Phenomena and Modeling of Hydrophobic Interaction Chromatography

Borrmann, C.; Helling, C.; Lohrmann, Martin; Sommerfeld, Sven D.; Strube, Jochen

doi:10.1080/01496395.2011.561515

Cited by 18 publications

(13 citation statements)

References 31 publications

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“…16 depicts the results of a study for a direct integration of ion exchange and subsequent hydrophobic interaction chromatography in MAB purification [40].…”

Section: Process Integrationmentioning

confidence: 99%

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Process Development and Design of Downstream Processes

Strube¹,

Grote²,

Josch³

et al. 2011

Chemie Ingenieur Technik

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State-of-the-art of process development, scale-up and design for downstream processes is described for complex mixtures in biotechnology. The focus is on fermentation broth and plant-based extracts to derive methodological arguments. Academic and industrial approaches are discussed with an assessment based on some process relevant criteria. Examples of monoclonal antibody, insulin and penicillin production processes are chosen to develop a sound argumentative basis.Demands of total process integration, accuracy and sensitivity of phenomena, resulting e.g. in miniaturization of laboratory experiments and linked with necessary in-depth modeling are developed and implemented. Specific tasks of unit operation are displayed and their integration into an efficient process sequence is demonstrated. Based on that, further research needs are pointed out and corresponding activities are identified. For instance, the transfer of well established methods in chemical engineering like process modeling in combination with laboratory scale experiments and final miniplant validation should be followed consequently also in biotechnology applications. Some drawbacks in academic education and industrial training as well as organizational structures are discussed to help address this issue.

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“…16 depicts the results of a study for a direct integration of ion exchange and subsequent hydrophobic interaction chromatography in MAB purification [40].…”

Section: Process Integrationmentioning

confidence: 99%

“…The pathway with a protein unfolding step seems to be favored over the direct adsorption mechanism marked in gray. Possible driving forces for the unfolding and adsorption are a salting out effect and the entropic preferred desorption of highly ordered water from the adsorbens [40].…”

Section: Chromatographymentioning

confidence: 99%

Process Development and Design of Downstream Processes

Strube¹,

Grote²,

Josch³

et al. 2011

Chemie Ingenieur Technik

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“…Since characterization for mass transfer by a constant radial concentration distribution leads to insuffi cient simulation results, a detailed physicochemical model considers pore diffusion in the adsorbent [22] :…”

Section: Modelingmentioning

confidence: 99%

“…In the ranking of sensitivity, fl uid dynamics and mass transfer kinetics have to considered appropriately accurate [22] . In the ranking of sensitivity, fl uid dynamics and mass transfer kinetics have to considered appropriately accurate [22] .…”

Section: Experimental Model Parameter Determinationmentioning

confidence: 99%

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Modeling and Experimental Model Parameter Determination with Quality by Design for Bioprocesses

Helling

Strube

2012

Biopharmaceutical Production Technology

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Process development and design in a strictly regulated environment need effi cient methods to generate product quality as early as possible, and to prove the reproducibility and reliability of process operation at the production scale afterwards. For pharmaceuticals, regulatory authorities like US Food and Drug Administration ( FDA ) and European Medicines Agency (EMA) have demanded Quality by Design ( QbD ) approaches in order to fi le information -based decisions. This chapter describes the state -of -the -art of QbD by statistical design of experiments. and actual developments to improve the predictive power and accuracy in combination with a reduction of later efforts by physicochemical -based process modeling. The benefi ts are pointed out exemplifi ed by an examplea typical hydrophobic interaction chromatography step in monoclonal antibody ( mAb ) downstream processing.A model has to be generated that is suffi ciently predictive within a given process operation parameter range with a known suffi cient accuracy. Therefore, a physicochemical -based mathematical process model is derived including nonidealities like fl uid dynamics by axial dispersion, mass transfer kinetics by fi lm and pore diffusion, and multicomponent equilibrium phase by interferences.The model parameters are determined experimentally at the laboratory scale (about a few milliliters) in order to gain an acceptable experimental error of lower then ± 5%. The model ' s accuracy is defi ned with the aid of Monte -Carlo simulations, which are described in detail. Afterwards, the model is validated at the laboratory scale and production scale with a set of different operation parameters to determine the predictive range and accuracy. Finally, some parameter studies are described in order to illustrate the method, discuss benefi ts, and point out limitations.

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