Biomedical Engineering and Bioengineering Commons^™

Evaluation Of A Continuous Chromatography Process Through Process Modeling And Resin Characterization, Ketki Behere, Seongkyu Yoon

Integrated Continuous Biomanufacturing II

Increased product yield at reduced cost and time has been the driving force of any manufacturing process. However, inevitable increase in future demand for biopharmaceutical drugs, along with intensified competition and stringent regulatory laws have exhibited an imperative need for established platform processes. In this regard, the implementation of continuous processing, in whole or in components, has demonstrated to increase the manufacturing productivity with key impact on speed, cost and facility implications. While, upstream operations have confirmed increased productivity by implementation of continuous processing components, such as perfusion culture, similar adaptation for downstream processes has been limited. We have evaluated …

Continuous Production Of Proteins: Integration Of Polishing Using Mcsgp, Fabian Steinebach, Daniel Karst, Massimo Morbidelli

Integrated Continuous Biomanufacturing II

Continuous counter-current processes for polishing steps overcome the purity-yield tradeoff of classical batch chromatography by internal recycling of overlapping regions of the chromatogram. Particularly in the case of challenging separation tasks this leads for the same product quality to significantly higher yields and productivity. Processes using these fundamental principals have been successfully implemented in the chemical industry up to multi-ton production.

In an integrated continuous process, with a perfusion bioreactor and a continuous capture process, the product quality of the capture product is different compared to classical batch processing. The lower residence time in the bioreactor and the higher loading …

Exometabolome Characterization Of High Cell Density Culture Perfusion And Optimization Of The Cell Specific Perfusion Rate, Veronique Chotteau, Leila Zamani, Ye Zhang, Magnus Aberg, Anna Lindahl, Axel Mie

Integrated Continuous Biomanufacturing II

High cell density perfusion has the potential to generate intensified processes. A target for such perfusion process can be to maintain a steady state culture around 100 x 10⁶ cells/mL. A challenge for the development of these processes is to minimize the medium consumption, to reduce the costs associated with this raw material and with the harvest processing. This is particularly true for processes at densities such as 100 x 10⁶ cells/mL for which several reactor volumes per day are typically necessary.

We have shown that cell specific perfusion rate (CSPR) is an approach, which has proven to …

Continuous Downstream Processing Of A Monoclonal Antibody Using Periodic Counter Current Chromatography (Pcc) And Straight Through Processing (Stp), Hans Blom, Christer Eriksson, Annika Forss, Helena Skoglar

Integrated Continuous Biomanufacturing II

There is an increased interest to perform process intensification in order to reduce costs and improve throughput in the development and production of monoclonal antibodies (MAbs). One solution to these demands can be to implement continuous or semi-continuous downstream processing. New emerging technologies such as periodic counter-current (PCC) chromatography and straight through processing (STP) are entering the market. Here, these two technologies were evaluated in a continuous three step chromatography MAb process. The capture step was performed with protein A media (resin) on a 3 column PCC chromatography system followed by two polishing steps which were connected in series with …

Integrated Solutions For Continuous Processing In Mobius® Bioreactor Systems, Andrew Clutterbuck

Integrated Continuous Biomanufacturing II

Throughout the bioprocess industry, the use of disposable systems such as bioreactors is playing an increasingly significant role. Manufactures are recognising the strategic benefits of single use systems in both reducing production costs and increasing overall manufacturing throughput.

Over the past few years there has been increasing demand for larger scale disposable bioreactor systems, to satisfy the manufacturing demands and an emphasis on suppliers such as Merck Millipore to demonstrate robust and reproducible scale-up within these systems.

This presentation will explore the design philosophies behind the Mobius^® bioreactors and will also give an overview of the novel SensorReady external …

Optical Enzymatic Sensors For Continuous Monitoring Of Bioreactors, Kenneth Reardon, Brian Heinze, Trenton Danna

Integrated Continuous Biomanufacturing II

Continuous monitoring of biotechnological processes is important for control and optimization of quality and productivity. Typically, samples must be removed from the cultivation and analyzed in a laboratory to determine the concentrations of substrates and products. These time-delayed data cannot be used for real-time process control. The Process Analytical Technology initiative of the FDA supports the use of on-line measurement techniques for process development, production, and quality. An overview of sensors will be presented, focusing on in-situ sensors that contact the biological medium, and external sensors that contact the medium either optically (ex situ) or via a sterile (and disposable) …

Salt-Tolerant Cation Exchange Hd-Sb Hydrogel Membrane: Mab Purification Performance In Flowthrough Mode, Dharmesh Kanani, Daniel Luo, Nirali Paghdal, Navneet Sidhu, Annabel Shang, Jim Stout

Integrated Continuous Biomanufacturing II

Development of Protein A based purification platforms have simplified the downstream processing of monoclonal antibodies (mAb), the largest component of biopharmaceuticals. The ever increasing titer of the cell culture process is putting more pressure on the downstream process to further increase its productivity. The classical Protein A based mAb purification platform consists of two polishing steps, bind and elute cation-exchanger and flowthrough anion-exchanger. Cation-exchange chromatography is very efficient at the separation of HCP, leached Protein A and product-related impurities such as aggregates and fragments in bind and elute mode. However, anion-exchange chromatography is a proven technology to remove DNA, viruses, …

Glycoexpress: A Toolbox For The High Yield Production Of Glycooptimized Fully Human Biopharmaceuticals In Perfusion Bioreactors At Different Scales, Steffen Kreye

Integrated Continuous Biomanufacturing II

Background and Novelty: Glycosylation is one of the major post-translational modifications of biotherapeutics important for bioactivity, bioavailability, immunogenicity and patient coverage. By establishment of the GlycoExpress™ toolbox (GEX™) we have generated a set of glycoengineered human cell lines for the high yield production of fully human glycoproteins to optimize the glycosylation of antibodies and non-antibody biotherapeutics for improvement of the clinical efficacy and side effects. The system is biotechnologically superior in quality, reproducibility and yield compared to other including conventional production systems. All four clinical products derived from GlycoExpress cells are produced using a perfusion bioreactor system in order to …

Designing A Microbial Cultivation Platform For Continuous Biopharmaceutical Production, Nicholas Mozdzierz, Kerry Love, Alan Stockdale, John Clark, Noelle Colant, Christopher Love

Integrated Continuous Biomanufacturing II

The existing biopharmaceutical manufacturing paradigm is poorly suited to produce biologic drugs on demand at a point-of-care. Generally, commercial-scale (~2,000 - 10,000 L) manufacturing using fed-batch cultivation and fixed stainless-steel infrastructure is concentrated in developed nations and results in process cycle times on the order of weeks to months.^1,2 Coupled with the complex logistical challenges associated with continuous “plant-to-patient” cold-chains, the geographically biased nature of therapeutic protein production today can limit access to biologic drugs in developing areas of the world.³ There is an opportunity to create technologies capable of rapidly generating biopharmaceuticals in situ in emergency situations, …

Robust Design And Operation Of Quasi-Continuous Adenovirus Purification By Two-Column, Simulated Moving-Bed, Size-Exclusion Chromatography, Jose Mota, Ricardo Silva, Piergiuseppe Nestolla, Cristina Peixoto, Manuel Carrondo

Integrated Continuous Biomanufacturing II

Adenoviruses (Ads) are considered one of the most suitable platforms for production of viral vaccines and gene therapy vectors. Their broad tissue tropism and large transgene packing capacity make them attractive candidates for innovative virotherapies. Ads can be produced in a complementary cell line in both adherent and suspension culture systems, such as HEK-293 or PER-C6 cells, or A549 for oncolytic therapies.

Liquid chromatography is currently the core technique for vector purification, and its use is often integrated vertically within the downstream processing (DSP) strategy, as it easily fits into the early capture stage as well as into the final …

Final Program, Kathy Chan

Integrated Continuous Biomanufacturing II

No abstract provided.

Towards Continuous Aqueous Two-Phase Extraction (Catpe), Bettina Bommarius, Andres Bommarius, Irene Kaplanow, Julianne Merz, Gerhard Schembecker

Integrated Continuous Biomanufacturing II

Aqueous Two-Phase Extraction (ATPE) in mixer-settlers offers a gentle and biocompatible environment to separate proteins from complex mixtures. We have developed an aqueous two-phase system with inexpensive and biocompatible PEG 1500 or 4000 and ammonium citrate. We have purified several dehydrogenases [1] to near homogeneity after forward extraction into a PEG-heavy top phase at pH > 9 and back extraction into a bottom phase at pH 4-6; in selected cases, we were able to obtain pure protein in the bottom phase without forward extraction into the top phase. We have scaled up the PEG 1500/4000-ammonium citrate to a 5-10 L scale, …

Implementation Of Raman Spectroscopy At Manufacturing Scale: Overcoming Modeling Challenges While Implementing Advanced Process Control, John Smelko, Thomas Matthews, Brandon Berry, Douglas Osborne

Cell Culture Engineering XV

In order to improve glycation control in our new high intensity platform process, we investigated implementation of Raman spectroscopy to monitor and control glucose at low levels throughout the process. Using Raman allows a way to measure glucose near real time which in turn allows for a more responsive and flexible control algorithm. Prior literature has shown connections between elevated glucose levels and glycation when in presence of high protein concentrations, which was indicative of our process. Using Raman along with advanced process control (APC), allowed us the flexibility to reduce glycation back towards historical process levels.

We will share …

Comprehensive T Cell Antigen Discovery Using A Genomic Approach, Jessica Baker

Vaccine Technology IV

No abstract provided.

An Information Architecture For Icme, William Marsden

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

Multiscale Modeling For Material Design Of Solid Oxide Fuel Cell Electrode, Y. Umeno, S. Hara, T. Tada, N. Shikazono

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

Some (Other) Uses Of Diffusion Couples In Metallurgy: Model Calibration And Mapping Transitions In Mechanisms, Christopher Hutchinson

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

From Genome To Flying Cyberalloys: The First Half Century, G. B. Olson

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

A Hybrid Computational-Experimental Approach For Automated Crystal Structure Solution, Bryce Meredig, Scott Kirklin, Chris Wolverton

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

Predicting Microstructure-Property Relationships In Structural Materials Via Multiscale Models Validated By In-Situ Synchrotron Observation, Peter D. Lee, Lang Yuan, Chedtha Puncreobutr, S. Karagadde

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

Nist Databases For Materials Research, T. Vanderah, Vicky Karen, Peter Linstrom, Donald Burgess

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

The Materials Project – A Public Materials Design Platform, Kristin Persson

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

New Stage Of Matnavi, Materials Database At Nims, Toshio Ogata, Masayoshi Yamazaki

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

Materials Design Based On Ab Initio Thermodynamics, Jorg Neugebauer, Fritz Kormann, Blazej Grabowski, Tilmann Hickel, Dierk Raabe

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

Materials Property Microscopy Tools For The Materials Genome Initiative, J. C. Zhao, David Cahill

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

High-Throughput Synthesis And Analysis For Searching New Permanent Magnet Materials, Gerhard Schneider, Dagmar Goll, Ralf Loffller, Roman Karimi

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

A Software Framework For Designing Material, David Cebon, Mike Ashby

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

Atomis'c Materials Design Using The Computa'onal Materials Repository, Karsten W. Jacobsen

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

High Throughput Mapping Of The Thermophysical Properties Of Materials, David G. Cahill, Xuan Zheng, Wen-Pin Hsieh, J. C. Zhao

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

No abstract provided.

Conference Program, Engineering Conferences International

Harnessing The Materials Genome: Accelerated Materials Development via Computational and Experimental Tools

highlighted titles are available online documents.