Continuous countercurrent tangential chromatography for mixed mode post-capture operations in monoclonal antibody purification

Dutta, Amit Kumar; Fedorenko, Dmitriy; Tan, Jasmine; Costanzo, Joseph A.; Kahn, David; Zydney, Andrew L.; Shinkazh, Oleg

doi:10.1016/j.chroma.2017.06.018

Cited by 15 publications

(8 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The optimized continuous countercurrent tangential chromatography method increases yield and productivity compared to traditional batch protein A chromatography and also reduces the protein aggregation with the same amount of contamination removal in the outlet product [41,112]. There are plans to scale up to a commercial scale system [113], but the larger static mixer and filtration membranes [114] have to be further developed to maintain the consumable costs competitively. For non-chromatography methods, ATPS can also achieve continuous protein primary capture with up to 80% global recovery yield and can achieve protein purity more than 99% [115].…”

Section: Discussionmentioning

confidence: 99%

Economic Analysis of Batch and Continuous Biopharmaceutical Antibody Production: a Review

Qadan

Ierapetritou

2019

J Pharm Innov

View full text Add to dashboard Cite

Purpose: There is a growing interest in continuous biopharmaceutical processing due to the advantages of small footprint, increased productivity, consistent product quality, high process flexibility and robustness, facility cost-effectiveness, and reduced capital and operating cost. To support the decision making of biopharmaceutical manufacturing, comparisons between conventional batch and continuous processing are provided. Methods: Various process unit operations in different operating modes are summarized. Software implementation, as well as computational methods used, are analyzed pointing to the advantages and disadvantages that have been highlighted in the literature. Economic analysis methods and their applications in different parts of the processes are also discussed with examples from publications in the last decade. Results: The results of the comparison between batch and continuous process operation alternatives are discussed. Possible improvements in process design and analysis are recommended. The methods used here do not reflect Lilly's cost structures or economic evaluation methods. Conclusion: This paper provides a review of the work that has been published in the literature on computational process design and economic analysis methods on continuous biopharmaceutical antibody production and its comparison with a conventional batch process.

show abstract

Section: Discussionmentioning

confidence: 99%

Economic Analysis of Batch and Continuous Biopharmaceutical Antibody Production: a Review

Qadan

Ierapetritou

2019

J Pharm Innov

View full text Add to dashboard Cite

show abstract

“…The two important parameters for each step are the number of stages and the ratio of the permeate/retentate flow ( γ ) in that stage, both of which affect the product yield (in the elution step) and the degree of impurity removal (in the washing and strip steps). It has been shown in previous publications (Dutta et al, ) that the critical flux is usually >650 L·m −2 ·hr ‐1 (LMH) for the typical operating conditions used in the CCTC system; this was also true for the smaller Resin 2. The required membrane surface area for each hollow fiber module was chosen so that the permeate flux was <50% of the critical flux (giving an upper limit of 325 L·m −2 ·hr ‐1 ).…”

Section: Resultsmentioning

confidence: 69%

“…Continuous countercurrent tangential chromatography (CCTC) provides an attractive alternative to batch column chromatography (Dutta et al, ; Dutta, Tan, Napadensky, Zydney, & Shinkazh, ; Napadensky, Shinkazh, Teella, & Zydney, ; Shinkazh et al, ). The system performs the chromatographic operations (binding, wash, elution, strip, and equilibration) sequentially, with each step composed of multiple stages consisting of hollow fiber membranes and static mixers.…”

Section: Introductionmentioning

confidence: 99%

“…(b) CCTC uses countercurrent staging, with the buffer and resin flowing in opposite directions to increase separation efficiency. (c) CCTC uses the resin as a slurry, significantly reducing the pressure drop in the CCTC system relative to packed columns (typically <15 psi), enabling the flow path to be manufactured with standard tubing and off‐the‐shelf disposable plastic materials (Dutta et al, ). This eliminates the need for any complex cleaning or sanitization cycles and is ideal for integration in single‐use manufacturing facilities.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Improved protein A resin for antibody capture in a continuous countercurrent tangential chromatography system

Fedorenko

Dutta

Tan

et al. 2019

Biotech & Bioengineering

Self Cite

View full text Add to dashboard Cite

Continuous countercurrent tangential chromatography (CCTC) enables steady-state continuous bioprocessing with low-pressure operation and high productivity. CCTC has been applied to initial capture of monoclonal antibodies (mAb) from clarified cell culture harvest and postcapture polishing of mAb; however, these studies were performed with commercial chromatography resins designed for conventional column chromatography. In this study, a small particle size prototype agarose resin (20-25 µm) with lower cross-linking was co-developed with industrial partner Purolite and tested with CCTC. Due to increased binding capacity and faster kinetics, the resulting CCTC process showed more than a 2X increase in productivity, and a 2X reduction in buffer consumption over commercial protein A resins used in previous CCTC studies, as well as more than a 10X productivity increase versus conventional column operation. Single-pass tangential flow filtration was integrated with the CCTC system, enabling simple control of eluate concentration. A scaleup exercise was conducted to provide a quantitative comparison of CCTC and batch column chromatography. These results clearly demonstrate opportunities for using otherwise unpackable soft small particle size resins with CCTC as the core of a continuous bioprocessing platform. K E Y W O R D Santibody, continuous chromatography, protein A, purification, single-use

show abstract

“…An integrated two-stage chromatographic process platform containing CEX and MM was used for the separation of charge variants and aggregates for three different mAbs, and it was found that the required aggregate (<1%), HCP (<10 ppm), and DNA (<5 ppb) clearance was achieved (Kateja et al, 2017b). CCT chromatography was also used for a postcapture antibody purification step using MM resins (CEX-HIC) and showed a 5% increase in yield with similar contaminant removal (Dutta et al, 2017). In another study, it was established that the chromatography resin in a two-column continuous system resulted in 2.5-fold more utilization in comparison with single column batch system (Steinebach et al, 2016;Bielser et al, 2018).…”

Section: Continuous Chromatographymentioning

confidence: 99%

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Tripathi

Shrivastava

2019

Front. Bioeng. Biotechnol.

397

243

View full text Add to dashboard Cite

Infectious diseases, along with cancers, are among the main causes of death among humans worldwide. The production of therapeutic proteins for treating diseases at large scale for millions of individuals is one of the essential needs of mankind. Recent progress in the area of recombinant DNA technologies has paved the way to producing recombinant proteins that can be used as therapeutics, vaccines, and diagnostic reagents. Recombinant proteins for these applications are mainly produced using prokaryotic and eukaryotic expression host systems such as mammalian cells, bacteria, yeast, insect cells, and transgenic plants at laboratory scale as well as in large-scale settings. The development of efficient bioprocessing strategies is crucial for industrial production of recombinant proteins of therapeutic and prophylactic importance. Recently, advances have been made in the various areas of bioprocessing and are being utilized to develop effective processes for producing recombinant proteins. These include the use of high-throughput devices for effective bioprocess optimization and of disposable systems, continuous upstream processing, continuous chromatography, integrated continuous bioprocessing, Quality by Design, and process analytical technologies to achieve quality product with higher yield. This review summarizes recent developments in the bioprocessing of recombinant proteins, including in various expression systems, bioprocess development, and the upstream and downstream processing of recombinant proteins.

show abstract

Continuous countercurrent tangential chromatography for mixed mode post-capture operations in monoclonal antibody purification

Cited by 15 publications

References 17 publications

Economic Analysis of Batch and Continuous Biopharmaceutical Antibody Production: a Review

Economic Analysis of Batch and Continuous Biopharmaceutical Antibody Production: a Review

Improved protein A resin for antibody capture in a continuous countercurrent tangential chromatography system

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Contact Info

Product

Resources

About