Integration of scale-down experimentation and general rate modelling to predict manufacturing scale chromatographic separations

Gerontas, Spyridon; Asplund, Magnus; Hjorth, Rolf; Bracewell, Daniel G.

doi:10.1016/j.chroma.2010.08.063

Cited by 36 publications

(7 citation statements)

References 27 publications

(35 reference statements)

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“…20–25 Once best estimates of the binding parameters (maximum capacity q max,n , adsorption coefficient k ads,n , and desorption coefficient k d,n ) of the protein, which gave the closest prediction, based on the least square method, of the experimental breakthrough curve for a given flow rate were determined, these were then fixed and the completed model was used to simulate breakthrough curves at various other operating flow rates. The predictive capability of this method at various scales has been demonstrated by Gerontas et al26…”

Section: Methodsmentioning

confidence: 92%

Demonstration of the use of windows of operation to visualize the effects of fouling on the performance of a chromatographic step

Boushaba¹,

Baldascini²,

Gerontas³

et al. 2011

Biotechnology Progress

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The high resolution afforded by packed bed chromatography makes it an indispensable operation in the downstream processing of therapeutic molecules. Packed bed performance is however inherently susceptible to changes in feed stream characteristics and fouling processes. The impact of fouling is seldom considered during the early stages of bioprocess development which is concerned with the selection of purification conditions. Instead these are performed with rigorously clarified feeds. Under such conditions, chromatography is effectively treated as an isolated step, independent from its preceding unit operations. In this study, we demonstrate how windows of operation could be used to visualize the impact of changes in the preceding clarification step on the fouling response of a subsequent cation exchange capture step. Laboratory columns (2,5 and 12 cm height) were subjected to varying fouling challenges of Escherichia coli lysate containing different amounts of solids carried over from the previous step. Changes in trans-column pressure drop and breakthrough of the target protein (Fab') were monitored. The limits of operability of the resin were determined with respect to the process material's properties. This information was used to extract the parameters for the adsorption kinetics used in the general rate (GR) model to create windows of operation for manufacturing scale operation.

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Section: Methodsmentioning

confidence: 92%

Demonstration of the use of windows of operation to visualize the effects of fouling on the performance of a chromatographic step

Boushaba¹,

Baldascini²,

Gerontas³

et al. 2011

Biotechnology Progress

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“…The separation of proteins by packed bed chromatography depends on the differences in the mass and binding affinity or charge [29]. The limitations of packed bed chromatography include a high pressure drop across the packed bed, slow film and pore diffusions, a difficulty in packing the column, and a complicated scale-up [30,31]. In contrast to the packed bed column, the characteristics of the monolith-based separation process are a laminar convective mass transfer, a higher dynamic binding capacity with a solute, an easy scale-up, and a high rate of solute recovery.…”

Section: Introductionmentioning

confidence: 99%

Membrane Chromatography and Fractionation of Proteins from Whey—A Review

et al. 2022

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Membrane chromatography (MC) is an emerging bioseparation technology combining the principles of membrane filtration and chromatography. In this process, one type of molecule is adsorbed in the stationary phase, whereas the other type of molecule is passed through the membrane pores without affecting the adsorbed molecule. In subsequent the step, the adsorbed molecule is recovered by an elution buffer with a unique ionic strength and pH. Functionalized microfiltration membranes are usually used in radial flow, axial flow, and lateral flow membrane modules in MC systems. In the MC process, the transport of a solute to a stationary phase is mainly achieved through convection and minimum pore diffusion. Therefore, mass transfer resistance and pressure drop become insignificant. Other characteristics of MC systems are a minimum clogging tendency in the stationary phase, the capability of operating with a high mobile phase flow rate, and the disposable (short term) application of stationary phase. The development and application of MC systems for the fractionation of individual proteins from whey for investigation and industrial-scale production are promising. A significant income from individual whey proteins together with the marketing of dairy foods may provide a new commercial outlook in dairy industry. In this review, information about the development of a MC system and its applications for the fractionation of individual protein from whey are presented in comprehensive manner.

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“…In this context, mathematical models can immensely reduce the number of experiments to be performed and can strategically guide process development and optimization [13] [6], resulting in accelerated development time scales and robust processes. Furthermore, mathematical models are promising tools to support scale-up [14] as well as operation in the manufacturing phase. In combination with UV or Raman sensors, they can be used to monitor breakthrough [15], resin aging [16], and in advanced control schemes [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Hybrid Models for the simulation and prediction of chromatographic processes for protein capture

Narayanan

Seidler

Luna

et al. 2021

Journal of Chromatography A

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Integration of scale-down experimentation and general rate modelling to predict manufacturing scale chromatographic separations

Cited by 36 publications

References 27 publications

Demonstration of the use of windows of operation to visualize the effects of fouling on the performance of a chromatographic step

Demonstration of the use of windows of operation to visualize the effects of fouling on the performance of a chromatographic step

Membrane Chromatography and Fractionation of Proteins from Whey—A Review

Hybrid Models for the simulation and prediction of chromatographic processes for protein capture

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