Combined effects of potassium chloride and ethanol as mobile phase modulators on hydrophobic interaction and reversed-phase chromatography of three insulin variants

Johansson, Karolina; Frederiksen, Søren Søndergaard; Degerman, Marcus; Breil, Martin Peter; Mollerup, Jørgen; Nilsson, Bernt

doi:10.1016/j.chroma.2014.12.081

Cited by 16 publications

(18 citation statements)

References 47 publications

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“…As demonstrated by Degerman et al and Johansson et al when the UV absorbance is used for model calibration to simulate artificial mixtures of product and impurities, the UV absorbance profile needs to display well pronounced shoulders to allow the simulation of the impurities . Even then, the prediction of variants might still be challenging …”

Section: Resultsmentioning

confidence: 99%

“…However, the elution behavior in RPC can be easily affected, especially by the abovementioned parameters, for example, the effect of potassium chloride or ethanol on the retention. 9 As demonstrated by Degerman et al 29 and Johansson et al 37 when the UV absorbance is used for model calibration to simulate artificial mixtures of product and impurities, the UV absorbance profile needs to display well pronounced shoulders to allow the simulation of the impurities. 29,37 Even then, the prediction of variants might still be challenging.…”

Section: Pooling Decisionmentioning

confidence: 99%

“…9 As demonstrated by Degerman et al 29 and Johansson et al 37 when the UV absorbance is used for model calibration to simulate artificial mixtures of product and impurities, the UV absorbance profile needs to display well pronounced shoulders to allow the simulation of the impurities. 29,37 Even then, the prediction of variants might still be challenging. 38 Instead of using the UV absorbance to calibrate the model, we demonstrate here that by fitting the mechanistic model of RPC to analytical QC data, the elution of the insulin product and, arguably more important, the insulin variants can be predicted.…”

Section: Pooling Decisionmentioning

confidence: 99%

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Model‐based monitoring of industrial reversed phase chromatography to predict insulin variants

Roch

Sellberg

Andersson

et al. 2019

Biotechnology Progress

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Downstream processing in the manufacturing biopharmaceutical industry is a multistep process separating the desired product from process‐ and product‐related impurities. However, removing product‐related impurities, such as product variants, without compromising the product yield or prolonging the process time due to extensive quality control analytics, remains a major challenge. Here, we show how mechanistic model‐based monitoring, based on analytical quality control data, can predict product variants by modeling their chromatographic separation during product polishing with reversed phase chromatography. The system was described by a kinetic dispersive model with a modified Langmuir isotherm. Solely quality control analytical data on product and product variant concentrations were used to calibrate the model. This model‐based monitoring approach was developed for an insulin purification process. Industrial materials were used in the separation of insulin and two insulin variants, one eluting at the product peak front and one eluting at the product peak tail. The model, fitted to analytical data, used one component to simulate each protein, or two components when a peak displayed a shoulder. This monitoring approach allowed the prediction of the elution patterns of insulin and both insulin variants. The results indicate the potential of using model‐based monitoring in downstream polishing at industrial scale to take pooling decisions.

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Section: Resultsmentioning

confidence: 99%

Section: Pooling Decisionmentioning

confidence: 99%

Section: Pooling Decisionmentioning

confidence: 99%

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Model‐based monitoring of industrial reversed phase chromatography to predict insulin variants

Roch

Sellberg

Andersson

et al. 2019

Biotechnology Progress

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“…O etanol é um solvente amplamente utilizado na recuperação e purificação de bioprodutos (RPB), incluindo proteínas. Alguns exemplos do seu uso estão na extração da insulina pancreática animal (ROMANS et al, 1940), na cristalização da pepsina (NORTHROP, 1946), na purificação da álcool desidrogenase de levedura (SCOPES et al, 1981), ou ainda na eluição de proteínas purificadas por cromatografia de fase reversa (JOHANSSON et al, 2015). As moléculas do etanol em solução reduzem a constante dielétrica do meio e competem pela água de hidratação com outros solutos, efeitos que combinados levam à redução da interação de água com moléculas carregadas (SCOPES, 2013).…”

Section: Introductionunclassified

Solubilidade Anômala Da Insulina Em Sistema Água-Etanol

Biaggi¹,

Bernardo²,

Miranda³

2018

Blucher Chemical Engineering Proceedings

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RESUMO -O objetivo do presente trabalho foi determinar a solubilidade da insulina suína em sistema água-etanol. A metodologia se resumiu ao preparo da solução de insulina, sua precipitação com etanol a diferentes concentrações e análise da concentração e perfil eletroforético das proteínas da fase líquida. A curva de solubilidade gerada apresentou um ponto de mínimo nas concentrações próximas à 25% de etanol (v/v), comportamento anômalo possivelmente relacionado com as múltiplas formas associadas que a insulina pode assumir em solução.

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“…The set of parameters associated with the adsorption's dependency on mobile phase concentrations and the properties of the solvent and the stationary phase was calibrated to lab-scale experimental data, to reproduce the behavior in the studied system by means of the inverse method [57][58][59]. A detailed description of the experimental design and the materials used is outlined in [60], and the least-square estimates of the adsorption isotherm kinetics are listed in Table 2. Table 2.…”

Section: Mathematical Modelingmentioning

confidence: 99%

Methods and Tools for Robust Optimal Control of Batch Chromatographic Separation Processes

et al. 2015

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This contribution concerns the development of generic methods and tools for robust optimal control of high-pressure liquid chromatographic separation processes. The proposed methodology exploits a deterministic robust formulation, that employs a linearization of the uncertainty set, based on Lyapunov differential equations to generate optimal elution trajectories in the presence of uncertainty. Computational tractability is obtained by casting the robust counterpart problem in the framework of bilevel optimal control where the upper level concerns forward simulation of the Lyapunov differential equation, and the nominal open-loop optimal control problem augmented with the robustified target component purity inequality constraint margin is considered in the lower level. The lower-level open-loop optimal control problem, constrained by spatially discretized partial differential equations, is transcribed into a finite dimensional nonlinear program using direct collocation, which is then solved by a primal-dual interior point method. The advantages of the robustification strategy are highlighted through the solution of a challenging ternary complex mixture separation problem for a hydrophobic interaction chromatography system. The study shows that penalizing the changes in the zero-order hold control gives optimal solutions with low sensitivity to uncertainty. A key result is that the robustified general elution trajectories outperformed the conventional linear trajectories both in terms of recovery yield and robustness.

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Combined effects of potassium chloride and ethanol as mobile phase modulators on hydrophobic interaction and reversed-phase chromatography of three insulin variants

Cited by 16 publications

References 47 publications

Model‐based monitoring of industrial reversed phase chromatography to predict insulin variants

Model‐based monitoring of industrial reversed phase chromatography to predict insulin variants

Solubilidade Anômala Da Insulina Em Sistema Água-Etanol

Methods and Tools for Robust Optimal Control of Batch Chromatographic Separation Processes

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