Development of an intermediate chromatography step in an insulin purification process. The use of a High Throughput Process Development approach based on selectivity parameters

Heldin, Eva; Grönlund, Sara; Shanagar, Jamil; Hallgren, Elisabeth; Eriksson, Kjell; Xavier, Mariza; Tunes, Heloisa; Vilela, Luciano

doi:10.1016/j.jchromb.2014.09.024

Cited by 13 publications

(7 citation statements)

References 11 publications

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“…The focus of this paper is on the second of these goals, the identification of effective operating conditions. Such studies are usually based on a Design of Experiments (DoE) structure and High Throughput (HT) methods are often combined with automated equipment, including robotic liquid handlers, to facilitate development . In such an approach, promising conditions are identified via the employment of regression analysis techniques in scouting studies and these are then investigated in detail in follow up optimization studies, also employing a DoE structure.…”

Section: Introductionmentioning

confidence: 99%

Application of simplex‐based experimental optimization to challenging bioprocess development problems: Case studies in downstream processing

Konstantinidis

Welsh

Roush

et al. 2016

Biotechnology Progress

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The identification of feasible operating conditions during the early stages of bioprocess development is implemented frequently through High Throughput (HT) studies. These typically employ techniques based on regression analysis, such as Design of Experiments. In this work, an alternative approach, based on a previously developed variant of the Simplex algorithm, is compared to the conventional regression-based method for three experimental systems involving polishing chromatography and protein refolding. This Simplex algorithm variant was found to be more effective in identifying superior operating conditions, and in fact it reached the global optimum in most cases involving multiple optima. By contrast, the regression-based method often failed to reach the global optimum, and in many cases reached poor operating conditions. The Simplex-based method is further shown to be robust in dealing with noisy experimental data, and requires fewer experiments than regression-based methods to reach favorable operating conditions. The Simplex-variant also lends itself to the use of HT analytical methods, when they are available, which can assist in avoiding analytical bottlenecks. It is suggested that this Simplex-variant is ideally suited to rapid optimization in early-phase process development. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:404-419, 2016.

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Section: Introductionmentioning

confidence: 99%

Application of simplex‐based experimental optimization to challenging bioprocess development problems: Case studies in downstream processing

Konstantinidis

Welsh

Roush

et al. 2016

Biotechnology Progress

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“…Descriptions of scale down chromatography studies have been well described in the literature. Some more recent examples are included .…”

Section: Workflow: What Is Everyday Htpd?mentioning

confidence: 99%

Lessons learned in building high‐throughput process development capabilities

Pollard

McDonald²,

Hesslein

2016

Engineering in Life Sciences

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Companies have adapted high‐throughput techniques for process development to different levels. Some companies are beginning to incorporate high‐throughput process development (HTPD) techniques at a level which is approachable for the beginner user (example: plate‐based resin screening for purification) and others have sophisticated robotic platforms which are in routine use for new pipeline products for upstream, downstream, analytics, and just now starting in the protein formulation area. This mini review serves to summarize how companies have set up and are using HTPD capabilities, including the need for user‐groups to improve the likelihood of success. The focus will be a practical summary of the utility and limitations of these approaches.

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“…HTPD itself just increases the amount of data and enables the creation of black‐box models such as response‐surface models or DoE studies. Although, these empirical models are frequently used with good results, they are restricted with respect to the provided mechanistic process insight . In contrast to mechanistic models, they are not based on first principle natural laws, such as Fick's law of diffusion within a column model and do not allow extrapolation …”

Section: Introductionmentioning

confidence: 99%

A versatile noninvasive method for adsorber quantification in batch and column chromatography based on the ionic capacity

Huuk

Briskot

Hahn

et al. 2016

Biotechnology Progress

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Within the Quality by Design (QbD) framework proposed by the International Conference on Harmonisation (ICH), high-throughput process development (HTPD) and mechanistic modeling are of outstanding importance for future biopharmaceutical chromatography process development. In order to compare the data derived from different column scales or batch chromatographies, the amount of adsorber has to be quantified with the same noninvasive method. Similarly, an important requirement for the implementation of mechanistic modeling is the reliable determination of column characteristics such as the ionic capacity Λ for ion-exchange chromatography with the same method at all scales and formats. We developed a method to determine the ionic capacity in column and batch chromatography, based on the adsorption/desorption of the natural, uv-detectable amino acid histidine. In column chromatography, this method produces results comparable to those of classical acid-base titration. In contrast to acid-base titration, this method can be adapted to robotic batch chromatographic experiments. We are able to convert the adsorber volumes in batch chromatography to the equivalent volume of a compressed column. In a case study, we demonstrate that this method increases the quality of SMA parameters fitted to batch adsorption isotherms, and the capability to predict column breakthrough experiments. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:666-677, 2016.

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Development of an intermediate chromatography step in an insulin purification process. The use of a High Throughput Process Development approach based on selectivity parameters

Cited by 13 publications

References 11 publications

Application of simplex‐based experimental optimization to challenging bioprocess development problems: Case studies in downstream processing

Application of simplex‐based experimental optimization to challenging bioprocess development problems: Case studies in downstream processing

Lessons learned in building high‐throughput process development capabilities

A versatile noninvasive method for adsorber quantification in batch and column chromatography based on the ionic capacity

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