The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
David Pollard - One of the best experts on this subject based on the ideXlab platform.
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automated disposable small scale bioreactor for high Throughput Process development implementation of the 24 bioreactor array
Pharmaceutical bioprocessing, 2015Co-Authors: Rachel Bareither, Neil Bargh, Robert Oakeshott, Marina Goldfeld, Chris Kistler, Andrew Tait, Kristin Oneill, Linda Hoshan, David PollardAbstract:Aim: A disposable reactor system (250 ml scale) has now been developed into a fully automated 24 reactor array which includes Process parameter monitoring and control, advanced feed strategies, automated event triggering, robotic arm liquid handling and sample storage. Results: Process and analytical comparability was shown for a range of Pichia, Escherichia coli and CHO cell-culture bioProcesses up to pilot and commercial scale. This established the system as a scale-down model for Process development and characterization of large-scale industrial Processes. Conclusion: This work demonstrated the ability of the automated system to accelerate Process development by executing a single statistical design of experiments, with a wider range of parameters, up to 3–5-times faster than conventional approaches.
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Automated disposable small scale reactor for high Throughput bioProcess development: a proof of concept study.
Biotechnology and Bioengineering, 2013Co-Authors: Rachel Bareither, Neil Bargh, Robert Oakeshott, Kathryn Watts, David PollardAbstract:The acceleration of bioProcess development for biologics and vaccines can be enabled by automated high Throughput technologies. This will alleviate the significant resource burden from the multi-factorial statistical experimentation required for controlling product quality attributes of complex biologics. Recent technology advances have improved clone evaluation and screening, but have struggled to combine the scale down criteria required for both high cell density cell culture and microbial Processes, with sufficient automation and disposable technologies to accelerate Process development. This article describes the proof of concept evaluations of an automated disposable small scale reactor for high Throughput upstream Process development. Characterization studies established the small scale stirred tank disposable 250 mL reactor as similar to those of lab and pilot scale. The reactor generated equivalent Process performance for industrial biologics Processes for therapeutic protein and monoclonal antibody production using CHO cell culture, Pichia pastoris and E. coli. This included similar growth, cell viability, product titer, and product quality. The technology was shown to be robust across multiple runs and met the requirements for the ability to run high cell density Processes (>400 g/L wet cell weight) with exponential feeds and sophisticated event triggered Processes. Combining this reactor into an automated array of reactors will ultimately be part of a high Throughput Process development strategy. This will combine upstream, small scale purification with rapid analytics that will dramatically shorten timelines and costs of developing biological Processes.
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A review of advanced small-scale parallel bioreactor technology for accelerated Process development: Current state and future need
Biotechnology Progress, 2011Co-Authors: Rachel Bareither, David PollardAbstract:The pharmaceutical and biotech industries face continued pressure to reduce development costs and accelerate Process development. This challenge occurs alongside the need for increased upstream experimentation to support quality by design initiatives and the pursuit of predictive models from systems biology. A small scale system enabling multiple reactions in parallel (n ≥ 20), with automated sampling and integrated to purification, would provide significant improvement (four to fivefold) to development timelines. State of the art attempts to pursue high Throughput Process development include shake flasks, microfluidic reactors, microtiter plates and small-scale stirred reactors. The limitations of these systems are compared to desired criteria to mimic large scale commercial Processes. The comparison shows that significant technological improvement is still required to provide automated solutions that can speed upstream Process development.
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a review of advanced small scale parallel bioreactor technology for accelerated Process development current state and future need
Biotechnology Progress, 2011Co-Authors: Rachel Bareither, David PollardAbstract:The pharmaceutical and biotech industries face continued pressure to reduce development costs and accelerate Process development. This challenge occurs alongside the need for increased upstream experimentation to support quality by design initiatives and the pursuit of predictive models from systems biology. A small scale system enabling multiple reactions in parallel (n ≥ 20), with automated sampling and integrated to purification, would provide significant improvement (four to fivefold) to development timelines. State of the art attempts to pursue high Throughput Process development include shake flasks, microfluidic reactors, microtiter plates and small-scale stirred reactors. The limitations of these systems are compared to desired criteria to mimic large scale commercial Processes. The comparison shows that significant technological improvement is still required to provide automated solutions that can speed upstream Process development. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Rachel Bareither - One of the best experts on this subject based on the ideXlab platform.
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automated disposable small scale bioreactor for high Throughput Process development implementation of the 24 bioreactor array
Pharmaceutical bioprocessing, 2015Co-Authors: Rachel Bareither, Neil Bargh, Robert Oakeshott, Marina Goldfeld, Chris Kistler, Andrew Tait, Kristin Oneill, Linda Hoshan, David PollardAbstract:Aim: A disposable reactor system (250 ml scale) has now been developed into a fully automated 24 reactor array which includes Process parameter monitoring and control, advanced feed strategies, automated event triggering, robotic arm liquid handling and sample storage. Results: Process and analytical comparability was shown for a range of Pichia, Escherichia coli and CHO cell-culture bioProcesses up to pilot and commercial scale. This established the system as a scale-down model for Process development and characterization of large-scale industrial Processes. Conclusion: This work demonstrated the ability of the automated system to accelerate Process development by executing a single statistical design of experiments, with a wider range of parameters, up to 3–5-times faster than conventional approaches.
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Automated disposable small scale reactor for high Throughput bioProcess development: a proof of concept study.
Biotechnology and Bioengineering, 2013Co-Authors: Rachel Bareither, Neil Bargh, Robert Oakeshott, Kathryn Watts, David PollardAbstract:The acceleration of bioProcess development for biologics and vaccines can be enabled by automated high Throughput technologies. This will alleviate the significant resource burden from the multi-factorial statistical experimentation required for controlling product quality attributes of complex biologics. Recent technology advances have improved clone evaluation and screening, but have struggled to combine the scale down criteria required for both high cell density cell culture and microbial Processes, with sufficient automation and disposable technologies to accelerate Process development. This article describes the proof of concept evaluations of an automated disposable small scale reactor for high Throughput upstream Process development. Characterization studies established the small scale stirred tank disposable 250 mL reactor as similar to those of lab and pilot scale. The reactor generated equivalent Process performance for industrial biologics Processes for therapeutic protein and monoclonal antibody production using CHO cell culture, Pichia pastoris and E. coli. This included similar growth, cell viability, product titer, and product quality. The technology was shown to be robust across multiple runs and met the requirements for the ability to run high cell density Processes (>400 g/L wet cell weight) with exponential feeds and sophisticated event triggered Processes. Combining this reactor into an automated array of reactors will ultimately be part of a high Throughput Process development strategy. This will combine upstream, small scale purification with rapid analytics that will dramatically shorten timelines and costs of developing biological Processes.
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A review of advanced small-scale parallel bioreactor technology for accelerated Process development: Current state and future need
Biotechnology Progress, 2011Co-Authors: Rachel Bareither, David PollardAbstract:The pharmaceutical and biotech industries face continued pressure to reduce development costs and accelerate Process development. This challenge occurs alongside the need for increased upstream experimentation to support quality by design initiatives and the pursuit of predictive models from systems biology. A small scale system enabling multiple reactions in parallel (n ≥ 20), with automated sampling and integrated to purification, would provide significant improvement (four to fivefold) to development timelines. State of the art attempts to pursue high Throughput Process development include shake flasks, microfluidic reactors, microtiter plates and small-scale stirred reactors. The limitations of these systems are compared to desired criteria to mimic large scale commercial Processes. The comparison shows that significant technological improvement is still required to provide automated solutions that can speed upstream Process development.
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a review of advanced small scale parallel bioreactor technology for accelerated Process development current state and future need
Biotechnology Progress, 2011Co-Authors: Rachel Bareither, David PollardAbstract:The pharmaceutical and biotech industries face continued pressure to reduce development costs and accelerate Process development. This challenge occurs alongside the need for increased upstream experimentation to support quality by design initiatives and the pursuit of predictive models from systems biology. A small scale system enabling multiple reactions in parallel (n ≥ 20), with automated sampling and integrated to purification, would provide significant improvement (four to fivefold) to development timelines. State of the art attempts to pursue high Throughput Process development include shake flasks, microfluidic reactors, microtiter plates and small-scale stirred reactors. The limitations of these systems are compared to desired criteria to mimic large scale commercial Processes. The comparison shows that significant technological improvement is still required to provide automated solutions that can speed upstream Process development. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Jurgen Hubbuch - One of the best experts on this subject based on the ideXlab platform.
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a sub two minutes method for monoclonal antibody aggregate quantification using parallel interlaced size exclusion high performance liquid chromatography
Journal of Chromatography A, 2011Co-Authors: Patrick Diederich, Sigrid K Hansen, Stefan A Oelmeier, Bianca Stolzenberger, Jurgen HubbuchAbstract:Abstract In Process development and during commercial production of monoclonal antibodies (mAb) the monitoring of aggregate levels is obligatory. The standard assay for mAb aggregate quantification is based on size exclusion chromatography (SEC) performed on a HPLC system. Advantages hereof are high precision and simplicity, however, standard SEC methodology is very time consuming. With an average Throughput of usually two samples per hour, it neither fits to high Throughput Process development (HTPD), nor is it applicable for purification Process monitoring. We present a comparison of three different SEC columns for mAb-aggregate quantification addressing Throughput, resolution, and reproducibility. A short column (150 mm) with sub-two micron particles was shown to generate high resolution (∼1.5) and precision (coefficient of variation (cv)
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a label free methodology for selective protein quantification by means of absorption measurements
Biotechnology and Bioengineering, 2011Co-Authors: Sigrid K Hansen, Erik Skibsted, Arne Staby, Jurgen HubbuchAbstract:The application of high Throughput experimentation (HTE) in protein purification Process development has created an analytical bottleneck. Using a new label-free and non-invasive methodology for analyzing multicomponent protein mixtures by means of spectral measurements, we show that the analytical Throughput for selective protein quantification can be increased significantly. An analytical assay based on this new methodology was shown to generate very precise results. Further, the assay was successfully applied as analytics for a resin screening performed in HTE mode. The increase in analytical Throughput was obtained without decreasing the level of information when compared to analytical chromatography. This proves its potential as a valuable analytical tool in conjugation with high Throughput Process development (HTPD). Further, fast selective protein quantification can enhance Process control in a commercial production environment and, hence, minimize the need for off-line release analysis.
Anurag S Rathore - One of the best experts on this subject based on the ideXlab platform.
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chromatography Process development in the quality by design paradigm i establishing a high Throughput Process development platform as a tool for estimating characterization space for an ion exchange chromatography step
Biotechnology Progress, 2013Co-Authors: Rahul Bhambure, Anurag S RathoreAbstract:This article describes the development of a high-Throughput Process development (HTPD) platform for developing chromatography steps. An assessment of the platform as a tool for establishing the “characterization space” for an ion exchange chromatography step has been performed by using design of experiments. Case studies involving use of a biotech therapeutic, granulocyte colony-stimulating factor have been used to demonstrate the performance of the platform. We discuss the various challenges that arise when working at such small volumes along with the solutions that we propose to alleviate these challenges to make the HTPD data suitable for empirical modeling. Further, we have also validated the scalability of this platform by comparing the results from the HTPD platform (2 and 6 μL resin volumes) against those obtained at the traditional laboratory scale (resin volume, 0.5 mL). We find that after integration of the proposed correction factors, the HTPD platform is capable of performing the Process optimization studies at 170-fold higher productivity. The platform is capable of providing semi-quantitative assessment of the effects of the various input parameters under consideration. We think that platform such as the one presented is an excellent tool for examining the “characterization space” and reducing the extensive experimentation at the traditional lab scale that is otherwise required for establishing the “design space.” Thus, this platform will specifically aid in successful implementation of quality by design in biotech Process development. This is especially significant in view of the constraints with respect to time and resources that the biopharma industry faces today. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 403–414, 2013
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high Throughput Process development for biopharmaceutical drug substances
Trends in Biotechnology, 2011Co-Authors: Rahul Bhambure, Kaushal Kumar, Anurag S RathoreAbstract:Quality by Design (QbD) is gaining industry acceptance as an approach towards development and commercialization of biotechnology therapeutic products that are expressed via microbial or mammalian cell lines. In QbD, the Process is designed and controlled to deliver specified quality attributes consistently. To acquire the enhanced understanding that is necessary to achieve the above, however, requires more extensive experimentation to establish the design space for the Process and the product. With biotechnology companies operating under ever-increasing pressure towards lowering the cost of manufacturing, the use of high-Throughput tools has emerged as a necessary enabler of QbD in a time- and resource-constrained environment. We review this topic for those in academia and industry that are engaged in drug substance Process development.
Won Jun Choi - One of the best experts on this subject based on the ideXlab platform.
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Ultra-high-Throughput Production of III-V/Si Wafer for Electronic and Photonic Applications
Scientific Reports, 2016Co-Authors: Dae-myeong Geum, Min-su Park, Ju Young Lim, Hyun-duk Yang, Jin Dong Song, Chang Zoo Kim, Euijoon Yoon, Sanghyeon Kim, Won Jun ChoiAbstract:Si-based integrated circuits have been intensively developed over the past several decades through ultimate device scaling. However, the Si technology has reached the physical limitations of the scaling. These limitations have fuelled the search for alternative active materials (for transistors) and the introduction of optical interconnects (called “Si photonics”). A series of attempts to circumvent the Si technology limits are based on the use of III-V compound semiconductor due to their superior benefits, such as high electron mobility and direct bandgap. To use their physical properties on a Si platform, the formation of high-quality III-V films on the Si (III-V/Si) is the basic technology ; however, implementing this technology using a high-Throughput Process is not easy. Here, we report new concepts for an ultra-high-Throughput heterogeneous integration of high-quality III-V films on the Si using the wafer bonding and epitaxial lift off (ELO) technique. We describe the ultra-fast ELO and also the re-use of the III-V donor wafer after III-V/Si formation. These approaches provide an ultra-high-Throughput fabrication of III-V/Si substrates with a high-quality film, which leads to a dramatic cost reduction. As proof-of-concept devices, this paper demonstrates GaAs-based high electron mobility transistors (HEMTs), solar cells, and hetero-junction phototransistors on Si substrates.