Multistage continuous countercurrent diafiltration for formulation of monoclonal antibodies

Jabra, Mario G.; Yehl, Christopher J.; Zydney, Andrew L.

doi:10.1002/btpr.2810

Cited by 32 publications

(29 citation statements)

References 9 publications

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“…Although traditional diafiltration can provide high degrees of impurity removal in batch processes, this approach is not readily extendable to continuous processing, which is increasingly attractive for large‐scale biomanufacturing 15 . Instead, a countercurrent staged membrane process can be used to achieve the desired degree of washing 16,17 . The extent of impurity removal ( R ) in this type of multistage countercurrent membrane process is given as 18 :

R = \frac{C_{feed}}{C} = \frac{α^{N + 1} - 1}{α - 1},

with

α = \frac{Q_{wash}}{Q_{feed}} = \frac{x}{1 - x},

where C feed is the concentration of soluble impurities in the feed entering the wash step, C is the concentration of soluble impurities leaving the wash step, Q feed is the feed flow rate, Q wash is the flow rate of the wash buffer, N is the number of stages, and x is the conversion in the membrane module (equal to the ratio of the permeate flow rate to inlet feed flow rate for the membrane module).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced filtration performance usingfeed‐and‐bleedconfiguration for purification of antibody precipitates

Zhao

Chen

Andini

et al. 2020

Biotechnology Progress

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Precipitation can be used for the initial purification of monoclonal antibodies (mAbs), with the soluble host cell proteins removed in the permeate by tangential flow microfiltration. The objective of this study was to examine the use of a feed-andbleed configuration to increase the effective conversion (ratio of permeate to feed flow rates) in the hollow fiber module to enable more effective washing of the precipitate. Experiments were performed using human serum Immunoglobulin G (IgG) precipitates formed with 10 mM zinc chloride and 7 wt% polyethylene glycol. The critical flux was evaluated as a function of the shear rate and IgG concentration, with the resulting correlation used to predict conditions that can achieve 90% conversion in a single pass with minimal fouling. Experimental data for both the start-up and steady-state performance are in good agreement with model calculations. These results were used to analyze the performance of an enhanced continuous precipitation-microfiltration process using the feed-and-bleed configuration for the initial capture / purification of a mAb product.

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R = \frac{C_{feed}}{C} = \frac{α^{N + 1} - 1}{α - 1},

with

α = \frac{Q_{wash}}{Q_{feed}} = \frac{x}{1 - x},

Section: Introductionmentioning

confidence: 99%

“…15 Instead, a countercurrent staged membrane process can be used to achieve the desired degree of washing. 16,17 The extent of impurity removal (R) in this type of multistage countercurrent membrane process is given as 18 :…”

mentioning

confidence: 99%

Enhanced filtration performance usingfeed‐and‐bleedconfiguration for purification of antibody precipitates

Zhao

Chen

Andini

et al. 2020

Biotechnology Progress

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“…A countercurrent staged diafiltration process was performed for continuous protein formulation for a polyclonal IgG with Cadence TM Inline concentrators (Nambiar et al, 2017). Cadence TM in-line concentrators (Delta 30 kDa membranes) were used in the three stages to obtain high conversion in a single pass and provided important insights into the design and operation of a continuous process for antibody formulation (Jabra et al, 2019). Countercurrent dialysis for continuous protein formulation and buffer exchange was done using concentrated solutions of IgG with commercially available hollow fiber dialyzers (1.5 and 1.8 m 2 membrane surface area) (Yehl et al, 2019).…”

Section: Continuous Formulationmentioning

confidence: 99%

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

Tripathi

Shrivastava

2019

Front. Bioeng. Biotechnol.

402

243

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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.

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“…The product then passes through an in‐line diafiltration (ILDF) step made up of several stages of dilution and SPTFF modules. These modules are most efficient when operated in a counter‐current mode (Arnold et al, 2019; Huter & Strube, 2019; Jabra et al, 2019; Nambiar et al, 2018; Rucker‐Pezzini et al, 2018). The final drug substance concentration is achieved through a final SPTFF step.…”

Section: The Common Framework For Integrated and Continuous Manufactumentioning

confidence: 99%

A common framework for integrated and continuous biomanufacturing

Coffman¹,

Brower

Connell-Crowley

et al. 2021

Biotech & Bioengineering

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There is a growing application of integrated and continuous bioprocessing (ICB) for manufacturing recombinant protein therapeutics produced from mammalian cells. At first glance, the newly evolved ICB has created a vast diversity of platforms. A closer inspection reveals convergent evolution: nearly all of the major ICB methods have a common framework that could allow manufacturing across a global ecosystem of manufacturers using simple, yet effective, equipment designs. The framework is capable of supporting the manufacturing of most major biopharmaceutical ICB and legacy processes without major changes in the regulatory license. This article reviews the ICB that are being used, or are soon to be used, in a GMP manufacturing setting for recombinant protein production from mammalian cells. The adaptation of the various ICB modes to the common ICB framework will be discussed, along with the pros and cons of such adaptation. The equipment used in the common framework is generally described. This review is presented in sufficient detail to enable discussions of IBC implementation strategy in biopharmaceutical companies and contract manufacturers, and to provide a road map for vendors equipment design. An example plant built on the common framework will be discussed. The flexibility of the plant is demonstrated with batches as small as 0.5 kg or as large as 500 kg. The yearly output of the plant is as much as 8 tons.

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Multistage continuous countercurrent diafiltration for formulation of monoclonal antibodies

Cited by 32 publications

References 9 publications

Enhanced filtration performance usingfeed‐and‐bleedconfiguration for purification of antibody precipitates

Enhanced filtration performance usingfeed‐and‐bleedconfiguration for purification of antibody precipitates

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

A common framework for integrated and continuous biomanufacturing

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