Use of the steric mass action model in ion-exchange chromatographic process development

Iyer, Harish; Tapper, Sarah; Lester, Philip; Wolk, Bradley; Reis, Robert van

doi:10.1016/s0021-9673(98)01002-4

Cited by 38 publications

(18 citation statements)

References 19 publications

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“…WPC should be amenable to some of the standard chromatographic column modeling approaches commonly applied to process chromatography (Ishihara et al, 2007;Iyer et al, 1999;Karlsson et al, 2004). Simplistic modeling of product recovery from column runs based solely on the product isotherm has been useful to predict trends as function of K p , load challenge, and product concentration in the load (data not shown).…”

Section: Nature Of Impurities and Enhanced Removal By Weak Partitionimentioning

confidence: 99%

Weak partitioning chromatography for anion exchange purification of monoclonal antibodies

Kelley

Tobler

Brown

et al. 2008

Biotech & Bioengineering

132

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Weak partitioning chromatography (WPC) is an isocratic chromatographic protein separation method performed under mobile phase conditions where a significant amount of the product protein binds to the resin, well in excess of typical flowthrough operations. The more stringent load and wash conditions lead to improved removal of more tightly binding impurities, although at the cost of a reduction in step yield. The step yield can be restored by extending the column load and incorporating a short wash at the end of the load stage. The use of WPC with anion exchange resins enables a two-column cGMP purification platform to be used for many different mAbs. The operating window for WPC can be easily established using high throughput batch-binding screens. Under conditions that favor very strong product binding, competitive effects from product binding can give rise to a reduction in column loading capacity. Robust performance of WPC anion exchange chromatography has been demonstrated in multiple cGMP mAb purification processes. Excellent clearance of host cell proteins, leached Protein A, DNA, high molecular weight species, and model virus has been achieved.

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Section: Nature Of Impurities and Enhanced Removal By Weak Partitionimentioning

confidence: 99%

Weak partitioning chromatography for anion exchange purification of monoclonal antibodies

Kelley

Tobler

Brown

et al. 2008

Biotech & Bioengineering

132

View full text Add to dashboard Cite

show abstract

“…Broad statistical range in the determination of σ has been reported before in [15,16]. The successful predictions based on the calibrated and verified mechanistic model is a key associated to a model-integrated process development.…”

Section: Results Of the Mechanistic Model 421 Model Calibration Andmentioning

confidence: 72%

“…The general rate model for a chromatographic process includes convective and diffusive flows through porous particles on the column level and imitates mass transfer resistances and surface interactions on particle level. In IEC, an external film surrounding adsorbent particles is commonly presumed to model the movement of components from column to particle level; the sorption of protein on the particle surface can be described by the steric mass-action (SMA) model, developed by Iyer et al [15] and generally used for the modeling of salt gradient elution in IEC, for example in [16].…”

Section: Mechanistic Modeling Of Chromatographymentioning

confidence: 99%

Optimization of Lactoperoxidase and Lactoferrin Separation on an Ion-Exchange Chromatography Step

Faraji¹,

Zhang²,

Ray³

2017

Preprint

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Lactoperoxidase (LP), which is a high-value minor whey protein, has recently drawn extensive attention from research scientists and industry due to its multi-function and potential therapeutic applications. In this study, the separation and optimization of two similar-sized proteins, LP and lactoferrin (LF) were investigated using strong cation exchange column chromatography.Optimization was started with central composite design based experiments to characterize the importance of different decision variables. The three variables used in the optimization were flow rate, length of gradient and final salt concentration in the linear elution gradient step. The obtained empiric functional model represented the effect of the significant factors on the yield as the objective function. Afterwards, the calibrated mechanistic model was employed to predict accurate optimal set of variables. The optimal operating points were found and the results were compared with validation experiments. Predictions respecting yield confirmed a very good agreement with experimental results while keeping purity, a product quality characteristic, equal or above to a predefined value.

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“…The steric factor (σ) had negligible influence on the fitting result; thus it was fixed during the optimization of Equation (8) to previously calibrated values in [32]. Broad statistical range in the determination of σ has been reported before in [21,22]. The successful predictions based on the calibrated and verified mechanistic model is a key associated to a model-integrated process development.…”

Section: Results Of Response Surface Modelingmentioning

confidence: 99%

“…The general rate model for a chromatographic process includes convective and diffusive flows through porous particles on the column level and imitates mass transfer resistances and surface interactions on particle level. In IEC, an external film surrounding adsorbent particles is commonly presumed to model the movement of components from column to particle level; the sorption of protein on the particle surface can be described by the steric mass-action (SMA) model, developed by Iyer et al [21] and generally used for the modeling of salt gradient elution in IEC, for example in [22].…”

Section: Mechanistic Modeling Of Chromatographymentioning

confidence: 99%

Optimization of Lactoperoxidase and Lactoferrin Separation on an Ion-Exchange Chromatography Step

2017

View full text Add to dashboard Cite

Lactoperoxidase (LP), which is a high-value minor whey protein, has recently drawn extensive attention from research scientists and industry due to its multiplicity of function and potential therapeutic applications. In this study, the separation and optimization of two similar-sized proteins, LP and lactoferrin (LF) were investigated using strong cation exchange column chromatography. A two-step optimization strategy was developed for the separation of LP and LF. Optimization was started with central composite design-based experiments to characterize the influences of different decision variables, namely, flow rate, length of gradient, and final salt concentration in the linear elution gradient step on the yield of LP. This was followed by a more accurate optimization of ion-exchange chromatography (IEC) separation of LP and LF based on an experimentally verified chromatographic model. The optimal operating points were found and the results were compared with validation experiments. Predictions respecting yield confirmed a very good agreement with experimental results with improved product purity.

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Use of the steric mass action model in ion-exchange chromatographic process development

Cited by 38 publications

References 19 publications

Weak partitioning chromatography for anion exchange purification of monoclonal antibodies

Weak partitioning chromatography for anion exchange purification of monoclonal antibodies

Optimization of Lactoperoxidase and Lactoferrin Separation on an Ion-Exchange Chromatography Step

Optimization of Lactoperoxidase and Lactoferrin Separation on an Ion-Exchange Chromatography Step

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