Single‐Use Technology: Opportunities in Biopharmaceutical Processes

Jornitz, Maik W.; Szarafinski, Detlev; Peuker, Thorsten

doi:10.1002/9783527653096.ch25

Cited by 3 publications

(3 citation statements)

References 2 publications

(2 reference statements)

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“…A comprehensive package (concept) for continuous production has already been presented in earlier studies ,,, (see Figure ), resulting in drafts for dedicated production systems in a container, into which the concept of iCCC as described before fits in perfectly. − ,,, …”

Section: Equipment Implementationmentioning

confidence: 99%

“…The increasingly smaller and, in the future, even further decreasing number of blockbuster candidates justifying metric tons per year manufacturing capacities in large scale batch plants is no longer an efficient option to deal with the timely and cost-effective production of a manifold of 10–100 kg scale stratified drug candidates. This will force a paradigm shift toward continuous operation of smaller scale dedicated plantswith or without disposable technology. − …”

Section: Introductionmentioning

confidence: 99%

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Design and Operation of Continuous Countercurrent Chromatography in Biotechnological Production

Zobel

Helling

Ditz

et al. 2014

Ind. Eng. Chem. Res.

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Continuous countercurrent chromatography has been established in industrial operations for over six decades and in fine chemical and pharmaceutical industry since the 1990s. In biotechnological processing, the area where chromatography plays a criticaland often multipleroles, implementation is lacking for various reasons. Options are shown to correct this and make continuous countercurrent chromatography a technologically and economically viable option in GMP-regulated processing. Current approaches, with the exception of MCSGP (multicolumn countercurrent solvent gradient purification), just operate a manifold of 2–6 columns in a sequential but batchwise scheduling. Modifications were made to reduce equipment complexity in GMP-regulated manufacturing and to exploit benefits of countercurrent operation for adsorbent and buffer reduction. A solution with only one column and a minimum of valves, pumps, and buffer vessels was developed. The approach also describes integration of two or more chromatography steps in continuous production, both GMP- and biocompatible.

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Section: Equipment Implementationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design and Operation of Continuous Countercurrent Chromatography in Biotechnological Production

Zobel

Helling

Ditz

et al. 2014

Ind. Eng. Chem. Res.

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“…Thus, improvements in chromatographic methods, particularly in the direction of continuous counter-current chromatography, have been targeted. A variety of technologies have been investigated in recent years to replace chromatography, including precipitation [16], membrane adsorbers [17,18], counter-current tangential chromatography [19,20] Review Continuous counter-current chromatography for capture and polishing steps in biopharmaceutical production and single-use systems [21], but will not be discussed here.…”

Section: Introductionmentioning

confidence: 99%

Continuous counter‐current chromatography for capture and polishing steps in biopharmaceutical production

Steinebach

Müller‐Späth²,

Morbidelli

2016

Biotechnology Journal

123

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The economic advantages of continuous processing of biopharmaceuticals, which include smaller equipment and faster, efficient processes, have increased interest in this technology over the past decade. Continuous processes can also improve quality assurance and enable greater controllability, consistent with the quality initiatives of the FDA. Here, we discuss different continuous multi-column chromatography processes. Differences in the capture and polishing steps result in two different types of continuous processes that employ counter-current column movement. Continuous-capture processes are associated with increased productivity per cycle and decreased buffer consumption, whereas the typical purity-yield trade-off of classical batch chromatography can be surmounted by continuous processes for polishing applications. In the context of continuous manufacturing, different but complementary chromatographic columns or devices are typically combined to improve overall process performance and avoid unnecessary product storage. In the following, these various processes, their performances compared with batch processing and resulting product quality are discussed based on a review of the literature. Based on various examples of applications, primarily monoclonal antibody production processes, conclusions are drawn about the future of these continuous-manufacturing technologies.

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Protein a resin lifetime study: Evaluation of protein a resin performance with a model-based approach in continuous capture

Behere

Cha

Yoon

2018

Preparative Biochemistry & Biotechnology

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A modified shrinking core model (MSCM) has been used to describe the mechanism for the degradation of Protein A resin particles taking place under continuous chromatographic operation. The model is based on the hypothetical shrinkage of the boundary layer of the resin particles, which house the active Protein A ligands within their pores. The caustic during the sanitization phase of chromatography has been determined to cause the Protein A ligand degradation. Protein A resins provided by manufacturers possess unique caustic stability, which has been used in MSCM to appraise the ligand degradation. The kinetic model utilized semiempirical parameters including diffusion constant, rate constant, stoichiometric factor, and reaction order. The parameters were estimated from column breakthrough experiments to simulate continuous Protein A chromatography for three distinct resins. The reaction order has been identified as the key parameter for predicting the degradation kinetics. The recorded reaction orders vary for three different resins with the resin B showing the highest reaction order of 4 and lowest being 1.65 for the resin C. The model can predict the effects of caustic on resin performance and displayed that minimal degradation of the resins A and B occurred, when exposed to 0.1 N and 0.2N NaOH, retaining up to 96% binding capacity after 240 cycles. The adsorption study conducted for the resin B demonstrated the dynamic physical and chemical changes transpiring through the life cycle of the resin, further supported the degradation model. The performance data demonstrate that the resin B exhibits the desirable performance, with higher reaction order indicating slower resin degradation, higher binding capacities, and increased sustenance of this binding capacity for extended duration. The degradation model can be extended to build effective cleaning strategies for continuous downstream processing.

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Single‐Use Technology: Opportunities in Biopharmaceutical Processes

Cited by 3 publications

References 2 publications

Design and Operation of Continuous Countercurrent Chromatography in Biotechnological Production

Design and Operation of Continuous Countercurrent Chromatography in Biotechnological Production

Continuous counter‐current chromatography for capture and polishing steps in biopharmaceutical production

Protein a resin lifetime study: Evaluation of protein a resin performance with a model-based approach in continuous capture

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