Scale-up of continuous multicolumn chromatography for the protein a capture step: From bench to clinical manufacturing

Ötes, Ozan; Flato, Hendrik; Ramirez, Daniel Vazquez; Badertscher, Britta; Bisschops, Marc; Capito, Florian

doi:10.1016/j.jbiotec.2018.07.022

Cited by 25 publications

(7 citation statements)

References 17 publications

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“…Continuous processes have been employed in pharmaceutical industries as the need for high throughput downstream processes has increased [133]. Continuous chromatography has been developed for the purification of antibodies [57,134] and more recently, for different particles such as adenovirus [135][136][137], influenza [138,139] and extracellular vesicles [84]. Periodic countercurrent chromatography (PCC) and countercurrent simulated moving bed (SMB) are the most advanced systems used in biopharmaceutical industry [138,140].…”

Section: Innovations In Purification Technologiesmentioning

confidence: 99%

Current challenges in biotherapeutic particles manufacturing

Moleirinho

Silva

Alves

et al. 2019

Expert Opinion on Biological Therapy

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Introduction: The development of novel complex biotherapeutics led to new challenges in biopharmaceutical industry. The potential of these particles has been demonstrated by the approval of several products, in the different fields of gene therapy, oncolytic therapy, and tumor vaccines. However, their manufacturing still presents challenges related to the high dosages and purity required. Areas covered: The main challenges that biopharmaceutical industry faces today and the most recent developments in the manufacturing of different biotherapeutic particles are reported here. Several unit operations and downstream trains to purify virus, virus-like particles and extracellular vesicles are described. Innovations on the different purification steps are also highlighted with an eye on the implementation of continuous and integrated processes. Expert opinion: Manufacturing platforms that consist of a low number of unit operations, with higheryielding processes and reduced costs will be highly appreciated by the industry. The pipeline of complex therapeutic particles is expanding and there is a clear need for advanced tools and manufacturing capacity. The use of single-use technologies, as well as continuous integrated operations, are gaining ground in the biopharmaceutical industry and should be supported by more accurate and faster analytical methods.

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Section: Innovations In Purification Technologiesmentioning

confidence: 99%

Current challenges in biotherapeutic particles manufacturing

Moleirinho

Silva

Alves

et al. 2019

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

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“…The continuous downstream processing of extracellular proteins derived from cell culture cultivations (mostly monoclonal antibody production) is already implemented in some branches of the pharmaceutical industry (Vogel et al, 2012; Ötes et al, 2018). Proteins can be separated from impurities at high efficiency either with SMB (simulated moving bed)-chromatography or continuous membrane chromatography (Shekhawat and Rathore, 2019).…”

Section: The Continuous Downstream Processing Of Intracellular Proteinsmentioning

confidence: 99%

“…Fusing purification steps into an overall non-stop process seemed unlikely to be achieved a couple of years ago (Rathore, 2015; Vemula et al, 2015; Kante et al, 2018, 2019; VKR et al, 2019). Continuous chromatography in particular created a bottleneck; however, simulated moving bed chromatography (SMBC) improved significantly in terms of performance (Ötes et al, 2017, 2018). With state of the art technology, we are able to process proteins independent of location and at a continuous level (Jungbauer, 2013; Saraswat et al, 2013; Wellhoefer et al, 2013, 2014), and we are able to unite all process unit operations into one overall process (Lee et al, 2015; Zydney, 2015; Burcham et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The Rocky Road From Fed-Batch to Continuous Processing With E. coli

Kopp

Slouka²,

Spadiut³

et al. 2019

Front. Bioeng. Biotechnol.

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Escherichia coli still serves as a beloved workhorse for the production of many biopharmaceuticals as it fulfills essential criteria, such as having fast doubling times, exhibiting a low risk of contamination, and being easy to upscale. Most industrial processes in E. coli are carried out in fed-batch mode. However, recent trends show that the biotech industry is moving toward time-independent processing, trying to improve the space–time yield, and especially targeting constant quality attributes. In the 1950s, the term “chemostat” was introduced for the first time by Novick and Szilard, who followed up on the previous work performed by Monod. Chemostat processing resulted in a major hype 10 years after its official introduction. However, enthusiasm decreased as experiments suffered from genetic instabilities and physiology issues. Major improvements in strain engineering and the usage of tunable promotor systems facilitated chemostat processes. In addition, critical process parameters have been identified, and the effects they have on diverse quality attributes are understood in much more depth, thereby easing process control. By pooling the knowledge gained throughout the recent years, new applications, such as parallelization, cascade processing, and population controls, are applied nowadays. However, to control the highly heterogeneous cultivation broth to achieve stable productivity throughout long-term cultivations is still tricky. Within this review, we discuss the current state of E. coli fed-batch process understanding and its tech transfer potential within continuous processing. Furthermore, the achievements in the continuous upstream applications of E. coli and the continuous downstream processing of intracellular proteins will be discussed.

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“…In many cases, due to delays in analysis, supporting analytical data are used only for batch records or as a future reference. With the implementation of continuous manufacturing practices in the pharmaceutical industry in the near future, the ability to provide analytical data to the production team in a short time, if not in real‐time, will take on increased importance [ 7 , 8 , 9 , 10 , 11 , 12 ]. A quick and simple testing method that can be easily performed in the proximity of the production floor would ensure timely corrective action when, for instance, a sudden spike of mannose is detected after the addition of various cell culture feed ingredients in the manufacturing process for therapeutic mAbs.…”

Section: Introductionmentioning

confidence: 99%

Rapid monitoring of high‐mannose glycans during cell culture process of therapeutic monoclonal antibodies using lectin affinity chromatography

Kim

Albarghouthi

2022

J of Separation Science

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We developed a simple high-performance liquid chromatography assay to monitor high-mannose glycans in monoclonal antibodies by monitoring terminal alpha-mannose as a surrogate marker. Analysis of glycan data of therapeutic monoclonal antibodies by 2-aminobenzamide assay showed a linear relationship between high mannose and terminal mannose of Fc glycans. Concanavalin A has a strong affinity to alpha-mannose in glycans of typical therapeutic monoclonal antibodies. To show that terminal mannose binds specifically to Concanavalin A column, exoglycosidase-treated monoclonal antibodies were serially blended with untreated monoclonal antibodies. Linear responses of terminal-mannose binding to the column and comparable data trending with high mannose levels by 2-aminobenzamide assay confirmed that terminal-mannose levels measured by the Concanavalin A column can be used as a surrogate for the prediction of high-mannose levels in monoclonal antibodies. The assay offers a simple, fast, and specific capability for the prediction of high-mannose content in samples compared with traditional glycan profiling by 2-aminobenzamide or mass spectrometry-based methods. When the Concanavalin A column was coupled with protein A column for purification of antibodies from cell culture samples in a fully automated two-dimensional analysis, high-mannose data could be relayed to the manufacturing team in less than 30 min, allowing near-real-time monitoring of high-mannose levels in the cell culture process.

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Scale-up of continuous multicolumn chromatography for the protein a capture step: From bench to clinical manufacturing

Cited by 25 publications

References 17 publications

Current challenges in biotherapeutic particles manufacturing

Current challenges in biotherapeutic particles manufacturing

The Rocky Road From Fed-Batch to Continuous Processing With E. coli

Rapid monitoring of high‐mannose glycans during cell culture process of therapeutic monoclonal antibodies using lectin affinity chromatography

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