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- Glycosylation (2)
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- 2000L SUBs (1)
- AEX capture purification. (1)
- Biopharmaceuticals (1)
- Bioprocessing (1)
- Biphasic perfusion (1)
- Cationic flocculants (1)
- Clarification (1)
- DoE. (1)
- EMA (1)
- Extreme cell densities (1)
- Flocculation (1)
Articles 1 - 30 of 32
Full-Text Articles in Engineering
Development And Large Scale Manufacturing Of Exosome-Based Therapeutics, Konstantin Konstantinov
Development And Large Scale Manufacturing Of Exosome-Based Therapeutics, Konstantin Konstantinov
Integrated Continuous Biomanufacturing III
No abstract provided.
Delivering A Toolbox Of Flexible Platforms For Clinical And Commercial Bioprocessing Production: ‘Defining The Business Drivers For Development And Implementation’, Mark Brower, David Pollard
Delivering A Toolbox Of Flexible Platforms For Clinical And Commercial Bioprocessing Production: ‘Defining The Business Drivers For Development And Implementation’, Mark Brower, David Pollard
Integrated Continuous Biomanufacturing III
Despite the growing success, the biopharmaceutical industry continues to face competitive challenges from multiple sources. The cost pressures include evolving reimbursement, global competition and loss of drug exclusivity. As a result, there is a significant drive to boost the overall productivity of bio therapeutic programs by shortening development timelines and lowering both development and production costs, while maintaining product quality. Low cost production solutions must be aggressively pursued due to the large number of drug candidates in development, and their relatively high dosing requirements. The industry is facing an expanding range of modalities such as bispecifics and nanobodies, that provide …
Continuous Manufacturing - Ema Perspective And Experience, Nino Mihokovic
Continuous Manufacturing - Ema Perspective And Experience, Nino Mihokovic
Integrated Continuous Biomanufacturing III
Continuous manufacturing provides a distinct set of advantages and challenges from technical and regulatory viewpoints. Challenges such as batch definition and traceability, dynamic control strategies, use of Process Analytical Technologies, validation strategies and specifications are some of the areas which can require new perspectives from both industry and regulators. This presentation will reflect on the current regulatory environment and principles applied to continuous manufacturing; it aims to share the European experience with marketing authorisation applications using aspects of continuous manufacturing; and outlines Agency support to innovation and opportunities to consult and interact with the regulatory authorities during various stages of …
Continuous Freeze-Drying And Its Relevance To The Pharma/Biotech Industry, Roberto Pisano, Luigi C. Capozzi, Bernhardt Trout
Continuous Freeze-Drying And Its Relevance To The Pharma/Biotech Industry, Roberto Pisano, Luigi C. Capozzi, Bernhardt Trout
Integrated Continuous Biomanufacturing III
The new paradigm of pharmaceutical industry is to move from batch to continuous processes in order to satisfy the stringent requirements of quality, safety and efficiency set by regulatory authorities and reduce production costs. In this perspective, freeze-drying needs to be completely rethought in order to be more integrated in the chain of production of drugs, more flexible to respond to variations in market needs and allowing the monitoring of product quality. The future of freeze-drying, as a downstream process, is therefore to move from batch to continuous. Over the past decades many ideas regarding continuous freeze-drying has been proposed, …
Conversion Of An Industrial Batch Separation Process To An Autonomous Integrated Downstream Process – A Case Study Anton Lofgren, Lund University, Sweden, Anton Löfgren, Niklas Andersson, Joaquin Gomis Fons, Anton Sellberg, Bernt Nilsson
Conversion Of An Industrial Batch Separation Process To An Autonomous Integrated Downstream Process – A Case Study Anton Lofgren, Lund University, Sweden, Anton Löfgren, Niklas Andersson, Joaquin Gomis Fons, Anton Sellberg, Bernt Nilsson
Integrated Continuous Biomanufacturing III
In this contribution an industrial case study, consisting of several unit operations operated in batch mode, was converted to an integrated separation process. The complete downstream process consisted of an anion exchange step, followed by virus inactivation and finally a hydrophobic interaction step. Moving from batch to integrated separation minimizes hold-up times, storage tanks and required equipment. The conversion from batch to integrated mode was achieved by extracting operating points and separation data from batch chromatograms. The integrated separation process was realized on an ÄKTA Pure controlled by a newly developed software called Orbit. The setup consisted of two column …
Supervisory Control Of Integrated Continuous Downstream Processes, Bernt Nilsson, Niklas Andersson, Joaquin Gomis Fons, Anton Löfgren
Supervisory Control Of Integrated Continuous Downstream Processes, Bernt Nilsson, Niklas Andersson, Joaquin Gomis Fons, Anton Löfgren
Integrated Continuous Biomanufacturing III
Smart downstream processing can be performed with a sequence of integrated purification steps, which minimize the number of storage tanks and reduce hold-up time. The result is an integrated unit operation sequence that performs straight through processing of the target protein, with minimal time from expression to formulation. This downstream processing technique is well suited to be connected to a continuous upstream process based on perfusion. To develop these kinds of processes it is important to do studies in small-scale in a convenient way. This paper presents a methodology for supervisory control of integrated continuous downstream processes in lab-scale. A …
Ultra Scale-Down Mimics For Perfusion Culture: Experimental Study For Rapid Biopharmaceutical Process Development, Molly Tregidgo, David Pollard, Martina Micheletti
Ultra Scale-Down Mimics For Perfusion Culture: Experimental Study For Rapid Biopharmaceutical Process Development, Molly Tregidgo, David Pollard, Martina Micheletti
Integrated Continuous Biomanufacturing III
With the industry driving towards the implementation of whole continuous bioprocess sequences, there becomes a requirement for the development of scale-down tools with the same consistency, reliability and throughput as those already available for traditional batch processes. This work aims to develop a perfusion scale-down system capable of reproducing the specific characteristics of the perfusion culture process, namely cell retention capabilities, the ability to support high cell densities and to operate for extended periods compared to fed-batch cultures. Cell culture in microwell plates in fed-batch mode is well defined and is in widespread use; however to the best of our …
Fouling Mitigation In Membrane Based Perfusion Systems By Oscillating Tangential Flow, Maria Weinberger, Ulrich Kulozik
Fouling Mitigation In Membrane Based Perfusion Systems By Oscillating Tangential Flow, Maria Weinberger, Ulrich Kulozik
Integrated Continuous Biomanufacturing III
Good scalability and robust handling have promoted the application of membrane based cell retention devices. A physical barrier, i.e. a filter, retains cells and cell debris. One major drawback of these devices is their ten-dency to foul and clog. One form of fouling is deposit layer formation on the filter surface, consisting of cells, cell debris and other fermentation broth constituents. This leads to the build-up of a secondary membrane, which can alter the permeation profile. Furthermore, deposit layers lead to an increased filtration resistance and thus negatively affect permeate flux, filtration efficiency and process robustness. In tangential flow filtration, …
Scalable Technologies For Process Intensification In The Continuous Biomanufacturing Factories Of The Future, Gerben Zijlstra
Scalable Technologies For Process Intensification In The Continuous Biomanufacturing Factories Of The Future, Gerben Zijlstra
Integrated Continuous Biomanufacturing III
Continuous and intensified bioprocessing is attracting much attention from biopharmaceutical companies seeking to maximize the efficiency of their manufacturing assets. Continuous and intensified bioprocessing promises smaller facilities, reduced scale-up risk, more consistent product quality and higher throughputs. However, there are still many (technical) challenges for practical implementation of intensified and continuous bioprocesses. In the upstream processing, tools for high throughput intensified and continuous cell culture development are limited, furthermore at 2000 L scale many single use bioreactors may not be suitable to support the high cell densities required for intensified processing. Furthermore, current cell retention systems are expensive, suffer from …
Continuous Gas Processing Without Bubbles Using Thin Liquid Film Bioreactors Containing Biocomposite Biocatalysts, Michael C. Flickinger, Christopher Duran, Adam Wallace, Mark J. Schulte, Orlin D. Velev, Nilay Chakraborty, Michael Guarnieri, Kamelia Boodhoo
Continuous Gas Processing Without Bubbles Using Thin Liquid Film Bioreactors Containing Biocomposite Biocatalysts, Michael C. Flickinger, Christopher Duran, Adam Wallace, Mark J. Schulte, Orlin D. Velev, Nilay Chakraborty, Michael Guarnieri, Kamelia Boodhoo
Integrated Continuous Biomanufacturing III
Continuous microbial gas processing without bubbles is possible with thin liquid film, plug flow bioreactors. We have demonstrated that power input can be minimized by using a falling liquid film operating under laminar wavy flow conditions (Re <200) in contact with highly concentrated living, non-growing microbes stabilized in a porous biocomposite biocatalyst. This composite materials approach to continuous gas processing can dramatically increase mass transfer rates >100 fold compared to bubble aeration, decrease process volume, significantly decrease gas-liquid mass transfer energy input, decrease water use, and increase secreted product concentration. We have shown that this approach can also increase microbial specific activity for some organisms compared to microbes suspended in liquid media. Paper-based biocomposite biocatalysts provide a rough hydrophilic surface resulting in uniform ~300 μm thick falling liquid films. …
Bioprocess Intensification And Optimisation Using Macroscopic Predictive Models Of Cell Culture Processes, Bassem Ben Yahia, Boris Fessler, Gwendal Gränicher, An-Vy Tran, Mareike Harmsen, Elmar Heinzle
Bioprocess Intensification And Optimisation Using Macroscopic Predictive Models Of Cell Culture Processes, Bassem Ben Yahia, Boris Fessler, Gwendal Gränicher, An-Vy Tran, Mareike Harmsen, Elmar Heinzle
Integrated Continuous Biomanufacturing III
Chinese Ovary Hamster (CHO) are an indispensable tool for biotechnological production of biologics which is a multi-million business. Recently, the pharmaceutical industry is increasingly focusing in the use of perfusion mode. Nevertheless, the optimal perfusion rate during biopharmaceutical perfusion production is dependent on cell metabolism which can be characterized by mathematical models. This study provides insights into the predictive capacities of systematic and simple cell modeling approaches of metabolism, growth and production of monoclonal antibodies (mAb) [1] to optimized medium composition and perfusion rate during CHO perfusion culture. We applied the metabolic steady state concept and used a segmented linear …
Process Intensification: Enabling Technologies And Methodologies, Jonathan Souquet, Xavier Lesaout, Herve Broly
Process Intensification: Enabling Technologies And Methodologies, Jonathan Souquet, Xavier Lesaout, Herve Broly
Integrated Continuous Biomanufacturing III
The objective of this presentation is to review how emerging continuous manufacturing technology solutions can be leveraged to maximize existing facility utilization, throughput and capacity with particular focus on downstream process applications. Business and Market pressures driving the industry towards more efficient and effective manufacturing models will be reviewed. Downstream process bottlenecks and their impact on facility utilization and productivity will be addressed, and insight into enabling continuous manufacturing technologies and methodologies that can address these challenges will be provided. Case studies will be used to highlight the impact of applying continuous manufacturing principles on cost of supply, facility capacity …
Up And Down Scale Considerations For The Continuous Production Of Glycooptimized Biopharmaceuticals, Steffen Kreye, Rainer Stahn
Up And Down Scale Considerations For The Continuous Production Of Glycooptimized Biopharmaceuticals, Steffen Kreye, Rainer Stahn
Integrated Continuous Biomanufacturing III
Product quality especially with respect to glycosylation is a critical product attribute which can have an immense influence on the activity of glycoproteins and should be closely monitored during process development and manufacturing. GlycoExpressTM cells have been developed in this context to provide human host cell lines with robust glycosylation machineries. This work will address challenges in two case studies for up and down scaling of production processes with focus on product quality and continuous processing. In a first section, data of a process transfer from a 200 L stainless steel to a 1000 L single-use bioreactor for a continuous …
Conversion Of An Industrial Batch Separation Process To An Autonomous Integrated Downstream Process – A Case Study, Anton Lofgren, Niklas Andersson, Joaquin Gomis Fons, Anton Sellberg, Bernt Nilsson
Conversion Of An Industrial Batch Separation Process To An Autonomous Integrated Downstream Process – A Case Study, Anton Lofgren, Niklas Andersson, Joaquin Gomis Fons, Anton Sellberg, Bernt Nilsson
Integrated Continuous Biomanufacturing III
In this contribution an industrial case study, consisting of several unit operations operated in batch mode, was converted to an integrated separation process. The complete downstream process consisted of an anion exchange step, followed by virus inactivation and finally a hydrophobic interaction step. Moving from batch to integrated separation minimizes hold-up times, storage tanks and required equipment. The conversion from batch to integrated mode was achieved by extracting operating points and separation data from batch chromatograms. The integrated separation process was realized on an ÄKTA Pure controlled by a newly developed software called Orbit. The setup consisted of two column …
Continuous Gas Processing Without Bubbles Using Thin Liquid Film Bioreactors Containing Biocomposite Biocatalysts, Michael C. Flickinger, Orlin D. Velev, Mark J. Schulte, Adam Wallace, Christopher Duran, Nilay Chakraborty, Michael Guarnieri, Kamelia Boodhoo
Continuous Gas Processing Without Bubbles Using Thin Liquid Film Bioreactors Containing Biocomposite Biocatalysts, Michael C. Flickinger, Orlin D. Velev, Mark J. Schulte, Adam Wallace, Christopher Duran, Nilay Chakraborty, Michael Guarnieri, Kamelia Boodhoo
Integrated Continuous Biomanufacturing III
Continuous microbial gas processing without bubbles is possible with thin liquid film, plug flow bioreactors. We have demonstrated that power input can be minimized by using a falling liquid film operating under laminar wavy flow conditions (Re <200) in contact with highly concentrated living, non-growing microbes stabilized in a porous biocomposite biocatalyst. This composite materials approach to continuous gas processing can dramatically increase mass transfer rates >100 fold compared to bubble aeration, decrease process volume, significantly decrease gas-liquid mass transfer energy input, decrease water use, and increase secreted product concentration. We have shown that this approach can also increase microbial specific activity for some organisms compared to microbes suspended in liquid media. Paper-based biocomposite biocatalysts provide a rough hydrophilic surface resulting in uniform ~300 μm thick falling liquid films. …
Cost Modeling Of An Integrated, Continuous Downstream Mab Platform, Mark Schofield
Cost Modeling Of An Integrated, Continuous Downstream Mab Platform, Mark Schofield
Integrated Continuous Biomanufacturing III
Continuous manufacturing offers great potential for reducing costs in biopharmaceutical production through process intensification. However, adoption of new manufacturing methods and technologies is dependent on proof that the risk is worth the reward. Here Pall Life Science’s integrated, continuous downstream mAb platform is modeled in BioSolve Process. Supporting information is generated from a real, PD scale continuous platform. Perfusion and traditional fed batch cell culture processes are also modeled in both stainless steel and single-use forms. The cost associated with these three downstream strategies are compared across a range of bioreactor volumes, titers, and number of batches per year. This …
Development Of A Scale Down Toolbox For Perfusion Process Development, Jean-Marc Bielser
Development Of A Scale Down Toolbox For Perfusion Process Development, Jean-Marc Bielser
Integrated Continuous Biomanufacturing III
Background and novelty Merck KGaA has a legacy of perfusion manufacturing processes with several commercial products that were developed in the 90s. These processes were developed for adherent cell systems. Since then, with the advances in media design and the monoclonal antibody driven portfolio, development efforts have been focusing on fed-batch with suspended cells. Recently and as many players in the biomanufacturing industry, Merck is working on the development of an integrated continuous process. To support this effort a process development platform for perfusion cell culture needs to be developed. Process development for fed-batch is clearly defined and scale down …
Novel Concepts For Efficient And Predictable Membrane Separation In Continuous Cell Retention And Downstream Processing, Ulrich Kulozik, Martin Hartinger, Maria Weinberger
Novel Concepts For Efficient And Predictable Membrane Separation In Continuous Cell Retention And Downstream Processing, Ulrich Kulozik, Martin Hartinger, Maria Weinberger
Integrated Continuous Biomanufacturing III
Membranes are applied in biotechnological operations for sterile filtration, cell retention during continuous oper-ation, and cell separation as the first step after fermentation. Membranes are also in use in various steps during purification and isolation of certain target components. In all applications the retained substances, mainly bio-genic material such as cells, protein or polysaccharides, form a deposited layer at the membrane surface. This layer acts as an often dominating secondary membrane, which affects the permeability of the whole system more than the membrane as such. Thus, predictability, efficiency and consistency of all affected processing steps are impaired, which might create …
Process Analytical Technology (Pat) In Continuous Bioprocessing, Edita Botonjic-Sehic
Process Analytical Technology (Pat) In Continuous Bioprocessing, Edita Botonjic-Sehic
Integrated Continuous Biomanufacturing III
In recent years biotech companies have been emphasizing on the implementation and utilization of process analytical technology (PAT) in continuous bioprocessing. An overview of PAT concepts for biotech processes with emphasis on integrated continuous bioprocessing and production of monoclonal antibodies will be presented. Biotech processes consist of several unit operations, with each unit operation serving a defined purpose. For some of the product quality attributes, a certain level of redundancy in the process is expected. The need for appropriate control of each step and continuous evaluation of its performance is of great importance. The objective of commonly used unit operations …
Supervisory Control Of Integrated Continuous Downstream Processes, Bernt Nilsson, Anton Löfgren, Joaquin Gomis Fons, Niklas Andersson, Lotta Berghard
Supervisory Control Of Integrated Continuous Downstream Processes, Bernt Nilsson, Anton Löfgren, Joaquin Gomis Fons, Niklas Andersson, Lotta Berghard
Integrated Continuous Biomanufacturing III
Smart downstream processing can be performed with a sequence of integrated purification steps, which minimize the number of storage tanks and reduce hold-up time. The result is an integrated unit operation sequence that performs straight through processing of the target protein, with minimal time from expression to formulation. This downstream processing technique is well suited to be connected to a continuous upstream process based on perfusion. To develop these kinds of processes it is important to do studies in small-scale in a convenient way. This paper presents a methodology for supervisory control of integrated continuous downstream processes in lab-scale. A …
Use Of A Biphasic Perfusion Process Based On Mild Hypothermia For Recombinant Glucocerebrosidase (Gba) Production, Filipa Gonçalves, Juliana Coronel, Leda R. Castilho
Use Of A Biphasic Perfusion Process Based On Mild Hypothermia For Recombinant Glucocerebrosidase (Gba) Production, Filipa Gonçalves, Juliana Coronel, Leda R. Castilho
Integrated Continuous Biomanufacturing III
The main goal of this study was to develop an innovative CHO-based process for the production of glucocerebrosidase (GBA), an enzyme used for the replacement therapy of Type 1 Gaucher disease. The focus of the present study was on the development of a perfusion process, combining strategies that are commonly used for process optimization: temperature reduction, and supplementation of the culture medium with productivity enhancers, such as short chain fatty acids. The effects of mild hypothermic conditions combined with valeric acid supplementation were first studied in batch shake flasks for two clones (CHO-GBA-36K and CHO-GBA-65P), developed previously using as host …
Qualification Of Single Use In-Line Sensors For Use In Continuous Bioprocessing, James Furey, Dennis Annarelli, Josh Huang
Qualification Of Single Use In-Line Sensors For Use In Continuous Bioprocessing, James Furey, Dennis Annarelli, Josh Huang
Integrated Continuous Biomanufacturing III
The requirements for batch versus continuous processing will be compared along the lines of the design attributes of single use sensors for pressure, temperature, conductivity, and UV absorbance and also performance over months of continuous operation. These sensors are applicable in both upstream and downsteam processing starting with pressure monitoring on single use bioreactors, sensors required for perfusion process monitoring followed by monitoring of continuous purification processes. Dissection of the materials of the sensors and their physical nature to withstand liquid exposure of up to 90 days versus (versus shorter more discrete batch processes of less than one day) will …
Up And Down Scale Considerations For The Continuous Production Of Glycooptimized Biopharmaceuticals, Steffen Kreye, Rainer Stahn
Up And Down Scale Considerations For The Continuous Production Of Glycooptimized Biopharmaceuticals, Steffen Kreye, Rainer Stahn
Integrated Continuous Biomanufacturing III
Product quality especially with respect to glycosylation is a critical product attribute which can have an immense influence on the activity of glycoproteins and should be closely monitored during process development and manufacturing. GlycoExpressTM cells have been developed in this context to provide human host cell lines with robust glycosylation machineries. This work will address challenges in two case studies for up and down scaling of production processes with focus on product quality and continuous processing. In a first section, data of a process transfer from a 200 L stainless steel to a 1000 L single-use bioreactor for a continuous …
Application Of Single Pass Tff To Enable Intensified And Continuous Biological Manufacturing, Herb Lutz
Application Of Single Pass Tff To Enable Intensified And Continuous Biological Manufacturing, Herb Lutz
Integrated Continuous Biomanufacturing III
No abstract provided.
Fouling Mitigation In Membrane Based Perfusion Systems By Oscillating Tangential Flow, Maria Weinberger, Ulrich Kulozik
Fouling Mitigation In Membrane Based Perfusion Systems By Oscillating Tangential Flow, Maria Weinberger, Ulrich Kulozik
Integrated Continuous Biomanufacturing III
Good scalability and robust handling have promoted the application of membrane based cell retention devices. A physical barrier, i.e. a filter, retains cells and cell debris. One major drawback of these devices is their ten-dency to foul and clog. One form of fouling is deposit layer formation on the filter surface, consisting of cells, cell debris and other fermentation broth constituents. This leads to the build-up of a secondary membrane, which can alter the permeation profile. Furthermore, deposit layers lead to an increased filtration resistance and thus negatively affect permeate flux, filtration efficiency and process robustness. In tangential flow filtration, …
Ultra Scale-Down Mimics For Perfusion Culture: Experimental Study For Rapid Biopharmaceutical Process Development, Molly Tregidgo, Martina Micheletti, David Pollard
Ultra Scale-Down Mimics For Perfusion Culture: Experimental Study For Rapid Biopharmaceutical Process Development, Molly Tregidgo, Martina Micheletti, David Pollard
Integrated Continuous Biomanufacturing III
With the industry driving towards the implementation of whole continuous bioprocess sequences, there becomes a requirement for the development of scale-down tools with the same consistency, reliability and throughput as those already available for traditional batch processes. This work aims to develop a perfusion scale-down system capable of reproducing the specific characteristics of the perfusion culture process, namely cell retention capabilities, the ability to support high cell densities and to operate for extended periods compared to fed-batch cultures. Cell culture in microwell plates in fed-batch mode is well defined and is in widespread use; however to the best of our …
Conference Program, Suzanne Farid, Chetan Goudar, Paula Alves, Veena Warikoo
Conference Program, Suzanne Farid, Chetan Goudar, Paula Alves, Veena Warikoo
Integrated Continuous Biomanufacturing III
No abstract provided.
Optimizing Media For Perfusion Combining Predictive Scale-Down Models And Multivariate Approaches, Jochen Sieck, Christian Schultheiss, Pedro Felizardo
Optimizing Media For Perfusion Combining Predictive Scale-Down Models And Multivariate Approaches, Jochen Sieck, Christian Schultheiss, Pedro Felizardo
Integrated Continuous Biomanufacturing III
Perfusion medium development is complex and time-consuming. Thus, a methodology for efficient and cost effective development leading to a significant reduction of time to market is key in today's competitive market. Success in perfusion medium development depends strongly on the choice of optimization tools. Here a streamlined strategic approach to accentuate perfusion media development is presented by means of predictive scale down models and the application of Design of Experiments (DOE). The purpose of the study was to investigate the impact of 19 amino acids on productivity and growth of a CHO-K1 cell line in perfusion cell culture. A stepwise …
Clarification And Capture Of A Cho-Derived Monoclonal Antibody Through Flocculation And Aex Processes, Rimenys J. Carvalho, Leda Castilho
Clarification And Capture Of A Cho-Derived Monoclonal Antibody Through Flocculation And Aex Processes, Rimenys J. Carvalho, Leda Castilho
Integrated Continuous Biomanufacturing III
Flocculants have been widely used in the food and chemical industry, as well as in wastewater clarification. More recently, studies have shown the applicability of these agents in the clarification of mammalian cell suspensions as an alternative e.g. to centrifugation and microfiltration1,2. Flocculants present several advantages such as low cost, process simplicity and facility to run under continuous mode. On the other hand, some flocculants have shown toxicity and thus their total clearance has to be demonstrated. In this work, the cationic flocculants chitosan and poly diallyldimethylammonium chloride (PDADMAC) have been investigated and compared for the clarification of suspensions of …
Development And Application Of Screening Scale Bioreactor Systems For Very High Cell Density Perfusion Of Mammalian Cells, Caijuan Zhan, Hubert Schwarz, Magnus Lundqvist, Atefeh Shokri, Ray Field, Richard Turner, Mathias Uhlén, Johan Rockberg, Veronique Chotteau
Development And Application Of Screening Scale Bioreactor Systems For Very High Cell Density Perfusion Of Mammalian Cells, Caijuan Zhan, Hubert Schwarz, Magnus Lundqvist, Atefeh Shokri, Ray Field, Richard Turner, Mathias Uhlén, Johan Rockberg, Veronique Chotteau
Integrated Continuous Biomanufacturing III
The development of cultivation processes can be significantly more efficient and cost effective when performed in parallel screening systems operated at small scale. Although perfusion systems at screening scale have been proposed, none of them enables a real mimic of very high cell density perfusion bioreactors. The latter is however important to maximize the performance of processes at 80, 100 x 106 cells/mL, or higher cell densities, in particular to optimize the nutrient supply and feeding regime. The purpose of the present work was to develop such a system and to apply it to perfusion optimization. Chinese Hamster Ovary cells …