Cambridge Healthtech Institute’s 4th Annual
Advances in Purification Technologies
Improved Methods and New Advances in Downstream Processing
Part of CHI's Ninth Annual The Bioprocessing Summit
August 23 - 24, 2017 | Westin Copley Place | Boston, MA
Downstream processing is an area ripe for technology innovations. With higher upstream titers creating bottlenecks in downstream, and high cost of proteinA resins, the downstream steps are not only cumbersome, but also inefficient and costly. With single-use
technologies and continuous processing making headways into downstream processing and offering cost-savings, higher productivity gains and faster turnarounds, companies are now looking for alternative technologies that can further revolutionize the
downstream industry. These include alternatives to proteinA, alternatives to cell culture clarification, membrane filtration technologies, depth filtration, new adsorbents, novel precipitation and flocculation techniques, etc.
CHI’s 3rd Annual Advances in Purification Technologies brings together scientists who are exploring these alternative techniques to share their experiences, discuss their goals and gains, as well as offer advice on challenges to overcome and
pitfalls to avoid.
Wednesday, August 23
7:00 am Registration Open and Morning Coffee
8:05 Chairperson’s Opening Remarks
Stefano Menegatti, Ph.D., Assistant Professor, Department of Chemical and Biochemical Engineering, NC State University
8:15 KEYNOTE PRESENTATION:
Protein Engineering and Evolving Demands in Protein Purification: A Critical Appraisal of Workflow Options in Downstream Processing
David O’Connell, Ph.D., Lecturer in Biotherapeutics, School of Biomolecular & Biomedical
Science, University College Dublin
This presentation will review the area of purification of fusion proteins, antibody fragments, gene therapies, and virus and vaccine therapies, and feature case studies highlighting innovative approaches to their improved recovery.
9:00 Downstream Process Development of an in vivo Radiolabeled Protein Diagnostic Expressed in E. coli
Brian O’Mara, Senior Scientist, Bioprocess Development, Bristol-Myers Squibb
Standard pathological diagnostic applications utilize immunohistochemistry (IHC) techniques to detect specific tumor associated antigens of biopsied tissues using antibodies labeled with a reporter molecule. The usefulness of IHC as a diagnostic tool
is limited by the small sample size of the biopsy which may either miss or underestimate the extent of the disease. Here we discuss the process development of an E. coli expressed radiolabeled protein conjugate used
for the in vivo diagnosis of a specific tumor antigen.
9:30 Purification of Common Light Chain IgG-Like Bispecific Antibodies Using Highly Linear pH Gradients
Beth Sharkey, Associate Scientist, High Throughput Expression, Adimab, LLC
This talk will demonstrate an approach to producing bispecific antibodies that deviates from the strategy of introducing potentially undesirable mutations to enable manufacturing. Instead, a high resolution purification method is leveraged to generate
a panel of entirely native common light chain bispecific antibodies. The technique is compatible with ion exchange resins that are suitable for industrial scale applications and can be used for other bispecific antibody formats as well.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Advances and New Approaches in Affinity Chromatography
Krunal Mehta, Ph.D., Scientist, Purification Process Development, Amgen
The high cost of Protein A resins has required better utilization of its capacity or the use of cheaper and comparable alternatives to improve the downstream process economics. While the improvements in capacities have been limited, achieving higher operational
flow rates has led to much more dramatic improvements in the productivity of Protein A capture step. The significantly higher productivity through substantially reduced cycle times enables better resin utilization and reduces the resin requirements
without compromising the throughput of the capture step.
11:15 Leveraging Affinity Capture to Also Select Critical Quality Attributes
Warren Kett, Ph.D., CSO, Avitide, Inc.
The challenges of purification are magnified when not only removal of host-derived impurities is difficult, but product related impurities also persist. We present case studies where we developed affinity resins for biopharmaceutical companies that met
both goals - a single affinity column that provided robust capture and also selected the correct product isoform. In addition to the obvious advantages of these dual functional resins, unforeseen process benefits also accrued.
11:45 A Novel Chromatographic Technology: Enhancing Performance Utilizing a Modular Lattice Supported Resin Bed
Masayoshi Nagaya, Global Technology Manager, Separation Science Group, JSR Life Sciences
Improvements in chromatography utilization have been focused mostly on resin design, buffer selection and operating modes. A novel technology that allows full bed support via a 3D printed internal lattice enables modular chromatography, prepacked ease
of use and enhanced productivity. Data will be shown to illustrate productivity improvement of several fold for a Protein A capture step.
12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:00 Session Break
1:45 Chairperson’s Remarks
David O’Connell, Ph.D., Lecturer in Biotherapeutics, School of Biomolecular & Biomedical Science, University College Dublin
1:50 Evaluation of Straight-Through Protein Chromatography to Enable Truly Continuous Bioprocessing
Stefano Menegatti, Ph.D., Assistant Professor, Department of Chemical and Biochemical
Engineering, NC State University
We have developed a technology that integrates proteomics tools with statistical-graphical methods to (1) determine the clearance of HCPs and (2) identify complementary technologies for HCP removal. To demonstrate, we evaluated the ability of commercial
chromatographic resins to remove HCPs from CHO-S supernatants. We have derived statistical correlations between % removal of each protein species and its isoelectric point, and identified 24 HCPs that were not removed by any of the resins studied.
2:20 Development of Next Generation mAb Purification Process
Tingting Cui, Ph.D., Scientist II, Purification Process Sciences, MedImmune Ltd., part of AstraZeneca
This case study demonstrates a systematic approach to adopt a ‘flow through’ process in designing purification of a mAb with high titer. As a result, the new downstream process enhances the process productivity by 3- fold, significantly
reduces buffer volumes by 10 fold and secures the product quality. This type of downstream process could be utilized for other potential high titers biotherapeutics.
2:50 Advances in Harvest Technologies
Glen Giese, Scientist, Group Leader, Purification Development, Genentech, Inc.
3:20 Efficient Devices for Process-Scale Chromatography
Raja Ghosh, Ph.D., Professor, Canada Research Chair in Bioseparations Engineering, Chemical Engineering,
This presentation focuses on a radically different approach of using a cuboid or “box-shaped” packed-bed instead of a “column”. The design of such a cuboid packed-bed is inspired by that of a laterally-fed membrane chromatography
device, also developed by the presenter. The workings of such devices, and how they could potentially play an important role in process-scale chromatography, are explained.
3:50 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 PLENARY KEYNOTE PRESENTATION
6:00 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 Close of Day
Thursday, August 24
8:00 am Registration Open and Morning Coffee
8:25 Chairperson’s Remarks
Raja Ghosh, Ph.D., Professor, Canada Research Chair in Bioseparations Engineering, Chemical Enginering, McMaster University
8:30 Buffer Concentrates: Improving Downstream Efficiency through Real-Time Monitoring, Release and Control
Veronica Adams, MSc, Engineer II, Process Biochemistry, Biogen
Two strategies which can increase efficiency in buffer preparation and storage include real time monitoring of buffer characteristics during preparation and the use of buffer concentrates. Real time monitoring via inline pH and conductivity probes
during buffer preparation and release can streamline preparation, reducing offline sampling for buffer release. Buffer concentrates can alleviate the volume requirements for increased buffer usage, reducing the storage footprint required.
9:00 BioXcellence Tech Transfer Concept – An Insight in General Tech Transfer Approach Including BI’s Quality Culture Initiative
Daniel Kronberger, MSc, Head of Downstream Pilot, Process Sciences, Boehringer Ingelheim
RCV GmbH & Co. KG
The talk will mainly focus on BI’s tech transfer concept, showing the whole engineering procedure from process science to production scale. Working with microbial expression systems often means dealing with very complex purification processes.
Achieving an efficient, fast and highly productive purification process within a short timeline requires an accurate communication strategy of process science and full scale production engineers. This cooperation follows well established documents
and meeting culture.
9:30 A Case Study: FlowVPE for Inline Analytics during Protein A Column Purification of Monoclonal Antibody
Ramsey Shanbaky, Senior Product Engineer, C Technologies, Inc
FlowVPE was used for real-time concentration measurements during Protein A chromatography process. Total mass loaded and total mass during breakthrough were determined. The elution profile was generated and total integrated mass determined. Integrated
mass values from the FlowVPE at each stage were compared to offline HPLC analysis.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Tales from the Crypt: The Hidden Consequences of Cell Death on Downstream Processing
Pete Gagnon, MSc, President and CSO, Validated Biosystems
This presentation will show the most damaging species of host cell proteins consisting of mixed covalent and non-covalent associations among chromatin remnants and misfolded proteins including product-related impurities. It will trace their development
from normal living cell metabolism, through apoptosis, secondary necrosis, and continuing in cell culture supernatants. It will highlight the primary mechanisms by which they interfere with purification methods and finally touch on methods
for suspending their adverse effects.
11:15 Use of Activated Carbon as an Adsorbent in the Polishing Step
Romas Skudas, Ph.D., Senior Scientist, Chromatography, Biopharm Process Solutions, Merck
We will present case studies showing flow-through purification results in the effective separation of HCPs, antibody fragments and LMW substances from post Protein A affinity capture solutions. In most cases, the mAb recovery was >85% and HCP
amount was reduced to <10ppm. This technology can be adapted to standard and new purification templates while maintaining critical product quality attributes and could enable fully continuous operation by linking the different flow through
chromatography media to form a single integrated system.
11:45 Optimize Host Cell Protein Reduction in Downstream Processes with the Aid of LC-MS Technique
Yinying Tao, Ph.D., Senior Research Scientist, Eli Lilly
12:15 pm Enjoy Lunch on Your Own
1:15 Dessert Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing
1:55 Close of Conference