Bioprocess Design and Production Technology for the Future

Strube, Jochen; Grote, Florian; Ditz, Reinhard

doi:10.1002/9783527653096.ch20

Cited by 21 publications

(26 citation statements)

References 74 publications

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“…Maturing manufacturing technologies tend to move from batch to continuous operation, often driven by economy-ofscale scenarios. On the other hand, it could be shown that continuous manufacturing of biologics would drastically reduce CAPEX from 250 to 50 million u for typical monoclonal antibody productions at a scale of 1 -3 t a -1 [54]. Investing the same resources could drastically reduce the risk of product failure in clinical trials by simultaneously investing in 5 different products while increasing flexibility at the same time.…”

Section: Proposed Approachmentioning

confidence: 96%

“…Instead of spending about 50 -250 million u for batch multipurpose plants, continuous and product dedicated manufacturing plants in containers with CAPEX in the magnitude of 1 -5 million u seem to be the best technical solution at the moment [54,55]. It could be set up in manufacturing by building infrastructure due to product regulation demands, up to clean rooms and auxiliaries.…”

Section: Proposed Approachmentioning

confidence: 99%

“…Provided that the stratification issue works out, there is higher potential for clinical success, but by definition going along with low volume manufacturing without economy-of-scale potentials. The proposed concept of continuous, nevertheless flexible manufacturing shows significant potential for SMEs [54].…”

Section: Proposed Approachmentioning

confidence: 99%

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Efficient Engineering and Production Concepts for Products in Regulated Environments – Dream or Nightmare?

Strube

Ditz

Fröhlich

et al. 2014

Chemie Ingenieur Technik

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Manufacturing of chemical-pharmaceutical products is moving increasingly fast on a global scale. Therefore, developing and starting up production facilities fast, with high quality, and at reasonable costs has become extremely challenging.Engineering concepts like modularization, standardization and simultaneous/parallel engineering are discussed as methods for speeding up process design and filing for regulatory approval. Transfer from batch to continuous operation mode of production is pointed out as the key-issue in such strategies.

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Section: Proposed Approachmentioning

confidence: 96%

Section: Proposed Approachmentioning

confidence: 99%

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Efficient Engineering and Production Concepts for Products in Regulated Environments – Dream or Nightmare?

Strube

Ditz

Fröhlich

et al. 2014

Chemie Ingenieur Technik

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“…Similarly, in downstream processing and in particular in the case of chromatographic separation processes, it is essential to optimize and/or redesign current equipment to allow handling of larger load volumes, while minimizing equipment and material cost. [10][11][12][13][14] From a process stand point, it is necessary to ensure that the integrated bioprocess is adequately and efficiently monitored and controlled to achieve maximum and stable product quality and yield. Control and monitoring of such complex processes is a challenging task that is now coupled with the continuous operation, rendering online measurements even more challenging to obtain.…”

Section: Introductionmentioning

confidence: 99%

Advanced model‐based control strategies for the intensification of upstream and downstream processing in mAb production

Papathanasiou

Quiroga-Campano

Steinebach

et al. 2017

Biotechnology Progress

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Current industrial trends encourage the development of sustainable, environmentally friendly processes with minimal energy and material consumption. In particular, the increasing market demand in biopharmaceutical industry and the tight regulations in product quality necessitate efficient operating procedures that guarantee products of high purity. In this direction, process intensification via continuous operation paves the way for the development of novel, eco-friendly processes, characterized by higher productivity and lower production costs. This work focuses on the development of advanced control strategies for (i) a cell culture system in a bioreactor and (ii) a semicontinuous purification process. More specifically, we consider a fed-batch culture of GS-NS0 cells and the semicontinuous Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) for the purification process. The controllers are designed following the PAROC framework/software platform and their capabilities are assessed in silico, against the process models. It is demonstrated that the proposed controllers efficiently manage to increase the system productivity, returning strategies that can lead to continuous, stable process operation. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:966-988, 2017.

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“…Under high titers, however, DSP can become significantly expensive, mostly due to equipment and consumables costs. [5][6][7][8][9] This along with the increasing demand on product quality and higher titers 3,5 drive advances in mAb biomanufacturing toward continuous operation. 4 Here, we focus on the development of advanced control strategies for the multicolumn countercurrent solvent gradient purification process (MCSGP), 10 aiming to drive the system toward continuous operation.…”

mentioning

confidence: 99%

Advanced control strategies for the multicolumn countercurrent solvent gradient purification process

et al. 2016

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The multicolumn countercurrent solvent gradient purification process (MCSGP) is a semicontinuous, chromatographic separation process used in the production of monoclonal antibodies) . The process is characterized by high model complexity and periodicity that challenge the development of control strategies, necessary for feasible and efficient operation and essential toward continuous production. A novel approach for the development of control policies for the MCSGP process, which enables efficient continuous process control is presented. Based on a high fidelity model, the recently presented PAROC framework and software platform that allows seamless design and in-silico validation of advanced controllers for complex systems are followed. The controller presented in this work is successfully tested against disturbances and is shown to efficiently capture the process periodic nature. V C 2016 American Institute of Chemical Engineers AIChE J, 62: 2341AIChE J, 62: -2357AIChE J, 62: , 2016 Keywords: process control, continuous biomanufacturing, multiparametric control IntroductionMonoclonal antibodies (mAbs) play a vital role in the treatment of infectious diseases, cancer, and autoimmune diseases.1 They are characterized, however, by high prices (approximately $35000 p/a per patient for mAbs treating cancer conditions) 2 that arise from their high production costs. Although over the past few years their market has been rapidly increasing, 3 the emergence of biosimilars and the introduction of novel therapeutic agents drives their biomanufacturing toward alternative routes of lower operating costs. 4 MAb production consists of the upstream processing (USP), where the cells are cultured and the therapeutic agent is produced, and the downstream processing (DSP) that involves the isolation/ purification steps of the targeted product. Under high titers, however, DSP can become significantly expensive, mostly due to equipment and consumables costs. [5][6][7][8][9] This along with the increasing demand on product quality and higher titers 3,5 drive advances in mAb biomanufacturing toward continuous operation. 4 Here, we focus on the development of advanced control strategies for the multicolumn countercurrent solvent gradient purification process (MCSGP), 10 aiming to drive the system toward continuous operation. MCSGP is a semicontinuous, chromatographic separation process of biomolecules, based on ion-exchange firstly presented by . 11 The process is described by complex partial differential and algebraic equations (PDAEs), involving highly nonlinear terms and is governed by periodic operation profiles that render control studies difficult to perform. There have been several works that have studied the optimization and control of such systems. Degerman et al. (2006) 12 use a nonlinear performed optimization studies on a nonlinear chromatography model to define the optimal operation points that will meet the purity Corresponding concerning this article should be addressed to E. Pistikopoulos at stratos@tamu.edu. constrai...

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Bioprocess Design and Production Technology for the Future

Cited by 21 publications

References 74 publications

Efficient Engineering and Production Concepts for Products in Regulated Environments – Dream or Nightmare?

Efficient Engineering and Production Concepts for Products in Regulated Environments – Dream or Nightmare?

Advanced model‐based control strategies for the intensification of upstream and downstream processing in mAb production

Advanced control strategies for the multicolumn countercurrent solvent gradient purification process

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