Optimization study on periodic counter-current chromatography integrated in a monoclonal antibody downstream process

Gomis-Fons, Joaqúın; Andersson, Niklas; Nilsson, Bernt

doi:10.1016/j.chroma.2020.461055

Cited by 42 publications

(35 citation statements)

References 24 publications

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“…The setup was an adaptation of that used previously (Gomis‐Fons et al, 2020); the main difference being the inclusion of continuous virus inactivation with solvent/detergent before the capture step (see Figure 2). In this setup, the capture columns used in the PCC operation were loaded directly from the virus inactivation reactor (red line in Figure 2).…”

Section: Methodsmentioning

confidence: 99%

“…The cycle time must be equal to, or longer than, the recovery time, based on the continuity constraint (Godawat et al, 2012). In this case, the capture and polishing steps were run simultaneously, and therefore the minimum cycle time was determined by the longest recovery time of these steps, as described previously (Gomis‐Fons et al, 2020). By determining the flow rate in this way, at least the same yield and resin utilization as we obtained previously could be obtained at the minimum cycle time (Löfgren et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

“…The position of the three capture columns is changed between each cycle. See Godawat et al (2012) or Gomis‐Fons et al (2020) for further details.…”

Section: The Case Studiedmentioning

confidence: 99%

“…Two of the three capture columns in the PCC operation are interconnected during the loading phase so that the product breakthrough from the first column is adsorbed on the second column, thus allowing the resin utilization to be increased without reducing the yield (Godawat et al, 2012; Gomis‐Fons et al, 2020). At the same time, a third capture column carries out washing, elution, regeneration and equilibration phases (recovery phases).…”

Section: The Case Studiedmentioning

confidence: 99%

See 3 more Smart Citations

An integrated continuous downstream process with real‐time control: A case study with periodic countercurrent chromatography and continuous virus inactivation

Löfgren

Gomis-Fons

Andersson

et al. 2021

Biotech & Bioengineering

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Integrated continuous downstream processes with process analytical technology offer a promising opportunity to reduce production costs and increase process flexibility and adaptability. In this case study, an integrated continuous process was used to purify a recombinant protein on laboratory scale in a two‐system setup that can be used as a general downstream setup offering multiproduct and multipurpose manufacturing capabilities. The process consisted of continuous solvent/detergent virus inactivation followed by periodic countercurrent chromatography in the capture step, and a final chromatographic polishing step. A real‐time controller was implemented to ensure stable operation by adapting the downstream process to external changes. A concentration disturbance was introduced to test the controller. After the disturbance was applied, the product output recovered within 6 h, showing the effectiveness of the controller. In a comparison of the process with and without the controller, the product output per cycle increased by 27%, the resin utilization increased from 71.4% to 87.9%, and the specific buffer consumption was decreased by 21% with the controller, while maintaining a similar yield and purity as in the process without the disturbance. In addition, the integrated continuous process outperformed the batch process, increasing the productivity by 95% and the yield by 28%.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The position of the three capture columns is changed between each cycle. See Godawat et al (2012) or Gomis‐Fons et al (2020) for further details.…”

Section: The Case Studiedmentioning

confidence: 99%

Section: The Case Studiedmentioning

confidence: 99%

See 2 more Smart Citations

An integrated continuous downstream process with real‐time control: A case study with periodic countercurrent chromatography and continuous virus inactivation

Löfgren

Gomis-Fons

Andersson

et al. 2021

Biotech & Bioengineering

Self Cite

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“…The CCC methods are the most widely used in the field of pharmaceutical and natural product analytical and preparative-scale separations (alkaloids, peptides, drugs, chiral compounds, etc.) [ 17 , 27 , 28 , 29 , 30 , 38 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ,…”

Section: Introductionmentioning

confidence: 99%

Analytical, Preparative, and Industrial-Scale Separation of Substances by Methods of Countercurrent Liquid-Liquid Chromatography

2020

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Countercurrent liquid-liquid chromatographic techniques (CCC), similar to solvent extraction, are based on the different distribution of compounds between two immiscible liquids and have been most widely used in natural product separations. Due to its high load capacity, low solvent consumption, the diversity of separation methods, and easy scale-up, CCC provides an attractive tool to obtain pure compounds in the analytical, preparative, and industrial-scale separations. This review focuses on the steady-state and non-steady-state CCC separations ranging from conventional CCC to more novel methods such as different modifications of dual mode, closed-loop recycling, and closed-loop recycling dual modes. The design and modeling of various embodiments of CCC separation processes have been described.

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Process development and optimization of continuous capture with three‐column periodic counter‐current chromatography

Shi

Zhang

Jiao

et al. 2021

Biotech & Bioengineering

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Continuous capture with affinity chromatography is one of the most important units for continuous manufacturing of monoclonal antibody (mAb). Due to the complexity of three‐column periodic counter‐current chromatography (3C‐PCC), three approaches (experimental, model‐based, and simplified approaches) were studied for process development and optimization. The effects of residence time for interconnected load (RT C), breakthrough percentage of the first column for interconnected load (s) and feed protein concentration (c 0) on productivity and capacity utilization were focused. The model‐based approach was found superior to the experimental approach in process optimization and evaluation. Two phases of productivity were observed and the optimal RT C for the maximum productivity was located at the boundary of the two phases. The comprehensive effects of the operating parameters (RT C, s, and c 0) were evaluated by the model‐based approach, and the operation space was predicted. The best performance of 34.5 g/L/h productivity and 97.6% capacity utilization were attained for MabSelect SuRe LX resin under 5 g/L concentration at RT C = 2.8 min and s = 87.5%. Moreover, a simplified approach was suggested to obtain the optimal RT C for the maximum productivity. The results demonstrated that model‐assisted tools are useful to determine the optimum conditions for 3C‐PCC continuous capture with high productivity and capacity utilization.

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Optimization study on periodic counter-current chromatography integrated in a monoclonal antibody downstream process

Cited by 42 publications

References 24 publications

An integrated continuous downstream process with real‐time control: A case study with periodic countercurrent chromatography and continuous virus inactivation

An integrated continuous downstream process with real‐time control: A case study with periodic countercurrent chromatography and continuous virus inactivation

Analytical, Preparative, and Industrial-Scale Separation of Substances by Methods of Countercurrent Liquid-Liquid Chromatography

Process development and optimization of continuous capture with three‐column periodic counter‐current chromatography

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