…Here we used glutamine limitation. The production processes should be run in the fed-batch mode, not only in order to increase productivity and to prevent the formation of inhibiting overflow metabolites (Butler 2005;Kuwae et al 2005;Xie and Wang 2006;Ansorge et al 2010;Gnoth et al 2007) but also to increase process reproducibility.…”

Section: Introductionmentioning

confidence: 99%

Increasing batch-to-batch reproducibility of CHO cultures by robust open-loop control

et al. 2010

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In order to guarantee the quality of recombinant therapeutic proteins produced in mammalian cell systems, the straightforward approach in industry is to run the processes as reproducible as possible. It is first shown that considerable distortions in the currently operated processes appear when the initial cell density deviates from its nominal value. Small deviations in the initial cell mass may lead to severe deviations from the desired biomass trajectory. Next, it is shown how to design a fed-batch production process in such a way that it is robust with respect to variations in the viable cell density. A simple open loop strategy is proposed for that purpose. Here we show for the first time at animal cell cultures (CHO cells) that by means of an appropriate glutamine feed rate profile F(t), which keeps the specific growth rate of the cells on a predefined value below its maximal value while maintaining the viabilities on a high level, the diverging viable cell count profiles change over into a robust converging set of profiles. The CHO cells used to validate the procedure could be focused to any specific growth rates below l max .

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Process Analytical Technology (PAT): Batch-to-batch reproducibility of fermentation processes by robust process operational design and control

Cited by 103 publications

References 16 publications

Process control in cell culture technology using dielectric spectroscopy

Process control in cell culture technology using dielectric spectroscopy

A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

Increasing batch-to-batch reproducibility of CHO cultures by robust open-loop control

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