Feasibility of using continuous chromatography in downstream processing: Comparison of costs and product quality for a hybrid process vs. a conventional batch process

Ötes, Ozan; Flato, Hendrik; Winderl, Johannes; Hubbuch, Jürgen; Capito, Florian

doi:10.1016/j.jbiotec.2017.07.001

Cited by 33 publications

(14 citation statements)

References 21 publications

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“…These savings come entirely from the consumables category, which includes Protein A sorbent and prepacked columns, as well as buffer preparation and storage bags. The Cadence BioSMB system allows for significant increases in sorbent productivity and reductions in buffer utilization over single column chromatography . This translates to reduced Protein A volume and buffer storage requirements over the batch processes.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to enabling continuous operation, the Cadence Acoustic Separator allows for a significant reduction in clarification depth filtration area. The Cadence BioSMB is a form of multi‐column chromatography system that enables continuous operation and reduced sorbent volume via secondary loading columns and parallel column regeneration . The Cadence BioSMB model utilized the same experimental breakthrough data as the batch bind and elute models, but loading was assumed to be 80% of the volume required to reach 10% breakthrough, corresponding to approximately 1% breakthrough.…”

Section: Methodsmentioning

confidence: 99%

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Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales

Hummel

Pagkaliwangan

Gjoka

et al. 2018

Biotechnology Journal

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The biopharmaceutical industry is evolving in response to changing market conditions, including increasing competition and growing pressures to reduce costs. Single-use (SU) technologies and continuous bioprocessing have attracted attention as potential facilitators of cost-optimized manufacturing for monoclonal antibodies. While disposable bioprocessing has been adopted at many scales of manufacturing, continuous bioprocessing has yet to reach the same level of implementation. In this study, the cost of goods of Pall Life Science's integrated, continuous bioprocessing (ICB) platform is modeled, along with that of purification processes in stainless-steel and SU batch formats. All three models include costs associated with downstream processing only. Evaluation of the models across a broad range of clinical and commercial scenarios reveal that the cost savings gained by switching from stainless-steel to SU batch processing are often amplified by continuous operation. The continuous platform exhibits the lowest cost of goods across 78% of all scenarios modeled here, with the SU batch process having the lowest costs in the rest of the cases. The relative savings demonstrated by the continuous process are greatest at the highest feed titers and volumes. These findings indicate that existing and imminent continuous technologies and equipment can become key enablers for more cost effective manufacturing of biopharmaceuticals.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales

Hummel

Pagkaliwangan

Gjoka

et al. 2018

Biotechnology Journal

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“…A hybrid process for continuous multicolmn capture chromatography using the Cadence™ BioSMB system was also designed . The work focused on a four‐column setup and compared data to batch mode experiments by using two mAbs and evaluated the long‐term behavior of SMB purification process during 60 cycles (48 h).…”

Section: Improvements On Process Scalabilitymentioning

confidence: 99%

Protein A chromatography: Challenges and progress in the purification of monoclonal antibodies

Ramos‐de‐la‐Peña

González‐Valdez

Aguilar

2019

J of Separation Science

112

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Antibodies for therapeutic use are being continuously approved and their demand has been steadily growing. As known, the golden standard for monoclonal antibody (mAb) purification is Protein A affinity chromatography, a technology that has gained high interest because of its great performance and capabilities. The main concerns are the elevated resins costs and their limited lifetime compared to other resins (e.g. ion exchange chromatography). Great efforts have been carried out to improve purification conditions, such as resin characterization and designing alkali/acid stable resins with a longer lifetime. Modification of Protein A ligands and alternative formats such as monoliths membranes and microshperes have been tested to increase the purification performance. New technology has been proposed to improve the large‐scale separation; in addition, alternative ligands have been suggested to capture mAbs instead of Protein A ligand; however, most of the information is locked by pharmaceutical companies. This mini review summarizes and describes the advances, results, and impact on the Protein A chromatography purification processing.

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“…Warikoo et al provided the proof of concept for the successful integration of a perfusion bioreactor with a continuous capture step, and this group demonstrated the first fully continuous end‐to‐end production of a monoclonal antibody that integrated a perfusion bioreactor and the downstream operations of affinity capture, viral inactivation, and two ion exchange polishing steps . In recent years, several other groups reported successful strategies for continuous bioprocessing . In addition, modeling studies underlined the potential for economic benefit and delineated decisive factors for significant production cost savings associated with continuous downstream processing …”

Section: Introductionmentioning

confidence: 99%

“…10 In recent years, several other groups reported successful strategies for continuous bioprocessing. [11][12][13][14][15][16][17][18][19][20] In addition, modeling studies underlined the potential for economic benefit and delineated decisive factors for significant production cost savings associated with continuous downstream processing. [21][22][23][24][25][26] In this work, we present the optimization and economic assessment of continuous chromatography in the downstream process of a recombinant enzyme.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of continuous nonaffinity capture chromatography for a recombinant enzyme—optimization for a changing perfusion feedstream and comparison to batch processing

Thompson¹,

Wilson²,

Larkin

et al. 2018

Biotechnology Progress

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This work presents the optimization and critical evaluation of continuous capture chromatography in the downstream process of a recombinant enzyme. For the upstream manufacturing of this molecule, a perfusion process was implemented due to benefits for product quality and productivity. This process is, however, characterized by low titer and significant changes over the course of the harvest duration in terms of active enzyme concentration and impurity content. We evaluated the feasibility and benefits of a continuous capture operation. This case study illustrates the design approach that can be utilized to address challenges presented by a changing feedstream, and the statistical measures that can be employed to characterize and optimize the operating space under material and time constraints. Process economic modeling in conjunction with Monte Carlo simulations indicate that even for a nonaffinity capture step utilizing a relatively cheap ion-exchange resin, the smaller column volume used in a continuous set-up results in cost savings compared to the batch process. We compare this option to the scenario of repeated processing using a small capture column in batch mode. Our analysis establishes that continuous processing becomes economically attractive for processes where only a small portion of the potential column lifetime can be utilized or for column steps with slow mass transport and shallow breakthrough curves. In cases where column breakthrough is sharp and resin lifetime is relatively short, continuous processing may offer an improvement over traditional batch processing, but much of the productivity and cost savings can be realized through repeated column cycling. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018 © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1195-1204, 2018.

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Feasibility of using continuous chromatography in downstream processing: Comparison of costs and product quality for a hybrid process vs. a conventional batch process

Cited by 33 publications

References 21 publications

Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales

Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales

Protein A chromatography: Challenges and progress in the purification of monoclonal antibodies

Evaluation of continuous nonaffinity capture chromatography for a recombinant enzyme—optimization for a changing perfusion feedstream and comparison to batch processing

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