Single pass diafiltration integrated into a fully continuous mAb purification process

Rucker-Pezzini, Joanna; Arnold, Lindsay; Hill-Byrne, Kevin; Sharp, Tom; Avazhanskiy, Maksim; Forespring, Chris

doi:10.1002/bit.26708

Cited by 43 publications

(21 citation statements)

References 15 publications

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“…The process described here had several advantages over other methods. First, it incorporates a simple, robust setup of readily available instrumentation, because TFF is a standard unit operation currently used in the pharmaceutical industry for buffer exchanges, perfusion systems, and other operations (Rucker-Pezzini et al, 2018).…”

Section: Continuous Diafiltrationmentioning

confidence: 99%

“…However, that strategy interrupts the fully continuous operation, and the antibody must be harvested in cycles. Another possibility is single-pass tangential flow filtration (TFF), which allows the solid to be harvested in a single pass through a cascade of membrane filters (Casey, Gallos, Alekseev, Ayturk, & Pearl, 2011;Rucker-Pezzini et al, 2018). The third choice is countercurrent TFF.…”

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confidence: 99%

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Continuous integrated antibody precipitation with two‐stage tangential flow microfiltration enables constant mass flow

Burgstaller

Jungbauer

Satzer

2019

Biotech & Bioengineering

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Continuous precipitation is a new unit operation for the continuous capture of antibodies. The capture step is based on continuous precipitation with PEG6000 and Zn ++ in a tubular reactor integrated with a two‐stage continuous tangential flow filtration unit. The precipitate cannot be separated with centrifugation, because a highly compressed sediment results in poor resolubilization. We developed a new two‐stage tangential flow microfiltration method, where part of the concentrated retentate of the first stage was directly fed to the second stage, together with the wash buffer. Thus, the precipitate was concentrated and washed in a continuous process. We obtained 97% antibody purity, a 95% process yield during continuous operation, and a fivefold reduction in pre‐existing high‐molecular‐weight impurities. For other unit operations, surge tanks are often required, due to interruptions in the product mass flow out of the unit operation (e.g., the bind/elute mode in periodic counter‐current chromatography). Our setup required no surge tanks; thus, it provided a truly continuous antibody capture operation with uninterrupted product mass flow. Continuous virus inactivation and other flow‐through unit operations can be readily integrated downstream of the capture step to create truly continuous, integrated, downstream antibody processing without the need for hold tanks.

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Section: Continuous Diafiltrationmentioning

confidence: 99%

mentioning

confidence: 99%

Continuous integrated antibody precipitation with two‐stage tangential flow microfiltration enables constant mass flow

Burgstaller

Jungbauer

Satzer

2019

Biotech & Bioengineering

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“…The last step in the drug substance (API) biopharmaceutical manufacturing is the formulation step, which includes buffer exchange and protein concentration. Instead of traditional ultrafiltration and diafiltration processes, single-pass tangential flow filtration (SPTFF) [52], cascade diafiltration, counter current staged diafiltration [53], and crystallization can also be used to achieve continuous protein production [9,28]. Rucker-Pezzini et al [52] integrated SPTFF with other continuous upstream and downstream unit operations and built an end to end continuous process operation.…”

Section: Economic Analyses 21 Biologics Operationsmentioning

confidence: 99%

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

Qadan

Ierapetritou

2019

J Pharm Innov

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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.

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“…Additionally, the multistep setup offers the possibility to vary the properties of the membranes by adjustment to the conditions of the protein solution. Diafiltration systems are also possible in this multistep setup by adding in between the filtration stages [36]. Despite the more complex setup with additional pumps, the SPTFF diafiltration provides many advantages like reduced buffer volume and less shear stress due to pumping of the target molecule [37].…”

Section: Introductionmentioning

confidence: 99%

Model-Based Design and Process Optimization of Continuous Single Pass Tangential Flow Filtration Focusing on Continuous Bioprocessing

Huter

Strube

2019

Processes

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In this study the Single-Pass-Tangential-Flow-Filtration (SPTFF) concept for continuous ultrafiltration in bioprocessing is investigated. Based on a previously validated physico-chemical model for a single ultrafiltration cassette, the transfer to a multistage SPTFF is predicted and validated experimentally by concentration steps for bovine serum albumin (BSA) and the monoclonal antibody immunoglobulin G (IgG) are compared. The model applied for the ultrafiltration membrane contains the Stagnant Film Model (SFM) for concentration polarization, as well as the Osmotic Pressure Model (OPM) and the Boundary Layer Model (BLM) for the mass transfer through the membrane. In addition, pressure drop correlations as a function of the Reynolds number are included to describe the development of the transmembrane pressure over the length of the module. The outcome of this study shows the potential to improve this multi-parameter dependent unit operation by a model-based optimization allowing significant reduction of experimental efforts and applying the Quality by Design (QbD) approach consistently. Consequently, a versatile tool for conceptual process design is presented and further application is discussed.

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Single pass diafiltration integrated into a fully continuous mAb purification process

Cited by 43 publications

References 15 publications

Continuous integrated antibody precipitation with two‐stage tangential flow microfiltration enables constant mass flow

Continuous integrated antibody precipitation with two‐stage tangential flow microfiltration enables constant mass flow

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

Model-Based Design and Process Optimization of Continuous Single Pass Tangential Flow Filtration Focusing on Continuous Bioprocessing

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