Model-integrated process development demonstrated on the optimization of a robotic cation exchange step

Osberghaus, Anna; Drechsel, K.; Hansen, Sigrid K.; Hepbildikler, Stefan; Nath, S.; Haindl, Markus; Lieres, Eric von; Hubbuch, Jürgen

doi:10.1016/j.ces.2012.04.004

Cited by 51 publications

(41 citation statements)

References 39 publications

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“…Examples are fluorescent proteins like GFP, YFP, mBanana, tdTomato, mCherry (Shaner et al, 2004), and proteins with chromophore groups like cytochrome c (Osberghaus et al, 2012). Most other proteins, however, are hard to distinguish spectrometrically.…”

Section: Introductionmentioning

confidence: 98%

Integrated development of up- and downstream processes supported by the Cherry-Tag™ for real-time tracking of stability and solubility of proteins

Baumann

Bluthardt

Renner

et al. 2015

Journal of Biotechnology

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Section: Introductionmentioning

confidence: 98%

Integrated development of up- and downstream processes supported by the Cherry-Tag™ for real-time tracking of stability and solubility of proteins

Baumann

Bluthardt

Renner

et al. 2015

Journal of Biotechnology

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“…Combining scale-down experimentation with liquid handling robotics and computational models is considered to be the most promising approach to resolve the downstream bottleneck. The system has also been successfully applied to optimize a cation exchange step [48]. The system has also been successfully applied to optimize a cation exchange step [48].…”

Section: Integration Of Dsp In the Product Development Phasementioning

confidence: 99%

Consistent development of bioprocesses from microliter cultures to the industrial scale

Neubauer

Cruz

Glauche

et al. 2013

Engineering in Life Sciences

105

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Bioprocess development today is slow and expensive compared to chemical process development. A drastic paradigm shift is necessary and possible by the consistent application of engineering strategies that are typically used in the process development phase already in the early product development. Aside from providing a consistent pathway, strategies such as statistical‐based design of experiments, fed‐batch, minibioreactors, new on‐line sensors, process modeling, and control tools in combination with automation of manual steps offer a higher success rate and the opportunity to find the optimum parameters and operation point. This also directly benefits the early phases of biomolecular screening and initial production of small amounts of the target molecule. The paper reviews the bioprocess developmental phases from a business perspective and the available systems and technologies.

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“…For chromatography studies, batch resin slurries in 96‐well plate formats have been well described . More recently, miniature columns using multichannel liquid handlers have also provided valuable information at small scale for guiding process development . Strategies and guidelines for using each of these techniques in process development have also been described .…”

Section: Introductionmentioning

confidence: 99%

High‐throughput techniques to evaluate the effect of ligand density for impurity separations with multimodal cation exchange resins

Welsh

Bao

Barlow

et al. 2015

Engineering in Life Sciences

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High-throughput techniques to evaluate the effect of ligand density for impurity separations with multimodal cation exchange resins Scale-down, high-throughput screening techniques are well on their way to becoming a commodity in downstream bioprocess development, especially for the rapid development of chromatography process steps. This work used both resin slurry plate and miniature column high-throughput screening methodologies to identify the best resin properties for mAb separations utilizing a multimodal chromatography ligand interaction. A ligand with both cation exchange and hydrophobic interaction properties was studied at several ligand densities and compared to a commercially available multimodal resin with a larger particle size at high ligand density. The resins were screened with mAbs containing distinct process impurities (aggregates and a hydrophobic variant), and optimized conditions provided more than a log of clearance of both types of impurities for the different resins screened. These studies reveal that while a smaller particle size is generally preferable, optimal ligand densities can be different depending on the properties of both the mAb and impurity studied.

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Model-integrated process development demonstrated on the optimization of a robotic cation exchange step

Cited by 51 publications

References 39 publications

Integrated development of up- and downstream processes supported by the Cherry-Tag™ for real-time tracking of stability and solubility of proteins

Integrated development of up- and downstream processes supported by the Cherry-Tag™ for real-time tracking of stability and solubility of proteins

Consistent development of bioprocesses from microliter cultures to the industrial scale

High‐throughput techniques to evaluate the effect of ligand density for impurity separations with multimodal cation exchange resins

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