THE Industry Meeting Place to Exchange Real-World Solutions to Improve Speed, Cost and Quality
Conference: October 26-29, 2015 · Exhibition: October 17-19, 2015 ·
Recovery & Purification
Recovery & Purification
Recovery & Purification
Building on the momentum being gained from the innovation of methodologies, materials science and technologies, companies will describe progress being made to optimize efficiencies, process design and flexibility in downstream processing for an emerging wave of antibodies and novel modalities.
Registration and Coffee
Marc Bisschops, Ph.D., Principal Scientist, Continuous Processing, Pall Life Sciences
Implementation of Continuous Processing
Case StudyNew DataData Based Comparison of Capture and Polishing Steps in a Continuous mAb Process
Multiple capture and polishing resins were characterized and optimized for batch manufacturing. Selected resins were characterized using a two column continuous manufacturing system. Optimized batch and continuous processes were compared for productivity, impurity, and quality measures. Data were used to compare the two manufacturing methods and determine the feasibility of continuous downstream manufacturing from the perspective of small development organization.
John Schreffler, Ph.D., Group Leader, Purification Process Development, Eisai
Overcoming Downstream Bottlenecks in Downstream Processing
Improved manufacturing processes are being developed to improve manufacturing network productivity and enable process fit into existing plants. Several technologies were evaluated to address these bottlenecks and help productivity including (i) newer generation protein A resins with higher binding capacity (ii) a semi-continuous mode of chromatography (sequential multi-column chromatography) for antibody capture on protein A, and (iii) single pass tangential flow filtration coupled to purification steps to enable in-line concentration of intermediate product streams. This presentation will show how integration of these process improvements into the purification process can facilitate debottlenecking and improve facility fit.
Lynn Conley, Ph.D., Senior Principal Scientist, Biogen
Productivity and Economic Advantages of Coupling Single-Pass Tangential Flow Filtration to Multi-Column Chromatography for Continuous Processing
Mark Schofield, Ph.D., Principal R&D Engineer, Applications R&D, Pall Life Sciences
New DataOperational Strategies and Buffer Design for Enabling Continuous/Straight Through Downstream Processing
Natraj Ram, Ph.D., Associate Director, Purification, Manufacturing Sciences, AbbVie Inc.
Networking Refreshment Break
Innovation at the Interfaces with R&D, The Harvest Step, and Formulations
Improved Methods for Assessing Developability of Monoclonal Antibody Candidates Prior to Purification
Peter Tessier, Ph.D., Associate Professor, Chemical & Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute
Monoclonal Flocculation with Smart Polymer for Efficient Clarification of High Titer Cell and Improved Removal of Impurities
Ken Kang, Ph.D., Principal Scientist, Head of Purification R&R, BioProcess Sciences, Eli Lilly and Company
New DataMedia Development Towards High Cell Density, High Productivity, and Low Perfusion Rates for Continuous Biomanufacturing Platforms
The presentation will discuss our systematic approach for developing a cell culture media to support very high cell densities and high productivities while maintaining low perfusion rates for the integrated continuous biomanufacturing platform.
Yang Yang, Ph.D., Staff Scientist I, Commercial Cell Culture Development, Sanofi
Concurrent Technology Workshops
Case StudyOptimal and Consistent Protein Glycosylation in Biosimilar Production
In the development of biosimilars, the biopharmaceutical industry is challenged with driving product quality toward equivalence with the innovative biotherapeutic. The consistent glycoform profile of biosimilars produced through large-scale cell culture is an important criterion that can dictate biological efficacy and ultimately regulatory approval. In addition, there is an increased interest in enhancing cell densities and product yields. This presentation will review advancements in glycosylation control in mammalian cell culture obtained through optimizing basal media, feeds, and process parameters. Case studies discussing recent optimization work utilizing the HyClone™ Metabolic Pathway Design process to, not only, improve product qualities, such as increased afucosylation or tri- and tetra-sialylated glycans, but also to increase cell density and enhance protein productivity, will be presented.
William G. Whitford, Senior Manager, Cell Culture, GE Healthcare
CQA Impurity Monitoring for Integrated Bioprocessing
This contribution proposes a novel approach using direct measurements of Critical Quality Attributes (CQA). We propose a CQA analyzer, which is based on a HPLC principle combined monolithic columns, which is used horizontally along the entire process, from upstream to downstream processing. Together with advanced multivariate data analysis algorithms, the chromatogram can be used as a fingerprinting method, allowing to track host cell impurities CQAs in a timely controlled way. Hence we present a PAT tool as per original definition.
Dr. Christoph Herwig, Professor of Biochemical Engineering, Vienna University of Technology, Austria
Abhinav A. Shukla, Ph.D., Vice President, Process Development & Manufacturing, KBI Biopharma, Inc.
Novel Approaches for Non-Chromatographic Purification of Proteins
Elastin-like Polyeptide Fusions for Purification and Delivery of Biologics
Ashutosh Chilkoti, Ph.D., Professor and Chair, Department of Biomedical Engineering, Duke University
Case StudyNew DataA Universal Non-Affinity Purification Platform for Toxicity and Phase I Trials
This presentation will describe an approach to IgG purification that merges 3 growing trends in the industry. Pre-emptive removal of chromatin, which is known to interfere with all purification methods. Increasing reliance on flow-through chromatography, in this case describing a hybrid approach that increases productivity and purification performance. Polishing with a simulated-moving-bed (SMB) -based method that further increases productivity. Biosimilar case studies will illustrate all new data.
Pete Gagnon, M.S., Group Manager, Downstream Processing, Bioprocessing Technology Institute, Singapore
The Future of Cell Therapy
Anthony Davies, Ph.D., President, Dark Horse Consulting
Short Break to Move to Keynote Session
Innovating mAb Production to Support the Immunotherapy Revolution
A new paradigm in cancer therapy is emerging with the recent success of the antibody mediated, immune tumor killing response for melanoma. Evaluations have expanded to include a range of tumor types. In addition new alternatives and combinations are aimed at improving patient non responsiveness to PD-1. These foundational efforts of emerging cancer treatment need to be supported by agile antibody supply solutions that meet the capacity demands, while improving global access and lowering costs. Technology solutions have been implemented to speed process development and shorten the critical time to first in human clinical studies. Innovative approaches towards the 'process of the future' will be shown that support flexible multi product lower cost manufacturing. Continuous processing enabled by single use provides an integrated solution and the implementation challenges will be discussed.
David J. Pollard, Ph.D., Executive Director, BioProcess Development, Merck & Co. Inc.
Innovative Process Development Strategies to Drive the Rapid Clinical Introduction of Emerging Biologics
The movement of a large portfolio, consisting of a broad spectrum of biological molecule-modalities, requires seamless integration from the research bench to the clinic. Deep alignment and partnership between the Research and the Process/Analytics functions allows for rapid and systematic product candidate screening, eliminating the most problematic candidates. Combining state-of-the-art cell lines with a regimented application of robust high-throughput process and analytical development packages enables record speeds to the first patient with minimal resources.
Spencer Fisk, Global Head, Biologics Process R&D, Novartis Pharma AG, Switzerland
Novel Approach to Developing and Producing Human Experimental Vaccines for HIV
Michael Anthony (Tony) Moody, M.D., Chief Medical Officer, Associate Professor of Pediatrics, Duke Human
Trick or Treat! Halloween Reception and Exposition Hall Grand Opening
The opening night reception sponsored by Roche will feature a Halloween theme complete with a fun and festive ambiance. Come and enjoy Halloween-inspired food, drinks, decorations and games while networking with exhibitors, poster presenters and other attendees in the exposition hall.
Registration and Coffee
Amgen's Next-Generation Biomanufacturing Facility
Described here is the establishment of a biomanufacturing platform for the production of biologic medicines. Competitive product portfolios that can respond quickly to changes in market dynamics have necessitated optimization of production strategies. The "Next-Generation Biomanufacturing" platform allows for fast and flexible drug operations for synthesis of drug substance in a reconfigurable manufacturing system. Key enabling technologies include modular construction, single-use bioreactors, disposable plastic containers, continuous purification processing and real-time quality analysis. Amgen's Next-Generation Biomanufacturing changes the way we will manufacture in the 21st Century.
Kimball Hall, Vice President Manufacturing, Amgen Singapore Manufacturing Pte. Ltd.
What is the Future of Continuous Processing - What is the Time Frame for Implementing Fully Continuous Processing in Commercial Production?
Konstantin Konstantinov, Ph.D., Vice President, Technology Development, Genzyme
Uwe Gottschalk, Ph.D., Chief Technology Officer, Pharma Biotech, Lonza, Switzerland
Improvements in Rapid, High-Throughput Process Development
Case StudyNew DataThe Use of a Scalable High-Throughput Method to Characterize and Optimize the PEGylation of a Recombinant E.coli Derived Enzyme
Development of a lysine PEGylation step was performed using high throughput methods to enable rapid screening of process parameters and identification of critical process parameters. This method using a statistical DOE approach was found to be accurate, repeatable, and scalable making it a useful development and characterization tool.
Christopher Miller, Senior Process Development Scientist, Downstream Process Development, KBI Biopharma
New DataHigh Throughput Methods to Streamline Process Development and Improve Process Understanding
This presentation will highlight several areas of process development where our group has implemented high throughput chromatography screening techniques: 1) resin pipette tips to support upstream candidate selection, 2) early phase downstream development screening using resin slurry plates to map parameters and miniature columns to assess process robustness and 3) miniature columns for process characterization of late stage candidates.
John Welsh, Associate Principal Scientist, Process Development and Engineering, Merck & Co.
Case StudyNew DataHigh Throughput Process Development to Accelerate Speed to the Clinic for Antibodies
Gregory A. Barker, Ph.D., Senior Engineer, Biologics Process Development, Bristol-Myers Squibb
Concurrent Technology Workshops
Case StudySingle-Use Fermentation: Understanding Process Economy and Process Performance
The entry of single-use bioprocessing and the benefits that come with disposables have generated interest in the microbial community. This talk will present results from a process economy comparison of fermentation scenarios based on stainless steel and single-use equipment. Additionally, data will be shown from a wet-work study of an E.coli domain antibody production using stainless steel and disposable equipment.
Kenneth Clapp, Senior Global Product Manager, Bioreactors, GE Healthcare
An Insight into Recent Developments in Protein A Chromatography
Protein A-based chromatography is the primary method used to purify MAbs. There has been a significant development of protein A chromatography media (resin), giving both higher capacity and improved stability to meet the changing requirements of the industry. More improvements are to come. We will provide some insights into the future plans of GE Healthcare's Life Sciences business for protein A media and our thoughts on what will be needed for the next generation of products.
Jonathan Royce, Senior Product Manager, Bioprocess Product Marketing - Downstream, GE Healthcare
Case StudyNew DataComparison of Methods and Materials for Single Use Bag Extractable Testing
This study highlights the relationship between two extractable test methods and the materials of construction of single use bag systems. The data show that the BioPhorum Operations Group (BPOG) protocol may not be sufficient as a single method for detecting extractables from single use bag systems, and that use of advanced materials like fluoropolymers allows more robust extractable detection methods.
Mike W. Johnson, Global Bioprocess Applications Manager for Life Sciences, Entegris, Inc
Networking Luncheon in the Exposition Hall
Thomas C. Ransohoff, Vice President & Principal Consultant, BioProcess Technology Consultants, Inc.
Challenges and Impact of Emerging Modalities and Expression Systems on Downstream Processing
Case StudyNew DataDemonstration of a Consistent and Robust Process for a Novel VLP-Peptide Conjugate Vaccine
Jennifer Thorn, Ph.D., Associate Research Fellow, Pfizer
Case StudyNew DataUse of Mechanistic Modeling to Improve Process Understanding and Control of Polishing Chromatography Steps for Fc-Fusion Proteins
This work employs mechanistic chromatography modeling to gain improved understanding and control of column behaviors using fundamental adsorption and transport measurements. Cases will be presented to illustrate model-based evaluation of closely-related process parameters, as well as comparison between simulated and experimental results. Furthermore, in silico experimentation can facilitate efficient development and characterization of purification processes.
Xuankuo Xu, Ph.D., Senior Scientist, Biologics Process Development, Bristol-Myers Squibb
New DataDownstream Processing Challenges Associated with the Purification of BMPs Expressed in Mammalian Systems
Bioventus LLC is developing an engineered BMP with enhanced receptor affinity optimized for increased efficacy in patients. The production of BMPs offers unique challenges not normally associated with conventional biologics such as antibodies. Challenges include the low solubility at physiological pH and a tendency to aggregate and precipitate requiring unusual conditions to stabilize the molecule throughout the production process. The presentation will focus on the development of processes to overcome production challenges unique to BMP family members.
Christopher T. Brown, M.S., Program Manager, Early Stage Protein Manufacturing, Bioventus LLC
Advances in Host Cell Protein Identification, Understanding and Clearance
Case StudyNew DataCharacterization of Host-Cell Proteins Using Mass Spectrometry Enables Effective Purification Optimization
Host-cell proteins (HCP) belong to in-process impurities of biopharmaceuticals and can pose challenges to development of an optimized downstream purification process. Identification and quantitation of HCPs using mass spectrometry-based workflow enhanced the understanding of HCPs in terms of their physical properties and potential interaction with the biopharmaceutical proteins, which provide valuable information for optimization of purification process.
Lin Zang, Ph.D., Senior Scientist, Analytical Development, Biogen
New DataA Novel Approach to Monitor Clearance of Host Cell Proteins Associated with Monoclonal Antibodies
Min Zhu, Ph.D., Senior Scientist/Purification Process Sciences, MedImmune LLC
Identification of Individual Host Cell Proteins with Mass Spec - Top Down and Bottom Up Approaches
Paul Brown, Ph.D., Scientist, Pfizer Inc.
Bioprocess "Problem-Solving" Discussion Topics and ModeratorsThese moderated discussions on a variety of bioprocess topics will allow you to share strategies and brainstorm solutions in an informal, small group setting.
Carsten Voss, Ph.D., Applications Specialist, Process Chromatography, Bio-Rad Laboratories GmbH, Germany
Novel Chromatography Selectivities and Innovation in Materials Science for Next Generation Purification
Antibody Unfolding/Aggregation on Macroporous and Polymer Grafted Cation Exchange Resins
Giorgio Carta, Ph.D., Lawrence R. Quarles Professor, Department of Chemical Engineering, University of Virginia
A Comparison of Multimodal Chromatographic Resins: Protein Binding and Selectivity
Incorporation of multimodal resins at large-scale has steadily increased due to their ability to provide enhanced selectivity as compared to ion exchangers and hydrophobic interaction chromatography resins. Here we describe a high throughput method for identifying optimal operating conditions in terms of pH and salt concentration for multiple mixed mode resins in a single set of experiments using low material volumes. The insights gained from this work are then used to compare the selectivity of multimodal resins and resulting product yield to one another. Moreover, the assessment of multiple proteins enables the identification of the best mixed mode resin for a particular class of proteins.
Leslie Wolfe, Ph.D., Senior Scientist, Downstream Process Development, KBI Biopharma
New DataNovel Approaches to Modulating Product Quality of Monoclonal Antibodies
Natraj Ram, Ph.D., Associate Director, Purification, Manufacturing Sciences, AbbVie Inc.
New DataSeparation of IgG Glycoforms and Subclasses Using Fc Gamma Receptors as Affinity Ligands
Austin Boesch, M.S., Co-Founder, Chief Executive Officer, Zepteon, Inc.
Improving Yield, Purity, Control, and Product Quality Attributes in Downstream Processing
Unlocking the Power of Analytics in Support of QbD in Process Development
In preparation for commercialization, Regeneron typically introduces a new high titer cell line and optimized production process. For this work, the principles of Quality by Design is leveraged for targeted, rational development. The presentation will provide examples of how analytical support is applied to serve a persistent focus on critical quality attributes to drive this development effort.
Hanne Bak, Ph.D., Senior Director, Purification Development, Regeneron Pharmaceuticals, Inc.
New DataAt-Line Process Analytical Technology (PAT) for Feed-Forward Control and More Efficient Scale Up of Biopharmaceutical Microfiltration Unit Operations
We present a novel approach to de-risk MF scale-up through the use of process analytical technology (PAT). Chromatography based PAT was employed to improve the consistency of an MF step that had been a bottleneck in the process used to manufacture a recombinant protein. A 10 minute reverse phase ultra high performance liquid chromatography (RP-UPLC) assay was developed to provide at-line monitoring of protein concentration. The method was successfully validated and method performance was comparable to previously validated methods. The PAT tool revealed areas of divergence from a mass balance based model, highlighting specific opportunities for process improvement. Adjustment of appropriate process controls led to improved operability and significantly increased yield, providing a unique example of successful PAT deployment in the downstream purification of a recombinant protein. The general approach presented here should be broadly applicable to reduce risk during scale-up of filtration processes and should be suitable for feed-forward and feed-back process control.
Douglas Watson, Ph.D., Senior Process Engineer, Merck Manufacturing Division, Merck & Co., Inc.
Case StudyNew DataA Unique Approach to Limit Aggregates in Final Purified Products
Veronique Bailly, Ph.D., Principal Scientist, BioProcess Development CMC, Team Lead, BioProcess Development CMC, Biogen
Networking Luncheon and Last Chance for Exposition Hall Viewing
Sigma S. Mostafa, Ph.D., Director, Process Development, KBI Biopharma Inc.
Innovation at the Interface with Formulations
New DataImpact of Ion-mAb Interactions on the UFDF Process: Towards Process and Product Design
Diane D. Dong, Ph.D., Principal Scientist, Manufacturing Sciences, AbbVie
Challenges of High Concentration Formulations - Dealing with Viscosity and Excipients
Pfizer Representative (Invited)
Networking Refreshment Break
Improving Process Performance in Clinical and Commercial Manufacturing
Case StudyNew DataHydrophobic Interaction Chromatography (HIC) Step Process Improvement in a Legacy Recombinant Human Enzyme Manufacturing Process
First generation legacy biologics manufacturing processes typically suffer from lack of thorough process characterization work and process understanding. The process improvement initiatives are further constrained due to the associated regulatory and validation impact of any process changes. In this work we present a case study of how the HIC capture step in a recombinant human enzyme (rhEnzyme) manufacturing process was improved and optimized within the bounds of the existing regulatory filings and process definitions. The process improvements led to substantially higher step yields, debottlenecking of the manufacturing process and improvement in overall processing efficiency. Understanding the impact of chromatography resin variability on process performance was key to the success of the process improvement project. The process knowledge was established via in-house data mining and analysis, lab-scale experimentation, manufacturing investigations and discussions with the resin vendor.
Rohit Ingale, Ph.D., Process Engineer III, Manufacturing Sciences and Technology (MSAT), Genzyme, a Sanofi Company
Downsizing Downstream Processing: A Novel Single-Use Purification Platform for Biologics
Upstream advancements have increased the volumetric productivity of cell culture processes thereby enabling the single-use upstream platform. Downstream operations remain dominated by column chromatography, a technology that has experienced relatively marginal increases in productivity, creating a mismatch with upstream technology. While traditional columns provide excellent chromatographic performance, the process productivity disadvantages inherent in this technology have created a roadblock to the overall modernization of biomanufacturing. A new platform of single-use (per batch) chromatography employs traditional, proven chromatography chemistries in a hydrogel membrane format that enables resin-like capacity with high speed flow characteristics typical of membranes. The combination of these performance attributes allows dramatically downsized and simplified process devices, which in turn, enables very simple, compact, flexible, yet robust downstream operations. This talk will describe capture and polish applications across a variety of modalities, including strong anion exchange and mixed-mode chemistries, and highlight some exceptional performance data, including expanded viral clearance.
James Stout, Ph.D., Vice President, Process Sciences, Natrix Separations, Inc.
Data Mining Full Scale Production Data for Continuous Process Validation
Brian Kearns, Ph.D., Principal Scientist, Technical Support, Manufacturing Sciences, Eli Lilly and Company
Close of Conference