Chromatographic separation of three monoclonal antibody variants using multicolumn countercurrent solvent gradient purification (MCSGP)

Müller‐Späth, Thomas; Aumann, Lars; Melter, Lena; Ströhlein, Guido; Morbidelli, Massimo

doi:10.1002/bit.21843

Cited by 116 publications

(58 citation statements)

References 17 publications

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“…11,30,[37][38][39] The model is based on first principles and is using mass balance equations to describe the adsorption process and mass transport within the chromatographic columns. The system dynamics and performance with respect to yield, purity, and productivity are calculated as functions of the process parameters (for more details regarding the mathematical model please see Appendix A).…”

Section: Resultsmentioning

confidence: 99%

“…11,30 More information on the model development and parameters can also be found in 11,31, Aumann et al (2008). 40 Nomenclature for model can be found in Appendix B.…”

Section: Appendix Amentioning

confidence: 99%

“…11,30 The model is based on first principles and follows a lumped-kinetic approach. The model equations are provided in Appendix A.…”

Section: Theoretical Backgroundmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

“…11,30 More information on the model development and parameters can also be found in 11,31, Aumann et al (2008). 40 Nomenclature for model can be found in Appendix B.…”

Section: Appendix Amentioning

confidence: 99%

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Advanced control strategies for the multicolumn countercurrent solvent gradient purification process

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“…Nowadays, there are more gradient variants that allow the variation of solvent elution strength by changing the temperature, pH-value, content of salt, or modifier concentration [89][90][91][92][93][94][95] as well as applications that range from chiral separations, passing by the purification of proteins by ion exchange-SMB (IE-SMB) [96,97], to its use on the old xylene separations [98]. Worth of note is the multicolumn countercurrent solvent gradient purification (MCSGP) process [99][100][101], commercialized by ChromaCon AG (Zürich, Switzerland), which combines two chromatographic separation techniques, i.e., the solvent gradient batch and SMB for the separation of multicomponent mixtures of biomolecules.…”

Section: Gradient Smbmentioning

confidence: 99%

Simulated Moving Bed Chromatography: From Concept to Proof‐of‐Concept

Gomes

Rodrigues

2011

Chem Eng & Technol

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This work presents a comprehensive insight about simulated moving bed (SMB) technology, from concept to unit operation and process demonstration. A particular relevance is given to SMB nonconventional modes of operation, modeling, and design of SMB-based separations as well as to the construction and operation of SMB units. A conventional separation of a racemic mixture of (S,R)-a-tetralol by means of the FlexSMB-LSRE® unit is addressed to better exemplify a state-ofthe-art SMB lab-scale process development and demonstration.

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“…Several techniques have been suggested for the separation of proteins under solvent gradient conditions, e.g., Multi-column Countercurrent Solvent Gradient Purification (MCSGP) [14][15][16][17][18]. The initial MCSGP setup consisted of six columns and was fully continuous.…”

Section: Introductionmentioning

confidence: 99%

Protein separation in carousel multicolumn setup. Performance analysis and experimental validation

Gorczyca

Marek

Bochenek

et al. 2016

Journal of Chromatography A

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Chromatographic separation of three monoclonal antibody variants using multicolumn countercurrent solvent gradient purification (MCSGP)

Cited by 116 publications

References 17 publications

Advanced control strategies for the multicolumn countercurrent solvent gradient purification process

Advanced control strategies for the multicolumn countercurrent solvent gradient purification process

Simulated Moving Bed Chromatography: From Concept to Proof‐of‐Concept

Protein separation in carousel multicolumn setup. Performance analysis and experimental validation

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