Integrated flow-through purification for therapeutic monoclonal antibodies processing

Ichihara, Takamitsu; Ito, Takao; Kurisu, Yasuhiko; Galipeau, Kevin; Gillespie, Christopher

doi:10.1080/19420862.2017.1417717

Cited by 49 publications

(43 citation statements)

References 35 publications

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“…In contrast, our process provided continuous, uninterrupted mass flow, and a fully continuous process could be maintained. Furthermore, the outflow of the resolubilization reactor could be fed directly into a continuous virus inactivation solution, (Klutz, Lobedann, Bramsiepe, & Schembecker, ) and subsequent flow‐through chromatography (Ichihara, Ito, Kurisu, Galipeau, & Gillespie, ) would not interrupt the mass flow.…”

Section: Resultsmentioning

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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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: Resultsmentioning

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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“…All materials used in this study were the same as the previous feasibility study [11]. AC powder used in Millistak+ R CR40 devices was obtained from Merck KGaA (Darmstadt, Germany), HiTrap R Capto TM Q (AEX, cat#: 11-0013-02) was obtained from GE Healthcare (Buckinghamshire, UK) and Eshmuno R CP-FT resin provided by Merck KGaA (Darmstadt, Germany) was used for CEX.…”

Section: Methodsmentioning

confidence: 99%

“…The polishing steps of the purification process had been previously optimized by DOE study [11]. The polishing steps of the purification process had been previously optimized by DOE study [11].…”

Section: Connected Flow-through Chromatographymentioning

confidence: 99%

“…The feasibility of an all flow-through polishing process without buffer adjustment was studied [11]. The feasibility of an all flow-through polishing process without buffer adjustment was studied [11].…”

Section: Introductionmentioning

confidence: 99%

“…We recently tested a novel antibody purification process that offers significant operational advantages to traditional approaches. The feasibility of an all flow-through polishing process without buffer adjustment was studied [11]. This process template enables the possibility of pool-less processing with a single feed pump skid by utilizing optimum operating windows based on performance characteristics.…”

Section: Introductionmentioning

confidence: 99%

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Polishing approach with fully connected flow‐through purification for therapeutic monoclonal antibody

Ichihara

Ito

Gillespie³

2018

Engineering in Life Sciences

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The biopharmaceutical industry is evolving toward process intensification that can offer increased productivity and improved economics without sacrificing process robustness. A semi‐continuous downstream process linking purification/polishing unit operations in series can reduce or eliminate intermediate holding tanks and reduce overall processing time. Accordingly, we have developed a therapeutic monoclonal antibody polishing template comprised of a connected flow‐through polishing technologies that include activated carbon, cation exchange, and anion‐exchange chromatography. In this report, we evaluated fully‐connected pool‐less polishing with three flow‐through technologies, operating as a single skid to streamline and improve an mAb purification platform. Laboratory‐scale pool‐less processing was achieved without utilizing in‐line pH adjustment and conductivity dilution based on the previously optimized single process parameter. Two connected flow‐through configurations of polishing steps were evaluated: a two‐step process using anion exchange and cation exchange and a three step process using activated carbon, anion exchange and cation exchange chromatography. Laboratory‐scale proof of concept studies showed comparable performance between the batch purification process and the pool‐less process configuration. Three step polishing highly intensified the processes and provided higher process loading and achieved bulk drug specification with higher impurity clearance (>95%) and high overall mAb yield (>95%).

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Process Development of Protein Therapeutics

Huang¹,

Bowes²,

Yang³

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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The application of recombinant DNA technology to the production of protein therapeutics has undergone tremendous progress over the past decades. Considerable scientific effort has been devoted to developing robust processes that produce large amounts of complex proteins with the desired product quality attributes. An overview of the contributions from the four major disciplines working in concert to deliver these processes and methods will be covered. This article will discuss some of the tools, methods, and approaches used to produce, purify, formulate, and analyze the drugs of modern biotechnology. Future trends in each of the disciplines will also be presented.

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Integrated flow-through purification for therapeutic monoclonal antibodies processing

Cited by 49 publications

References 35 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

Polishing approach with fully connected flow‐through purification for therapeutic monoclonal antibody

Process Development of Protein Therapeutics

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