The Waterside Conference


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Process Analysis & Automation

Chaired By:

Robert R. Boulanger, PhD
CRB
Barry Rosenblatt, PhD
SME Biotech Consulting

Topics

  • Artificial Intelligence
  • Sensors
  • Scale-Down Models
  • Product Comparability
  • In-Line, At-Line, Off-Line Analysis
  • Process Optimization
  • Integration of Unit Operations
  • Continuous Processing
  • In-Line Dilution
  • Process Automation
  • Single-Use Systems and Components

Expansion & Expression

Chaired By:

Blair McNeill, PhD
Alkermes plc
Swapnil Bhargava
Seattle Genetics, Inc.

Topics

  • Cloning and Performance Optimization
  • Media and Buffer Development
  • Single-Use Systems and Components
  • Closed Systems
  • Robotics
  • Perfusion, Fed Batch, Batch Processes
  • Feed and Harvest Strategies
  • Managing Metabolites and Dissolved Gases
  • In-Line, At-Line, Off-Line Analysis
  • Continuous Processing
  • Integrating Unit Operations
  • Defining Lots and Release Testing

Contaminant Control

Chaired By:

Jeri Ann Boose, PhD
Eurofins Lancaster Laboratories, Inc.
Raymond Nims, PhD
RMC Pharmaceutical Solutions, Inc.

Topics

  • Host Cell Proteins
  • DNA and Endotoxins
  • Sterility and Mycoplasma
  • Viral Contaminants and Clearance
  • Rapid Sterility Testing
  • Product Purity and Potency
  • Cell-Based Assays
  • Regulatory Expectations

Cell Line Development & Banking

Chaired By:

Alissa M. Resch, PhD
Coriell Institute for Medical Research
Fang Tian, PhD
American Type Culture Collection (ATCC)

Topics

  • Cell and Tissue Procurement
  • Cell Line History and Authentication
  • Informed Consent / Legal Issues
  • Cold Chain Management
  • Cell Bank Management
  • Stability and Characterization
  • Contaminant Identification and Clearance
  • Cryopreservation

Raw Materials & Contract Services

Chaired By:

Henry Lin, PhD
Boehringer Ingelheim Corporation
David Kolwyck, PhD
Biogen

Topics

  • Analytical Technologies for Raw Material Characterization
  • Raw Material Qualification
  • In-House Testing vs. Vendor CoA
  • Tech Transfer
  • Leveraging CDMO for Speed to Clinic
  • Vendor Qualification
  • Product Comparability
  • Use of Standards
  • Purity and Consistency
  • Acceptance Testing
  • Storage and Release Testing
  • Expired Materials

Featured Speakers

David Kolwyck
Director Materials Science, Biogen
Strategies to Monitor and Manage Raw Material Variability to Improve Process Consistency
Michael Washabaugh, PhD
Chief Scientific Officer, Adello Biologics
Todd L. Talarico, PhD
Vice President of Process Development, Medicago USA
Case Study: Investigation of a False Positive Result Encountered During Adventitious Agent Testing of a Novel Influenza Vaccine
Mark Berge
Principal Scientist, MedImmune, A member of the AstraZeneca Group
Understanding the Effect of Preparation Methods on Bioavailability of Components in a Cell Culture Feed
  • Abstract
    Medium and feed are key factors in the success of modern high titer cell culture processes. Ensuring that all vital nutrients are available when the cells need them is a critical part of developing a commercially viable large-scale production process. A key aspect of developing an upstream process is understanding the effects of scaling the unit operations and especially how the medium and feed is prepared. When the preparation methods at differing scales alter the availability of nutrients, the cell metabolism can be affected which alters cell growth, product titers, and even product quality. Recently, it has been discovered that the large-scale preparation method for a process feed is shown to have deleterious effects on its corresponding large-scale process. The most surprising discovery was that although one of the affected feed components was measurable at the expected concentration, it was not bioavailable to the cells. Details of the study and the resulting corrective actions will be discussed.
Gregory T. Bleck, PhD
Global Head of R&D, Biologics, Catalent Pharma Solutions, Inc.
Efficient Expression of Complex Proteins in Mammalian Cells
Maria M. Bednar, PhD
Scientist I, AT Virology, Biogen
Yves Durocher, PhD
Section Head, Mammalian Cell Expression - Human Health Therapeutics Research Center, National Research Council Canada
The Cumate-Inducible Switch for Stable CHO Pool and Clone Generation
  • Abstract
    We describe our cumate-inducible CHO expression platform for the rapid production of stable pool and clones for recombinant protein expression. The cumate-inducible system allows the generation of stable and scalable pools expressing high levels of monoclonal antibodies or r-proteins (>1 g/L) in 2–3 weeks post-transfection. The pools are also used to derive stable and high-expressing CHO clones for manufacturing therapeutic candidates. Herein, we show that the ability to regulate r-protein expression during pool generation confers an advantage for selecting high-producer cells. Reducing expression level (“off-state”) during the pool selection process dramatically enhances high-producer frequency compared to a pool in which expression was induced to high level (“on-state”), mimicking a constitutive expression system. This advantage is even more obvious when producing “difficult-to-express” r-proteins.
  • Biography
    Yves obtained his PhD in Biochemistry at the Université de Montréal in 1993. He joined the NRC in 1995 to work on the production of membrane receptors and recombinant proteins for various industrial partners involved in drug discovery projects. Yves manages a section of 33 members involved in protein expression and stable CHO cell line development for internal projects and external clients. His research activities focus on improving large-scale transient gene expression (LSTGE) platforms using HEK293 and CHO cells for protein production and on developing and engineering a stable CHO pool and clonal cell line platform for recombinant protein manufacturing. Yves is also an assistant professor at the Department of Biochemistry at the University of Montreal.
Barry Rosenblatt, PhD
President, SME Biotech Consulting
Development, Automation, and Qualification of Scale-Down Models for Protein Production and Purification
Stephen Stoltzfus
Principal Scientist / Group Leader, Viral Safety and Clearance Services, Eurofins Lancaster Laboratories, Inc.
Pitfalls of Viral Clearance Studies
Edita Botonjic-Sehic, PhD
Global Process Analytical Technology (PAT) Manager, Pall Life Sciences
Process Analytical Technology (PAT) for Continuous Bioprocessing
  • Abstract
    In recent years biotech companies have been emphasizing 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 in downstream processing of biotech products is to isolate the product of interest from the process stream that comes from the harvest unit operations and contains a variety of impurities. These impurities include product-related variants that might closely resemble the desired product and have an equivalent potency and safety profile. Spectroscopy is being proposed as an on-line PAT tool for continuous measurement of numerous critical quality attributes. In addition, real-time data collection will assist in the development of chemometric models used for predictive estimation of properties of a process and hence help in process analysis, optimization, monitoring, and control.
  • Biography
    Dr. Edita Botonjic-Sehic joined Pall Corporation in late 2016 and is currently Global Process Analytical Technology (PAT) Manager. In this role, she is responsible for the strategic conceptualization and implementation of process analytical technology (PAT) for the continuous bioprocessing portfolio. She brings more than 14 years of experience in spectroscopy and chemometrics for PAT and advanced analytical techniques to advancing this new concept. Prior to joining Pall Life Sciences, Dr. Botonjic-Sehic was a member of the PAT team within GlaxoSmithKline’s program for API development, and she also led a PAT team at TEVA Pharmaceuticals for drug product manufacturing, and was a principal investigator and program manager on several government-funded (DHS, TSWG, CTTSO) projects at Morpho Detection (formerly GE Homeland Security), where she specifically worked on the development of systems for trace and bulk materials detection. Dr. Botonjic-Sehic completed her PhD in Analytical Chemistry at the University of Rhode Island after undergraduate studies at Assumption College in both chemistry and mathematics. She is a respected leader in her field and an accomplished author of numerous papers, and frequently delivers talks in the field of spectroscopy and chemometrics.
John M. Baust, PhD
President, Founder, and Lead Scientist, CPSI Biotech
Strategies and Trends for Improving Sample Quality Following Cryopreservation
  • Biography
    John M. Baust, PhD is the Founder, President, and Lead Scientist of CPSI Biotech. Dr. Baust has 15+ years’ experience in research & medical device development and is a co-inventor on over 40 patents. Dr. Baust is a recognized innovator and entrepreneur in cryomedicine and is a pioneer in the area of molecular mechanisms of cell death and low temperature stress. Dr. Baust has published over 100 papers, reviews, book chapters, abstracts, and patents in the area of low temperature biology and has been instrumental in the advancement of the field of cryobiology into the molecular biological era focusing on signal transduction and apoptosis. In this regard, Dr. Baust is credited with the discovery of cryopreservation-induced delayed-onset cell death. In the area of research and technology development, Dr. Baust has led the development of numerous medical devices, including the Supercritical Nitrogen (SCN) and Pressurized Nitrogen (PSN) cryoablation devices for the treatment of cancer and cardiac arrhythmias. This is in addition to spearheading the development of the SmartThaw and SmartFreeze devices for improved cell and tissue cryopreservation. Coupled with these technical engineering developments, he leads life science research programs focused on the cell-molecular actions of cryoablation. These efforts have resulted in the identification of a significant molecular stress response component to freezing injury which is responsible for the differential sensitivity of various cancers to thermal ablation. In addition to these activities, Dr. Baust serves on the editorial boards of Biopreservation and Biobanking as well as Technology in Cancer Research and Treatment, and is a reviewer for several other scientific journals. Dr. Baust co-edited the book Advances in Biopreservation, is a past board member for the Society for Cryobiology, and currently serves on the Board and as Treasurer of the American College of Cryosurgery. Dr. Baust completed his studies at Cornell University, State University of New York at Binghamton, and Harvard Medical School.
Robert R. Boulanger, PhD
Process Specialist, CRB
Process Analysis and Automation
S. Steve Zhou, PhD
Director, Virology and Molecular Biology, MicroBioTest, div. of Microbac Laboratories, Inc.
Allen L. Burgenson
Global Subject Matter Expert – Testing Solutions, Lonza Walkersville, Inc.
Michael Brewer
Director, Pharmaceutical Analytics, Thermo Fisher Scientific
Detection of Adventitious Agents in CHO Cell Cultures Using Ultra-High Multiplex PCR and Next-Generation Sequencing
Serge Monpoeho, PhD
Sr. Director QC & Chief Virologist, Regeneron Pharmaceuticals, Inc.
Approach to Pre- and Post-Viral Clearance Room Segregation
  • Abstract
    Regeneron has been cited for a lack of physical barrier between pre- and post-viral clearance activities. In response to this regulatory observation, we committed to implementing improvements to further reduce any potential residual risk:
    • Closed System: A functionally closed system for the addition of post-viral step in-process solution
    • Temporal Segregation: A dedicated time sequence for assembly of equipment pre- and post-viral activities
    • Process and Personnel Segregation: A dedicated personnel flow path to restrict operators to specific operations to enhance process segregation
    • Material Segregation: The use of dedicated parts for pre- and post-viral clearance operations to further enhance process segregation
    • Environment Segregation: Dedicate specific drains for pre- and post-viral clearance activities
    • Physical Segregation: Due to space constraint, plant retrofitting was not feasible in this particular suite. However, new plant design includes physical segregation of pre- and post-viral clearance activities in downstream.
  • Biography
    Serge Monpoeho has a PhD in Virology. He currently assumes the position of Sr. Director in QC and Chief Virologist at Regeneron Pharmaceuticals in upstate New York. In his current function, Serge is responsible for some aspects of the QC Operation Support activities such as the product stability program as well as the virology program at the manufacturing site in Rensselaer. Before that Serge was in charge of the product viral safety program at Genentech in California for about 10 years.
Dayue Chen, PhD
Microbiology and Molecular Analytics, Bioprocess Research and Development, Eli Lilly & Company
MMV Inactivation by HTST: Beyond the Log10 Reduction Factors
  • Abstract
    This presentation will describe: 1) Why high temperature short time (HTST) is used in the biopharmaceutical industry for medium treatment; 2) The risk of mouse minute virus (MMV) contaminating cell culture bioreactors and the impact of such events; and 3) How to quantify the effectiveness of HTST treatment and the importance of GMP in reducing the risk of viral contaminations.
Balsam Shawky
Senior R&D Biologist, Cell Authentication, American Type Culture Collection (ATCC)
An Update on CO1 Multiplex PCR and Barcode Sequencing Analysis for Species Identification
Matthew Hammond
Senior Scientist, Amgen Inc.
Establishing an Attribute-Focused Approach to Raw Materials
Andreas Unsöld
Head of Cell Culture Media, Boehringer Ingelheim GmbH
Matthew Zustiak
Senior Scientist, Patheon, part of Thermo Fisher Scientific
Christopher W. Kemp, PhD
President, Kempbio, Inc.
Comparing Insect Culture and Mammalian Expression Systems
  • Abstract
    The transient expression of recombinant proteins in insect and mammalian cell-based systems is one of many critical factors driving growth in the field of biotechnology. The baculovirus expression vector system (BEVS) and plasmid-based mammalian cell transfection protocols have been refined to the point where the production of gram quantities of recombinant proteins is routine and timelines as short as 5–6 weeks starting from gene sequence are common. Each platform has its advantages and disadvantages related to productivity, protein stability and composition, process variability, timelines, and cost. This presentation will provide a comparison of the two platforms using examples of their use in the production of virus-like particles, protein complexes, and soluble proteins.
  • Biography
    Chris Kemp is President of Kempbio, Inc., a contract protein expression company located in Frederick, Maryland. Dr. Kemp has over 25 years of experience in the scale-up of recombinant protein expression systems including baculovirus, mammalian, and BacMam expression platforms. Chris founded the protein expression service company Kemp Biotechnologies, Inc. in 1992 and the molecular biology product company GeneChoice in 2000. The current company, Kempbio, was started in 2009 and is focused on rIgG expression, viral glycoprotein production and purification, and the production and purification of virus-like particles (VLPs).
Mark F. Witcher, PhD
Senior Specialist, Process Operations, Strategic Manufacturing Concept Group (SMCG), NNE
Successful Product Development – Yield, Purity, and Comparability: How Many Products Fail Phase III Clinicals
Because They are Not Comparable to the Product Designed and Tested Earlier?
Verne A. Luckow, PhD, JD
US Patent Attorney, The Intellectual Property Law Office of Verne A. Luckow, LLC
Morven McAlister, PhD
Sr. Technical Director, Regulatory and Validation Consultancy Group, Pall Life Sciences
Virus Filtration in Continuous Bioprocessing: Considerations for Filter Design Space and Validation
  • Abstract
    Continuous bioprocessing is rapidly gaining momentum, and seems likely to increase its role in manufacturing over the coming years. This is due to the benefits of operational flexibility and increased efficiency, product consistency, quality assurance, and significant cost savings. Implementing quality by design (QbD) principles and subsequent process validation into a continuous bioprocess poses a challenge, but also an opportunity to gain a robust process with assured drug quality. Viral safety assurance remains a critical aspect of bioprocessing of monoclonal antibodies (mAbs) and recombinant proteins. While robust virus clearance is well understood for batch processes, many questions remain on how to implement viral safety into continuous bioprocesses. For example, use of virus filtration in continuous bioprocessing is likely to involve low flow rates and significantly extended processing times compared to current batch applications. Applying QbD principles to understand the expected virus filter design space will be critical for successful implementation into continuous processing applications. Validation of viral filtration in continuous processing applications may also present new challenges. For example, careful consideration must be given to overcome potential virus viability issues or changes in the process fluid when testing for extended filtration times at low flow rates. Innovative test designs may be warranted to successfully validate virus filtration in continuous bioprocessing. Here we present data showing some process inputs that should be evaluated to determine critical control attributes for continuous bioprocessing applications. We also present data that show a robust virus filter design space is required for implementation into continuous bioprocessing applications. Specifically, our results show that high virus clearance can be achieved using worst-case test conditions to simulate virus filtration in a continuous bioprocess. Consideration is also given to the logistics of performing virus filtration over extended test durations.
  • Biography
    Morven McAlister received her BSc degree in Applied Microbiology from the University of Strathclyde (UK). Her PhD was completed at Queen's University of Belfast (UK) in the field of bioremediation. In 1999 she researched microbial contamination and biofilm formation in high purity water systems at the University of Arizona in Tucson. She joined Pall in 2001, and has held various technical leadership roles focused on microbial contamination control, specifically for sterile and virus filtration applications. She has extensive experience in filter validation, and her current focus involves applying quality by design (QbD) principles to optimize sterility assurance in batch and continuous bioprocessing applications.
Rosemary J. Versteegen, PhD
Chief Executive Officer, International Serum Industry Association
Marcin Łoś, PhD, DSc
Chief Executive Officer, Phage Consultants
Nikki Nogal, PhD
Senior Consultant Biologics Product Development, Latham BioPharm Group
Process Optimization after Commercialization
Antonio J. Scatena
Sr. Sales Representative, Gateway Analytical LLC
Marc G. Aucoin, PhD
Associate Professor, Center for Bioengineering and Biotechnology, University of Waterloo
UV Irradiation of High Absorbance Medium and its Utility as a Barrier Against Adventitious Agents in Fed-Batch Cultures
David A. Wareheim
Independent Consultant
Continuous Processing in Downstream Operations, In-Line Dilution, Chromatography, and Virus Filtration
Fang Tian, PhD
Lead Scientist, Cell Biology Group Leader, American Type Culture Collection (ATCC)
Sherri Dolan
Process Development Consultant, Sartorius Stedim Biotech
Kelvin G.M. Brockbank, PhD
CEO, Tissue Testing Technologies LLC
Steve Broach
Global Sales and Marketing Manager, LiCONiC Instruments
Dennis Binder
MilliporeSigma
New Molecules and Latest Cell Culture Media Production Technologies to Boost CHO Productivity, simplify Bioprocesses, and Ensure Batch-to-Batch Consistency
  • Abstract
    Industrial fed-batch cultivation of mammalian cells plays a key role in numerous therapeutic protein productions such as those of monoclonal antibodies. Next to high titers and product quality, a reliable and robust production process as well as process efficiency are main goals of the pharmaceutical industry. Here, new molecules and technologies that enhance CHO productivity and simultaneously simplify fed-batch processes will be presented. The modified amino acids O-Phospho-L-tyrosine and S-Sulfocysteine can be used in just one single neutral pH feed with higher room temperature stability, and thus bypass the well-known solubility and stability issues for conventional tyrosine and cysteine, respectively. Furthermore, the latest cell culture media (CCM) services that aim to ensure batch-to-batch consistency and enhance process efficiency will be disclosed. The recently launched impurity profiling allows tracking of several unintended impurities inherent in the CCM supply chain, thus ensuring that customers are fully aware of potential trace metal contaminants that influence final product quality. Finally, CCM compaction will be introduced as an expedient technology to significantly improve dry powder media (DPM) characteristics. The dry granulation of homogeneously milled DPM into compacted CCM usually comes with increased flowability, which leads to better handling and less dust formation, as well as an increased bulk density, resulting in lower storage and transport costs. Lastly, compacted CCM show an increased dissolution speed since the material sinks into the water instead of swimming on the water surface as observed for most uncompacted DPM, thus decreasing the risk of contamination as well as overall processing time.
Frank Romanski, PhD
Global Technical Marketing Manager, BASF Corporation
Donald L. Jarvis, PhD
President, GlycoBac LLC
Emily Schirmer
Director of Downstream Process Development, Catalent Pharma Solutions, Inc.