End-to-end integrated fully continuous production of recombinant monoclonal antibodies

Godawat, Rahul; Konstantinov, Konstantin; Rohani, Mahsa M.; Warikoo, Veena

doi:10.1016/j.jbiotec.2015.06.393

Cited by 199 publications

(152 citation statements)

References 26 publications

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“…(Dong et al, 2016;Godawat, Konstantinov, Rohani, & Warikoo, 2015), harvest costs will likely decrease further in the future. (Dong et al, 2016;Godawat, Konstantinov, Rohani, & Warikoo, 2015), harvest costs will likely decrease further in the future.…”

Section: Harvest Costs Dominate Cog But Can Be Reduced At Large Lotmentioning

confidence: 99%

Bioprocess decision support tool for scalable manufacture of extracellular vesicles

Smith

McAteer

et al. 2018

Biotech & Bioengineering

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Newly recognized as natural nanocarriers that deliver biological information between cells, extracellular vesicles (EVs), including exosomes and microvesicles, provide unprecedented therapeutic opportunities. Large-scale and cost-effective manufacturing is imperative for EV products to meet commercial and clinical demands; successful translation requires careful decisions that minimize financial and technological risks. Here, we develop a decision support tool (DST) that computes the most cost-effective technologies for manufacturing EVs at different scales, by examining the costs of goods associated with using published protocols. The DST identifies costs of labor and consumables during EV harvest as key cost drivers, substantiating a need for larger-scale, higher-throughput, and automated technologies for harvesting EVs. Importantly, we highlight a lack of appropriate technologies for meeting clinical demands, and propose a potentially cost-effective solution. This DST can facilitate decision-making very early on in development and be used to predict, and better manage, the risk of process changes when commercializing EV products.

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Section: Harvest Costs Dominate Cog But Can Be Reduced At Large Lotmentioning

confidence: 99%

Bioprocess decision support tool for scalable manufacture of extracellular vesicles

Smith

McAteer

et al. 2018

Biotech & Bioengineering

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Section: Continuous Desalting Of Refolded Protein Solution Improves Cmentioning

confidence: 99%

“…Not only FDA has addressed this topic [12,13], it also raised the interest of numerous researchers in both academia and industry [14,15]. Even it is not realized on a large production scale yet, various different strategies for continuous biomanufacturing have been developed in recent years [8,[16][17][18][19][20][21].In this work, we describe a novel alternative desalting process using microporous ion exchange resins, which are typically employed for water demineralization and are relatively inexpensive [22]. In the current work, this type of resin is referred to as "micropore resin" due to its small pore sizes of approximately 1-1.5 nm according to manufacturer information.…”

mentioning

confidence: 99%

Continuous desalting of refolded protein solution improves capturing in ion exchange chromatography: A seamless process

Walch

Jungbauer

2017

Biotechnology Journal

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Truly continuous biomanufacturing processes enable an uninterrupted feed stream throughout the whole production without the need for holding tanks. We have utilized microporous anion and cation exchangers into which only salts, but not proteins, can penetrate into the pores for desalting of protein solutions, while diafiltration or dilution is usually employed for feed adjustments. Anion exchange and cation exchange chromatography columns were connected in series to remove both anions and cations. To increase operation performance, a continuous process was developed comprised of four columns. Continuous mode was achieved by staggered cycle operation, where one set of columns, consisting of one anion exchange and one cation exchange column, was loaded during the regeneration of the second set. Refolding, desalting and subsequent ion exchange capturing with a scFv as the model protein was demonstrated. The refolding solution was successfully desalted resulting in a consistent conductivity below 0.5 mS/cm from initial values of 10 to 11 mS/cm. With continuous operation process time could be reduced by 39% while productivity was increased to 163% compared to batch operation. Desalting of the protein solution resulted in up to seven-fold higher binding capacities in the subsequent ion exchange capture step with conventional protein binding resins. www.biotechnology-journal.com Biotechnology Journalwww.advancedsciencenews.com Biotechnol. J. 2017, 12, 1700082 for IB resolubilization to unfold the protein followed by a dilution step to reduce the chaotropic conditions which initiates protein folding. However, such refolding buffers commonly require also elevated salt concentrations [5] which therefore results in feed streams being high in conductivity, making ion exchange chromatography an unsuitable option for the next unit operation. Ion exchange chromatography is attractive for industry due to the costefficient resins with high capacities. Hence, additional process steps such as dilution or diafiltration have to be introduced to reduce salt concentration in the solution and allow efficient binding of the protein to the ion exchange resins [6]. Despite the high potential of continuous downstream processing, it is still rarely applied in the manufacturing of biologics. Other industries such as the food and chemical sector, have already successfully implemented integrated processes which create highly flexible and efficient production [6,7]. In continuous operation equipment size can be down scaled, which reduces not only investment costs but also operating costs due to buffer savings [8,9]. Additionally optimized cycle times improve also productivity [10,11]. Not only FDA has addressed this topic [12,13], it also raised the interest of numerous researchers in both academia and industry [14,15]. Even it is not realized on a large production scale yet, various different strategies for continuous biomanufacturing have been developed in recent years [8,[16][17][18][19][20][21].In this work, we describe a novel alternati...

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“…Continuous biomanufacturing is actively being investigated in the therapeutic protein manufacturing space with a potential end-to-end continuous manufacturing vision [e.g. [13][14][15]. For viral vector manufacture for cell and gene therapies, continuous biomanufacture is being explored on the upstream front, with perfusion culture in fixed bed bioreactors [16] or stirred tank bioreactors, as well as the downstream front with continuous chromatography [17].…”

Section: Industry 40 In the Biopharmaceutical Industrymentioning

confidence: 99%

Industry 4.0: a vision for personalized medicine supply chains?

Branke¹,

Farid²,

Shah³

2016

Cell and Gene Therapy Insights

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Industry 4.0 foresees a digital transformation of manufacturing resulting in smart factories and supply chains. At the heart of the concept lies the vision of interconnected materials, goods and machines, where goods find their way through the factory and the supply chain to the customer in a self-organised manner. Industry 4.0 is gaining traction in high value manufacturing sectors. This perspective paper explores what this technology-driven vision has to offer for the biopharmaceutical industry, and in particular cell and gene therapies.

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End-to-end integrated fully continuous production of recombinant monoclonal antibodies

Cited by 199 publications

References 26 publications

Bioprocess decision support tool for scalable manufacture of extracellular vesicles

Bioprocess decision support tool for scalable manufacture of extracellular vesicles

Continuous desalting of refolded protein solution improves capturing in ion exchange chromatography: A seamless process

Industry 4.0: a vision for personalized medicine supply chains?

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