Design of high productivity sequential multi-column chromatography for antibody capture

Ng, Candy K.S.; Rousset, Fabien; Valéry, Eric; Bracewell, Daniel G.; Sørensen, Eva

doi:10.1016/j.fbp.2013.10.003

Cited by 76 publications

(31 citation statements)

References 23 publications

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“…In addition to biosimilar competition, the number of blockbuster biologics is expected to decline, which would further increase the pressure on cost of goods manufactured (COGm) . Continuous processing has replaced batch manufacturing in other industries due to its improved efficiency, flexibility, and productivity, and now the biopharmaceutical industry is actively developing continuous manufacturing technologies to achieve these goals …”

Section: Introductionmentioning

confidence: 99%

Implementation of Fully Integrated Continuous Antibody Processing: Effects on Productivity and COGm

Arnold¹,

Lee²,

Rucker-Pezzini³

et al. 2018

Biotechnology Journal

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The changing landscape of the biopharmaceutical market is driving a paradigm shift toward continuous manufacturing. To date, integrated continuous bioprocessing has not been realized as enabling technologies are nascent. In this work, a fully integrated continuous process is successfully demonstrated from pilot scale bioreactor to drug substance. Comparable product quality is observed between the continuous process and a 500 L fed-batch conventional process. The continuous process generated material at a rate of 1 kg of purified mAb every 4 days, achieving a 4.6-fold increase in productivity compared to the fed-batch process A plant throughput analysis using BioSolve software shows that a fed-batch facility with 4 × 12 500 L stainless steel bioreactors and purification train of the corresponding scale can be replaced by a continuous facility consisting of 5 × 2000 L single use bioreactors and smaller purification train, with a cost reduction of 15%.

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Section: Introductionmentioning

confidence: 99%

Implementation of Fully Integrated Continuous Antibody Processing: Effects on Productivity and COGm

Arnold¹,

Lee²,

Rucker-Pezzini³

et al. 2018

Biotechnology Journal

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“…(Arve and Liapis, ; Baur et al, ; Carta and Perez‐Almodovar, ; Kaltenbrunner et al, ). Countercurrent capture processes of mAbs have been successfully implemented using four (Pollock et al, ), three (Godawat et al, ; Mahajan et al, ; Ng et al, ), or only two columns (Angarita et al, ). In addition, a final continuous countercurrent polishing step allows the achievement of higher yield values for a given purity (Gottschlich and Kasche, ; Krättli et al, ).…”

Section: Introductionmentioning

confidence: 99%

Process performance and product quality in an integrated continuous antibody production process

Karst

Steinebach

Šoóš

et al. 2016

Biotech & Bioengineering

124

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Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. In this study, a monoclonal antibody producing CHO cell line was cultured in perfusion mode and connected to a continuous affinity capture step. The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. Thereby, optimal buffer consumption and productivity throughout the process was realized while always maintaining a yield above the target value of 99%. Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 10 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. This study is exemplary for the potential of enhancing product quality control and modulation by integrated continuous manufacturing. Biotechnol. Bioeng. 2017;114: 298-307. © 2016 Wiley Periodicals, Inc.

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“…For polishing steps, multi‐column counter‐current solvent gradient purification (MCSGP) , has been successfully used and displayed superior performance compared to batch chromatography. It has been shown that for protein A capture of mAbs, it can be advantageous to use multi‐column setups, rather than batch chromatography, such as the twin‐column CaptureSMB process (which is semi‐continuous when an interconnected wash is applied) or continuous processes with more columns, such as sequential multi‐column chromatography (SMCC) processes , or periodic counter‐current (PCC) processes with interconnected wash, which are typically run with three or four columns , or the BioSMB process, which uses up to 12 columns . In general, counter‐current chromatography offers several advantages, mainly increased productivity, better resin utilization and smaller specific buffer consumption, but these come at the price of higher hardware complexity and increased investment cost .…”

Section: Introductionmentioning

confidence: 99%

Comparison of batch and continuous multi‐column protein A capture processes by optimal design

Baur

Angarita

Müller‐Späth

et al. 2016

Biotechnology Journal

128

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Multi-column capture processes show several advantages compared to batch capture. It is however not evident how many columns one should use exactly. To investigate this issue, twin-column CaptureSMB, 3- and 4-column periodic counter-current chromatography (PCC) and single column batch capture are numerically optimized and compared in terms of process performance for capturing a monoclonal antibody using protein A chromatography. Optimization is carried out with respect to productivity and capacity utilization (amount of product loaded per cycle compared to the maximum amount possible), while keeping yield and purity constant. For a wide range of process parameters, all three multi-column processes show similar maximum capacity utilization and performed significantly better than batch. When maximizing productivity, the CaptureSMB process shows optimal performance, except at high feed titers, where batch chromatography can reach higher productivity values than the multi-column processes due to the complete decoupling of the loading and elution steps, albeit at a large cost in terms of capacity utilization. In terms of trade-off, i.e. how much the capacity utilization decreases with increasing productivity, CaptureSMB is optimal for low and high feed titers, whereas the 3-column process is optimal in an intermediate region. Using these findings, the most suitable process can be chosen for different production scenarios.

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Design of high productivity sequential multi-column chromatography for antibody capture

Cited by 76 publications

References 23 publications

Implementation of Fully Integrated Continuous Antibody Processing: Effects on Productivity and COGm

Implementation of Fully Integrated Continuous Antibody Processing: Effects on Productivity and COGm

Process performance and product quality in an integrated continuous antibody production process

Comparison of batch and continuous multi‐column protein A capture processes by optimal design

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