Viral clearance in end‐to‐end integrated continuous process for mAb purification: Total flow‐through integrated polishing on two columns connected to virus filtration

Shirataki, Hironobu; Matsumoto, Yoshihiro; Konoike, Fuminori; Yamamoto, Shuichi

doi:10.1002/bit.28464

Cited by 4 publications

(3 citation statements)

References 29 publications

(45 reference statements)

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“…The detailed analysis of the two-connected FTC column operation with VF attached to the 2nd column including viral clearance studies has been reported in Shirataki et al (2023).…”

Section: Polish Stepmentioning

confidence: 99%

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Integrated continuous downstream process of monoclonal antibody developed by converting the batch platform process based on the process characterization

Konoike,

Taniguchi,

Yamamoto

2023

Biotech & Bioengineering

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A continuous downstream process of monoclonal antibody was developed based on the process characterization. Periodic‐counter current chromatography (PCCC) with two protein A columns was used for the capture step. For low pH virus inactivation (VI), a batch reactor was employed, which can work as a surge (buffer) tank. Flow‐through chromatography (FTC) with two connected columns of different separation modes (anion‐mixed mode and cation exchange) was designed as a polish step. After 24 h PCCC run, the collected pool was processed for VI. After adjusting pH and electric conductivity, the solution was fed to the two connected FTC columns for 24 h. Virus filter was also connected to the exit of the connected‐column. PCCC and FTC were run in parallel. Six runs of different feed rates (0.5–10 L/day) and feed concentrations (1–3.2 g/L) were performed with protein A columns of 1–5 mL and FTC columns of 3–10 mL. The largest run (feed rate 10 L/day, feed concentration 2 g/L) was carried out at a GMP facility with 15 mL protein A columns and 100 mL FTC columns. Good recovery and purity values were obtained for all runs. The process was found to be flexible and stable for feed fluctuations. Only three surge or pool tanks were needed in addition to the final product pool tank.

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“…The detailed analysis of the two-connected FTC column operation with VF attached to the 2nd column including viral clearance studies has been reported in Shirataki et al (2023).…”

Section: Polish Stepmentioning

confidence: 99%

“…was lower due to the misoperations (some of the pool was lost). The detailed analysis on Run 4 was published in Shirataki et al (2023).…”

Section: Icdspmentioning

confidence: 99%

Integrated continuous downstream process of monoclonal antibody developed by converting the batch platform process based on the process characterization

Konoike,

Taniguchi,

Yamamoto

2023

Biotech & Bioengineering

Self Cite

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“…The choice of appropriate buffers used in cyclic operations of different chromatography unit operations is based on the literature. Additionally, filtrate flux in tangential flow filtration unit operations applied for diafiltration or concentrating protein solution is selected based on manufacturing instructions [52]. Finally, the operating conditions in the PEGylation reactor (i.e., reaction buffer's pH and temperature), the kinetic parameters constants used to evaluate the time to achieve a specific yield of PEG-AAT, and the operating conditions of chromatography unit operation to separate PEG-AAT from AAT were extracted from the literature [44,53].…”

Section: Introductionmentioning

confidence: 99%

Technoeconomic Analysis of Intensified PEGylated Biopharmaceutical Recombinant Protein Production: Alpha Antitrypsin as a Model Case

Alkanaimsh,

Alsalal,

El-Touney

2024

Processes

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Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by the insufficient production of the AAT protein. Due to availability limitations, not all AATD patients receive protein therapy treatment. In this study, the technoeconomic analysis of different processes (conventional and intensified) producing 200 kg/year of PEGylated recombinant AAT (PEG-AAT) using a Chinese hamster ovary cell line was investigated. All bioprocesses consist of upstream, downstream, and PEGylation sections. A base-case model (process A) of the conventional fed-batch production bioreactor was developed using SuperPro Designer software (Version 13) to evaluate the economic feasibility of the process. The cost of goods (COG) was estimated to be approximately USD 387.6/g. Furthermore, an intensified process (B) was modeled and evaluated to reduce the COG. Process intensification was implemented in the process (N-1 perfusion bioreactor). The specific operating COG for process B was found to be 10% less than that of process A. Scenario analysis was performed to assess the impact of process capacity (100–1000 kg/year) and cell-specific productivity (30–90 pg/cell/day). With an increase in process capacity, the specific operating COG was reduced for all processes. Increasing cell-specific productivity decreases the specific operating COG at different rates for each process, depending on the titer level. Future investigations into the PEGylation section are required since it has the highest COG of all the sections.

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Residence time distribution in continuous virus filtration

Chen,

Recanati,

De Mathia

et al. 2024

Biotech & Bioengineering

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Regulatory authorities recommend using residence time distribution (RTD) to address material traceability in continuous manufacturing. Continuous virus filtration is an essential but poorly understood step in biologics manufacturing in respect to fluid dynamics and scale‐up. Here we describe a model that considers nonideal mixing and film resistance for RTD prediction in continuous virus filtration, and its experimental validation using the inert tracer NaNO3. The model was successfully calibrated through pulse injection experiments, yielding good agreement between model prediction and experiment ( 0.90). The model enabled the prediction of RTD with variations—for example, in injection volumes, flow rates, tracer concentrations, and filter surface areas—and was validated using stepwise experiments and combined stepwise and pulse injection experiments. All validation experiments achieved 0.97. Notably, if the process includes a porous material—such as a porous chromatography material, ultrafilter, or virus filter—it must be considered whether the molecule size affects the RTD, as tracers with different sizes may penetrate the pore space differently. Calibration of the model with NaNO3 enabled extrapolation to RTD of recombinant antibodies, which will promote significant savings in antibody consumption. This RTD model is ready for further application in end‐to‐end integrated continuous downstream processes, such as addressing material traceability during continuous virus filtration processes.

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Viral clearance in end‐to‐end integrated continuous process for mAb purification: Total flow‐through integrated polishing on two columns connected to virus filtration

Cited by 4 publications

References 29 publications

Integrated continuous downstream process of monoclonal antibody developed by converting the batch platform process based on the process characterization

Integrated continuous downstream process of monoclonal antibody developed by converting the batch platform process based on the process characterization

Technoeconomic Analysis of Intensified PEGylated Biopharmaceutical Recombinant Protein Production: Alpha Antitrypsin as a Model Case

Residence time distribution in continuous virus filtration

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