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Key Sessions

Jorg Thommes

Biomanufacturing Has Matured from a Key Enabler to a Value Driver, So What’s Next?

Visterra Inc.

Niklas Engler

Future Strategies for Bioprocessing

F. Hoffmann-La Roche

Showing of Streams
10:00 - 10:45

Morning Coffee and Poster Tour 1

Showing of Streams
12:20 - 13:35

Lunch in the Exhibition Hall and Live Labs

Showing of Streams
15:50 - 16:30

Afternoon Coffee and Poster Tour Two

Showing of Streams
17:30 - 17:35
End of BPI 2018

End of BPI 2018

08:20 - 08:30 10 mins
Viral Safety
Chairperson's Opening Remarks
08:30 - 09:30 60 mins
Viral Safety
Ask the Regulators – Regulatory Breakfast Briefing
  • Arifa Khan - Senior Investigator, FDA/CBER
  • Albert Stühler - Deputy Head, Virus Safety, Paul-Ehrlich-Institut
more

In this hour-long session, delegates will be given the opportunity to pre-submit questions which will then be posed to the regulators and key leaders in the industry. Topics covered historically include:

  • Strategies and considerations for viral safety and raw materials
  • ATMP considerations
  • Cell bank testing and in vitro vs. in vivo assays
  • European clinical trials guidelines and requirements for IMPs from human blood origin
  • Viral safety requirements and orphan drug status
  • Risk assessment and viral safety retroviral safety margin according to ICH Q5A
  • Viral clearance studies and quality standards
  • NGS
08:50 - 09:00 10 mins
Cell Culture and Upstream Process Development
Chairperson's Opening Remarks
08:50 - 09:00 10 mins
Downstream Processing
Chairperson's Opening Remarks
08:50 - 09:00 10 mins
Continuous Processing
Chairperson's Opening Remarks
08:50 - 09:00 10 mins
Bioprocess Analytics and Control Strategies
Chairperson's Opening Remarks
08:50 - 09:00 10 mins
Vaccines
Chairperson's Opening Remarks
08:50 - 09:00 10 mins
Cell Line Development & Engineering
Chairperson's Opening Remarks
08:50 - 09:00 10 mins
Industry 4.0
Chairperson's Opening Remarks
09:00 - 09:30 30 mins
Cell Culture and Upstream Process Development
Biomanufacturing Has Matured from a Key Enabler to a Value Driver, So What’s Next?
  • Jorg Thommes - Senior Vice President Pharmaceutical Sciences & Technology, Visterra Inc.
more

Productivity and operational reliability of recombinant protein and antibody manufacturing have matured to an extent that Drug Substance manufacturing could almost be considered commoditizes. However, there new frontiers in biomanufacturing that will need substantial technology development. In this presentation, we will discuss emerging needs in biomanufacturing, e.g. further industrialization of antibody manufacturing (buzzword Industry 4.0), accelerated manufacturing for early clinical testing, and manufacturing for new therapeutic modalities.

09:00 - 09:30 30 mins
Downstream Processing
Biomanufacturing Has Matured from a Key Enabler to a Value Driver, So What’s Next?
  • Jorg Thommes - Senior Vice President Pharmaceutical Sciences & Technology, Visterra Inc.
more

Productivity and operational reliability of recombinant protein and antibody manufacturing have matured to an extent that Drug Substance manufacturing could almost be considered commoditizes. However, there new frontiers in biomanufacturing that will need substantial technology development. In this presentation, we will discuss emerging needs in biomanufacturing, e.g. further industrialization of antibody manufacturing (buzzword Industry 4.0), accelerated manufacturing for early clinical testing, and manufacturing for new therapeutic modalities.

09:00 - 09:30 30 mins
Continuous Processing
Cell Line Selection Challenges for a Perfusion Based Process: Case Study of a Non Antibody Molecule
  • Arna Andrews - Director, Cell Line Development, CSL Limited
more

This presentation will describe a case study which highlights the challenges with the screening and selection of cell lines destined for a perfusion process of a complex non antibody molecule.

These challenges include the lack of a representative small scale perfusion system for clone screening and the inability of standard shake flask stability studies to identify stability issues.

09:00 - 09:30 30 mins
Bioprocess Analytics and Control Strategies
Biomanufacturing Has Matured from a Key Enabler to a Value Driver, So What’s Next?
  • Jorg Thommes - Senior Vice President Pharmaceutical Sciences & Technology, Visterra Inc.
more

Productivity and operational reliability of recombinant protein and antibody manufacturing have matured to an extent that Drug Substance manufacturing could almost be considered commoditizes. However, there new frontiers in biomanufacturing that will need substantial technology development. In this presentation, we will discuss emerging needs in biomanufacturing, e.g. further industrialization of antibody manufacturing (buzzword Industry 4.0), accelerated manufacturing for early clinical testing, and manufacturing for new therapeutic modalitie

09:00 - 09:30 30 mins
Vaccines
Biomanufacturing Has Matured from a Key Enabler to a Value Driver, So What’s Next?
  • Jorg Thommes - Senior Vice President Pharmaceutical Sciences & Technology, Visterra Inc.
more

Productivity and operational reliability of recombinant protein and antibody manufacturing have matured to an extent that Drug Substance manufacturing could almost be considered commoditizes. However, there new frontiers in biomanufacturing that will need substantial technology development. In this presentation, we will discuss emerging needs in biomanufacturing, e.g. further industrialization of antibody manufacturing (buzzword Industry 4.0), accelerated manufacturing for early clinical testing, and manufacturing for new therapeutic modalitie

09:00 - 09:30 30 mins
Cell Line Development & Engineering
Cell Line Selection Challenges for a Perfusion Based Process: Case Study of a Non Antibody Molecule
  • Arna Andrews - Director, Cell Line Development, CSL Limited
more

This presentation will describe a case study which highlights the challenges with the screening and selection of cell lines destined for a perfusion process of a complex non antibody molecule.

These challenges include the lack of a representative small scale perfusion system for clone screening and the inability of standard shake flask stability studies to identify stability issues.

09:00 - 09:30 30 mins
Industry 4.0
Biomanufacturing Has Matured from a Key Enabler to a Value Driver, So What’s Next?
  • Jorg Thommes - Senior Vice President Pharmaceutical Sciences & Technology, Visterra Inc.
more

Productivity and operational reliability of recombinant protein and antibody manufacturing have matured to an extent that Drug Substance manufacturing could almost be considered commoditizes. However, there new frontiers in biomanufacturing that will need substantial technology development. In this presentation, we will discuss emerging needs in biomanufacturing, e.g. further industrialization of antibody manufacturing (buzzword Industry 4.0), accelerated manufacturing for early clinical testing, and manufacturing for new therapeutic modalities.

09:30 - 10:00 30 mins
Cell Culture and Upstream Process Development
Future Strategies for Bioprocessing
  • Niklas Engler - Head Technical Development Biologics Europe, VP, F. Hoffmann-La Roche
more
09:30 - 10:00 30 mins
Downstream Processing
Future Strategies for Bioprocessing
  • Niklas Engler - Head Technical Development Biologics Europe, VP, F. Hoffmann-La Roche
more
09:30 - 10:00 30 mins
Continuous Processing
A Comparison of Different Clonal Phenotypes in Perfusion CHO Cell Culture
  • Jean-Marc Bielser - Scientist, Merck KGaA
more

Merck KGaA is following the global trend of continuous manufacturing. To support perfusion cell culture development, small-scale semi-continuous screening methods were developed. These methods were applied on a set of different clones and compared to real continuous conditions (lab-scale bioreactors). Growth and productivity performance were compared and helped to define a ranking strategy for screening application, specific to perfusion.

09:30 - 10:00 30 mins
Bioprocess Analytics and Control Strategies
Future Strategies for Bioprocessing
  • Niklas Engler - Head Technical Development Biologics Europe, VP, F. Hoffmann-La Roche
more
09:30 - 10:00 30 mins
Vaccines
Future Strategies for Bioprocessing
  • Niklas Engler - Head Technical Development Biologics Europe, VP, F. Hoffmann-La Roche
more
09:30 - 10:00 30 mins
Viral Safety
Spotlight Presentation: A Representative from Asahi Kasei
09:30 - 10:00 30 mins
Cell Line Development & Engineering
A Comparison of Different Clonal Phenotypes in Perfusion CHO Cell Culture
  • Jean-Marc Bielser - Scientist, Merck KGaA
more

Merck KGaA is following the global trend of continuous manufacturing. To support perfusion cell culture development, small-scale semi-continuous screening methods were developed. These methods were applied on a set of different clones and compared to real continuous conditions (lab-scale bioreactors). Growth and productivity performance were compared and helped to define a ranking strategy for screening application, specific to perfusion.

09:30 - 10:00 30 mins
Industry 4.0
Future Strategies for Bioprocessing
  • Niklas Engler - Head Technical Development Biologics Europe, VP, F. Hoffmann-La Roche
more
10:00 - 10:45 45 mins
Morning Coffee and Poster Tour 1
10:45 - 10:50 5 mins
Cell Culture and Upstream Process Development
Chairperson's Opening Remarks
  • Swanpil Bhargava - Seattle Genetics, USA, Director and Department Head, BioProcess Development
more
10:45 - 11:15 30 mins
Downstream Processing
Innovative Purification Techniques and Downstream Process Development for Next Generation Therapeutics
  • David O'Connell - Lecturer in Biotherapeutics, School of Biomolecular & Biomedical Science, University College Dublin
more
10:45 - 11:05 20 mins
Continuous Processing
Model Based Control Strategies: Enabling Continuous Upstream Biomanufacturing for Antibody Production
  • Christoph Herwig - Head Biochemical Engineering, Institute of Chemical Engineering, TU Wien, Austria
more

Process robustness is the key industrial need in bioprocesses. However variability in raw materials as well as due to biological nature call for tools to identify, monitor and control process variations along the process chain. The current contribution wants to motivate solutions of mechanistic model development, PAT solutions and data science solutions for enabling upstream manufacturing robustness of bioprocesses. The following elements will be covered for example:

• Workflows how goal driven mechanistic models can be developed

•Models as PAT tool: Demonstrations of cases in which models are solutions to measure less

•Multiparametric control and event prediction

We will show case studies in which tunable promoter systems along with model based control techniques were successfully deployed to enable robust upstream processing to enable robust downstream processing. This solution will pave the ways to continuous biomanufacturing.

Take Home Message:

Models can be set up by process developers. Model based tools are available to allow robust upstream processing for robust downstreaming. This full interpretation of PAT is the key enabler for continuous biomanufacturing.

10:45 - 11:05 20 mins
Bioprocess Analytics and Control Strategies
Model Based Control Strategies: Enabling Continuous Upstream Biomanufacturing for Antibody Production
  • Christoph Herwig - Head Biochemical Engineering, Institute of Chemical Engineering, TU Wien, Austria
more

Process robustness is the key industrial need in bioprocesses. However variability in raw materials as well as due to biological nature call for tools to identify, monitor and control process variations along the process chain. The current contribution wants to motivate solutions of mechanistic model development, PAT solutions and data science solutions for enabling upstream manufacturing robustness of bioprocesses. The following elements will be covered for example:

• Workflows how goal driven mechanistic models can be developed

•Models as PAT tool: Demonstrations of cases in which models are solutions to measure less

•Multiparametric control and event prediction

We will show case studies in which tunable promoter systems along with model based control techniques were successfully deployed to enable robust upstream processing to enable robust downstream processing. This solution will pave the ways to continuous biomanufacturing.

Take Home Message:

Models can be set up by process developers. Model based tools are available to allow robust upstream processing for robust downstreaming. This full interpretation of PAT is the key enabler for continuous biomanufacturing.

10:45 - 11:15 30 mins
Vaccines
Adventures in Securing FDA Approval of a Novel Cell Line and Influenza Vaccine
  • Dan Adams - Executive Chairman and Global Head of Business Development, Protein Sciences Corporation, USA
more

Protein Sciences invented Flublok® influenza vaccine, the first approved recombinant flu vaccine, and its expresSF+® insect cell line and secured FDA approval in 2013. However, none of this was easy or straightforward.  This talk will focus on the difficulties encountered in overcoming the FDA’s concerns about a novel cell line, adventures in scale up in multiple countries, the problems developing companies encounter in marketing a novel flu vaccine and the prospects for such companies to succeed in this field.

10:45 - 11:15 30 mins
Viral Safety
Lessons from the CAACB on the Prevention and Control of Adventitious Agent Contamination
  • Paul W. Barrone - Associate Director BioMAN & CAACB, MIT Center for Biomedical Innovation
more

Adventitious agent contamination of cell culture-based biomanufacturing operations for the production of protein and monoclonal antibody biotherapeutics are infrequent, but when they do occur, they are very costly, impact manufacturing operations, and can potentially impact patient safety and product supply. To support the biopharmaceutical manufacturing industry the Consortium on Adventitious Agent Contamination (CAACB) at MIT have conducted a number of projects with the goal of identifying best practices in the control and prevention of adventitious agent contamination. These projects include collecting data on industry wide viral contamination experience, collecting data on the effectiveness of media treatment technologies, and identification of industry wide facility segregation approach. This presentation will highlight the key lessons that the CAACB has learned from its current activities.

10:45 - 11:15 30 mins
Cell Line Development & Engineering
Data Driven CLD – Translation of Big Data Information to Enhance Cell Line Selection and Host Cell Engineering
  • Christine DeMaria - Director, Cell Line Development, Sanofi
more
10:50 - 11:20 30 mins
Cell Culture and Upstream Process Development
Investigating the Change in a Charge Variant Profile of a Monoclonal Antibody from a Large-Scale Mammalian Cell Culture Process
  • Jurgen Van de Lagemaat - Principal Scientist/Product Steward, MSD, The Netherlands
more

An elevated level of a charge variant was observed in the drug substance of large-scale manufacturing batches of a monoclonal antibody. To elucidate the upstream processing variables causing the shift in the charge variant profile, an extensive root cause investigation was performed.

A qualified 3-L bioreactor scale-down model, representative of the large-scale manufacturing cell culture process, was used to study the impacts of the most potential root causes. Reduced peptide mapping LC-MS analysis was performed to characterize the various charge variant peak fractions analytically. In addition, mapping of the charge distribution over time during the cell culture process was performed to develop a mechanistic understanding of the pathway for C- and N-terminal modifications of the antibody during the cell culture.

This presentation provides a holistic overview of the investigation including the small-scale bioreactor experimentation and underlying mechanistic studies performed to understand root cause. Mitigation strategies to minimize variability in charge variant profile and to increase process robustness during large-scale production will be discussed.

11:05 - 11:25 20 mins
Continuous Processing
PAT Applications in Batch and Conti Biotech Processes
  • Jens Traenkle - Head of PAT Special Applications Biomolecules, Bayer AG, Germany
more
  • Single-use PAT applications
  • Bringing the lab to the process: automation of at-line analytical instruments (data integration and physical integration)
  • Developing PAT for cQAs
  • Towards future process control
11:05 - 11:25 20 mins
Bioprocess Analytics and Control Strategies
PAT Applications in Batch and Conti Biotech Processes
  • Jens Traenkle - Head of PAT Special Applications Biomolecules, Bayer AG, Germany
more
  • Single-use PAT applications
  • Bringing the lab to the process: automation of at-line analytical instruments (data integration and physical integration)
  • Developing PAT for cQAs
  • Towards future process control
11:15 - 11:45 30 mins
Downstream Processing
Systematic Use of Statistical DoE and In Silico Modeling to Reduce Experimentation during DSP Development: A Vaccine Case Study
  • Beckley Kungah Nfor - Scientist, Janssen Vaccines & Prevention B.V., The Netherlands
more

The production of safe and efficacious vaccines at low cost is essential to guarantee world-wide vaccine availability and affordability, especially in developing countries. Our proprietary PER.C6® cell line and PIN platform technologies have enabled the expression and production of viral vaccines at very high titers in cell cultures, thereby shifting the opportunities for further cost reduction to the downstream process (DSP). To reduce experimental workload needed for DSP development, a systematic approach involving the combined use of statistical DoE and in silico process modeling is proposed. This is exemplified by way of a case study involving the optimization of a chromatographic step for purification of a viral vaccine from PER.C6® derived cell culture harvest. The optimization problem involved four experimental factors (column load, flow rate, upper cut point, virus strain) and two outputs (virus purity and yield). The main objectives of the study were to define a design space satisfying all design constraints, and to define a higher operating column load (within the design space) so as to reduce column and buffer footprints (cost). Through the combined use of statistical DoE and in silico modeling, it was possible to achieve the set objectives with much fewer experiments than would have been needed with a purely DoE approach.

11:15 - 11:45 30 mins
Vaccines
Systematic Use of Statistical DoE and In Silico Modeling to Reduce Experimentation during DSP Development: A Vaccine Case Study
  • Beckley Kungah Nfor - Scientist, Janssen Vaccines & Prevention B.V., The Netherlands
more

The production of safe and efficacious vaccines at low cost is essential to guarantee world-wide vaccine availability and affordability, especially in developing countries. Our proprietary PER.C6® cell line and PIN platform technologies have enabled the expression and production of viral vaccines at very high titers in cell cultures, thereby shifting the opportunities for further cost reduction to the downstream process (DSP). To reduce experimental workload needed for DSP development, a systematic approach involving the combined use of statistical DoE and in silico process modeling is proposed. This is exemplified by way of a case study involving the optimization of a chromatographic step for purification of a viral vaccine from PER.C6® derived cell culture harvest. The optimization problem involved four experimental factors (column load, flow rate, upper cut point, virus strain) and two outputs (virus purity and yield). The main objectives of the study were to define a design space satisfying all design constraints, and to define a higher operating column load (within the design space) so as to reduce column and buffer footprints (cost). Through the combined use of statistical DoE and in silico modeling, it was possible to achieve the set objectives with much fewer experiments than would have been needed with a purely DoE approach.

11:15 - 11:45 30 mins
Viral Safety
Harmonisation of Viral Segregation Strategy for Manufacturing Network with Multiple Facility Designs and Production Scales
  • Bonnie Shum - Engineer II, Global Biologics Manufacturing Sciences and Technology (MSAT), Genentech, a member of the Roche Group
more

Virus contamination of biologics may arise from contaminated raw materials as well as cross contamination of product intermediates, and risk mitigation such as appropriate viral segregation at manufacturing facilities is essential.  With complex manufacturing networks that consist of multiple facility configurations and production scales, a harmonized viral segregation strategy that accounts for these differences is required to support network flexibility. Pre- and post-viral steps can be challenging to define as viral clearance is a continuum throughout the purification process and reliant on multiple process steps. Given diversity in facility designs and differences in the process step order and viral clearance claims, the development of a network strategy should focus on operational controls, procedural controls, and the demonstration of viral inactivation of cleaning and sanitization.  The presentation will focus on the development of the network-aligned viral segregation strategy at Roche/Genentech to defend viral segregation by the incorporation of regulatory requirements, feedback from across the manufacturing network, and risk-based touch-point analysis.

11:15 - 11:45 30 mins
Cell Line Development & Engineering
Product Quality Control Strategy during Cell Line Development for Non-mAb Complex Modalities
  • Zhimei Du - Head Cell Line Development, Merck Research Labs
more

New product-related impurities have been found to accompany non-mAb complex modalities, which usually don’t exist in standard mAb production. Many of these PQAs are related to protein folding and assembly efficiency inside the cell, which impact post-translational modifications directly or indirectly. Our presentation will illustrate the importance of selecting appropriate cell/upstream conditions through screening and/or engineering, as part of quality control strategy to obtain the desired recombinant protein PQA profile.

11:25 - 11:45 20 mins
Continuous Processing
Digitalisation Platform and Supervisory Control of A Continuous Integrated Bioprocess Using Raman Spectroscopy
  • Fabian Feidl - PhD Student, Morbidelli-Group, Institute for Chemical and Bioengineering, ETH, Zurich, Switzerland
more

The presentation uses the highly complex continuous integrated bioprocesses to show the potential of digital solutions for online process monitoring and control. A particular focus will be put on the different technological solutions which have to be integrated into a digital process system including IT platforms, process model solutions as well as advanced online sensors.

11:25 - 11:45 20 mins
Bioprocess Analytics and Control Strategies
Digitalisation Platform and Supervisory Control of A Continuous Integrated Bioprocess Using Raman Spectroscopy
  • Fabian Feidl - PhD Student, Morbidelli-Group, Institute for Chemical and Bioengineering, ETH, Zurich, Switzerland
more

The presentation uses the highly complex continuous integrated bioprocesses to show the potential of digital solutions for online process monitoring and control. A particular focus will be put on the different technological solutions which have to be integrated into a digital process system including IT platforms, process model solutions as well as advanced online sensors.

11:45 - 12:15 30 mins
Downstream Processing
Spotlight Presentation: A Representative from GE Healthcare
11:45 - 12:15 30 mins
Continuous Processing
Scale-up of Continuous Multicolumn Chromatography for the Protein A Capture Step: from Bench to Clinical Manufacturing
  • Ozan Ötes - Process Engineer, Sanofi-Aventis Deutschland GmbH – On behalf of Pall Biotech
more

Continuous downstream processing is gaining a lot of momentum. Continuous multicolumn chromatography is a key enabler, promising significant advantages. The use of the Cadence BioSMB Process system has been evaluated for clinical scale purification of a monoclonal antibody. In this presentation, we will present data supporting scale up from laboratory scale to large scale manufacturing. The presentation will also cover data for a longer manufacturing campaign based on a perfusion upstream process. The performance of the process scale system has been evaluated for product quality attributes and impurity removal, as well as process consistency, thereby also addressing some of the regulatory aspects of continuous multicolumn chromatography.

The presentation will also address process economical considerations for the use of continuous multicolumn chromatography in clinical manufacturing.

11:45 - 12:15 30 mins
Vaccines
Spotlight Presentation: A Representative from Sartorius
11:45 - 12:15 30 mins
Viral Safety
Spotlight Presentation: A Representative from Charles River
11:45 - 12:15 30 mins
Cell Line Development & Engineering
Spotlight Presentation: A Representative from Thermo Fisher Scientific
11:45 - 12:15 30 mins
Industry 4.0
Industry 4.0 Spotlight Presentation - A Representative from Synthace
11:50 - 12:20 30 mins
Cell Culture and Upstream Process Development
Spotlight Presentation: A Representative from CMC Biologics
12:20 - 13:35 75 mins
Lunch in the Exhibition Hall and Live Labs
13:35 - 14:05 30 mins
Cell Culture and Upstream Process Development
Automated fed batch fermentation screening platform and data handling
  • Daniela Reinisch - Director, Upstream Development, Biopharmaceuticals Process Science (Microbials), Boehringer Ingelheim, Austria
more
  • Fermentation screening of microbial host strains at 15 mL scale
  • Fully automated feeding and online sampling
  • Ensure reproducibility in larger scales – saving time and resources
  • Data structure, storage and visualization for effective process development
13:35 - 14:05 30 mins
Downstream Processing
Applicability of UV Spectroscopy for At-Line Aggregation Monitoring in Downstream Processing
  • Apoorva Alva - Investigator, GlaxoSmithKline
more

The implementation of Process Analytical Technology (PAT) tools within a downstream purification process would offer key benefits, enabling continuous real or near real time quality data to be obtained, allowing a level of process characterization and control that is currently not feasible. This would minimize the time and effort required for process optimization and improve process robustness, whilst still allowing the understanding of the process to be further developed. UV spectroscopic techniques have desirable attributes for bioprocess monitoring as they are non-invasive and do not consume the analyte. This presentation, through the use of various case studies, will provide an overview of the work done in investigating the use of UV absorption spectra in conjunction with Partial Least Square (PLS) modelling to generate predictive models for protein aggregation, that can be implemented for process analysis and control.

13:35 - 14:05 30 mins
Continuous Processing
Feedback on the DiViNe Project – Vaccine Purification by Affinity Chromatography
  • Manuel Carrondo - Professor of Chemical and Biochemical Engineering, FCT-UNL Vice-President,, iBET Portugal
more
13:35 - 14:05 30 mins
Bioprocess Analytics and Control Strategies
Applicability of UV Spectroscopy for At-Line Aggregation Monitoring in Downstream Processing
  • Apoorva Alva - Investigator, GlaxoSmithKline
more

The implementation of Process Analytical Technology (PAT) tools within a downstream purification process would offer key benefits, enabling continuous real or near real time quality data to be obtained, allowing a level of process characterization and control that is currently not feasible. This would minimize the time and effort required for process optimization and improve process robustness, whilst still allowing the understanding of the process to be further developed. UV spectroscopic techniques have desirable attributes for bioprocess monitoring as they are non-invasive and do not consume the analyte. This presentation, through the use of various case studies, will provide an overview of the work done in investigating the use of UV absorption spectra in conjunction with Partial Least Square (PLS) modelling to generate predictive models for protein aggregation, that can be implemented for process analysis and control.

13:35 - 14:05 30 mins
Vaccines
Feedback on the DiViNe Project – Vaccine Purification by Affinity Chromatography
  • Manuel Carrondo - Professor of Chemical and Biochemical Engineering, FCT-UNL Vice-President,, iBET Portugal
more
13:35 - 14:05 30 mins
Viral Safety
Approach to Pre- and Post-Viral Filtration Room Segregation
  • Serge Monpoeho - Director of Virology, Regeneron Pharmaceuticals
more

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.
13:35 - 13:50 15 mins
Cell Line Development & Engineering
Whole Genome Sequencing to Study Genetic Changes in Stable CHO Cell Lines
  • Alexandre Regamey - Director, Molecular Biology, Selexis
more

CHO cells are the most frequently applied host-cell system for the industrial manufacturing of recombinant protein therapeutics. The rapid generation and identification of high-producing clones that do not lose their expression capability over time is a major focus of the industry. The use of cytogenetic analysis with next-generation sequencing (NGS) combined to the proprietary bioinformatic tool SUREscan™, allows us to analyze the whole genome of any generated cell line, improving monoclonality assessment and traceability of RCBs. We will show that our CHO-M cell line is chromosomally stable indicating that the SUREtechnology Platform™ generates RCBs with chromosomally stable lineages.

13:50 - 14:20 30 mins
Cell Line Development & Engineering
Fed-Batch Cell Culture in Ambr15 – Scalability & Applications
  • Jolanda Gerritsen - Expert Technology, CLD, Genmab B.V.
more
14:05 - 14:35 30 mins
Cell Culture and Upstream Process Development
Spotlight Presentation: A Representative from Thermo Fisher Scientific
14:05 - 14:35 30 mins
Downstream Processing
Corynex®: A Gram-Positive Microbial Protein Secretion System for cGMP Biologics Production
  • Yoshimi Kikuchi - Executive Professional and Associate General Manager, Ajinomoto Co., Inc., Japan
more

Corynex® is a novel microbial protein secretion system using gram-positive Corynebacterium glutamicum, which has been used for the industrial production of amino acids. Recently, a biologics candidate developed by a global pharmaceutical company and manufactured at Ajinomoto Althea using Corynex®, has entered phase I clinical trials.

14:05 - 14:35 30 mins
Continuous Processing
Spotlight presentation
14:05 - 14:35 30 mins
Bioprocess Analytics and Control Strategies
Bioprocess Development in the Age of Digitalisation: Intelligent Experiments as Key Component
  • Nicolas Cruz-Bournazou - PhD, Technische Universität Berlin
more

Advances in digitalisation bring a large number of possibilities to create, collect, store, and share data. This has a significant impact in biotechnology were the complexity of living organisms can be studied deeper and analysed by computers and experiments can be carried out by robotic stations fast and in a high degree of parallelization. Nevertheless, speaking of automation, control, and digitalization, the bioindustry is clearly behind other fields of engineering. The complexity of biological systems hampers an efficient use of computer aided tools. The substantial problem is that it is not possible to create a reliable mathematical model (digital twin) even of simple biological systems.  Changes in protein expression, metabolic activity, mutations, etc. cannot be foreseen, described, nor fully understood. This means that the internet of things in biotechnology will be always coupled with experimental activities to validate and re-adjust models to living systems.

These experiments need to be designed intelligently and carried out in miniaturized parallel Liquid Handling Stations (LHS). Existing engineering tools need to be further developed and adapted to fill this gap between the digital space and the experimental system. Methods for Design of Experiments (DoE) have been developed and widely applied to this end. Still, if we consider systems where the time dependent response is important (e.g. most engineering applications) the experimental design has to consider the nonlinear dynamics of the process. If this is the case, more advanced tools are required, namely methods for Optimal Experimental Design (OED). These methods have to be further developed aiming to i) design optimal dynamic experiments in very short time, ii) communicate with the robotic facility that preforms the experiment, iii) learn from the data as it is being generated, iv) re-fit the parameters of the model to the data, and v) re-design the optimal experimental strategy.

All these methods need to be integrated in a framework to create an intelligent laboratory for rapid characterization of biosystems including: easy interaction of all devices, experimental design programs tailored for robotic LHS, online optimization algorithms that enable an optimal operation of the robots, and advanced control methods to assure the correct operation of the facilities.

14:05 - 14:35 30 mins
Vaccines
Spotlight presentation
14:05 - 14:35 30 mins
Viral Safety
Alternative Approaches to Viral Segregation in Facility Design and Operation
  • Kavita Ramalingam Iyer - Associate Director, Merck Sharp & Dohme
more

Viral safety is a key quality in biopharmaceuticals manufacturing. Sufficient virus clearance usually rests on the cumulative effect from different purification steps. A cumulative effect can only be obtained provided that segregation control measures are in place.

Viral segregation control measures implemented by industry often do not commensurate with the associated risk they seek to mitigate. Consequentially this may lead to complex facility design with disproportionate control measures. In addition to impacting speed of valuable medicines to patients, the approach has detrimental impact on capital and operating costs as well as making facilities less flexible and adaptable – counter to the direction the industry needs to take. Factors to this scenario include influence of historical internal practices, company procedures and guidance, perceived risk of regulatory approval and sub optimal health agency guidance documents. There is consensus within industry and health agency that where technology has improved with regards to protecting the product from contamination, regulations control measures have not moved in step.

Following the principles of Risk Management approaches as espoused in EU GMP Annex 2 and ICH guidance, the BPOG Closed systems team proposes methods to facility segregation that are alternative to conventionally applied methods of physical barriers and engineering controls (e.g. walls and dedicated AHU’s).  These alternative methods include use of closed systems along with procedural and temporal controls, as determined by the risk assessment of the process. The acceptability of these methods will be demonstrated via case studies.

The presentation will also elaborate on how these measures can lead to an expansion of interpretation and application of the current health agency regulations pertaining to Viral Safety.  Consequently, this would bring them inline with current technological advancements and understanding.

The benefit of this approach is a risk based method that allows organisations to simplify future facility design, ensuring high quality product enters the market in a timely manner and upholding patient safety.

Key Objectives

  • Share Risk based approaches aligned with regulatory guidance, and their use for a rational, simplified facility design
  • Identification of key areas for implementing contamination prevention measures
  • Discuss use of system closure as a means for viral segregation purposes, reducing footprint and complexity compared with traditional approaches such as physical separation by walls.
14:05 - 14:35 30 mins
Industry 4.0
Bioprocess Development in the Age of Digitalisation: Intelligent Experiments as Key Component
  • Nicolas Cruz-Bournazou - PhD, Technische Universität Berlin
more

Advances in digitalisation bring a large number of possibilities to create, collect, store, and share data. This has a significant impact in biotechnology were the complexity of living organisms can be studied deeper and analysed by computers and experiments can be carried out by robotic stations fast and in a high degree of parallelization. Nevertheless, speaking of automation, control, and digitalization, the bioindustry is clearly behind other fields of engineering. The complexity of biological systems hampers an efficient use of computer aided tools. The substantial problem is that it is not possible to create a reliable mathematical model (digital twin) even of simple biological systems.  Changes in protein expression, metabolic activity, mutations, etc. cannot be foreseen, described, nor fully understood. This means that the internet of things in biotechnology will be always coupled with experimental activities to validate and re-adjust models to living systems.

These experiments need to be designed intelligently and carried out in miniaturized parallel Liquid Handling Stations (LHS). Existing engineering tools need to be further developed and adapted to fill this gap between the digital space and the experimental system. Methods for Design of Experiments (DoE) have been developed and widely applied to this end. Still, if we consider systems where the time dependent response is important (e.g. most engineering applications) the experimental design has to consider the nonlinear dynamics of the process. If this is the case, more advanced tools are required, namely methods for Optimal Experimental Design (OED). These methods have to be further developed aiming to i) design optimal dynamic experiments in very short time, ii) communicate with the robotic facility that preforms the experiment, iii) learn from the data as it is being generated, iv) re-fit the parameters of the model to the data, and v) re-design the optimal experimental strategy.

All these methods need to be integrated in a framework to create an intelligent laboratory for rapid characterization of biosystems including: easy interaction of all devices, experimental design programs tailored for robotic LHS, online optimization algorithms that enable an optimal operation of the robots, and advanced control methods to assure the correct operation of the facilities.

14:20 - 14:50 30 mins
Cell Line Development & Engineering
High Stringency Selection of High Producer CHO Cells Using a Metabolic Selection Marker
  • Mark Trautwein - Senior Scientist, Bayer AG - Pharmaceuticals Division
more

The concept of high stringency selection of cells producing high amounts of a desired protein of interest is well known in the art and different solutions exist. However, many existing solutions exhibit different drawbacks e.g. need to engineer a host cell line or use of an antibiotic. The presentation will introduce a high stringency selection system using an endogenous metabolic selection marker without the need for cell line engineering.

14:35 - 15:05 30 mins
Cell Culture and Upstream Process Development
Big Data and Decision Processes to Ensure More Stability and Less Risk in USP
  • Michael Sokolov - Postdoctoral Fellow and Lecturer, ETH Zurich
more
  • Platforms for data storage and analysis
  • Visualisation of this
  • How is this data used to improve processes?
  • Adding value to the process through the data
14:35 - 15:05 30 mins
Downstream Processing
From Batch to Integrated, to Automated Integrated Biologics DSP
  • A Member - of the, UK Continuous Integrated Biologics Manufacturing Consortium
more

A UK-based consortium has been initiated to apply an automated integrated system to the downstream processing of different biologics. A description of the automation strategy will be presented along with case study data of a mAb process and the process development decisions made in transferring from a traditional single-use batch process to a single-use continuous integrated process.

14:35 - 15:05 30 mins
Continuous Processing
From Batch to Integrated, to Automated Integrated Biologics DSP
  • A Member - of the, UK Continuous Integrated Biologics Manufacturing Consortium
more

A UK-based consortium has been initiated to apply an automated integrated system to the downstream processing of different biologics. A description of the automation strategy will be presented along with case study data of a mAb process and the process development decisions made in transferring from a traditional single-use batch process to a single-use continuous integrated process.

14:35 - 15:05 30 mins
Bioprocess Analytics and Control Strategies
Enhanced Process Control and Process Monitoring for Consistent Produce Quality and Improved Manufacturing Efficiency
  • Susan O'Brien - Process Analytics Leader, Manufacturing Sciences and Technology, BioMarin Pharmaceutical Inc.
more
14:35 - 15:05 30 mins
Vaccines
New approaches for characterization of genetic stability of vaccine cell lines
  • Ali Azizi - Senior Scientist, Analytical Research and Development, North America, Sanofi Pasteur, USA
more

Genetic mutations that occur during cell passaging in a bioreactor can lead to a heterogeneous population. These new mutations may impact product production and quality where small sub- populations could potentially overtake the initial cell culture, resulting in a final cell population that is different from the starting pool. For vaccine manufacturers, occurrence of mutations during cell culturing poses a risk to the use of recombinant proteins. The evaluation of gene copy numbers by a qPCR method is one of the common approaches used to assess the consistency of cell lines. However, due to several challenges including amplification efficiency differences that were apparent between these reference standards and test samples, two new approaches (Digital PCR and High throughput sequencing) were developed in our platform. The developed methods were able to overcome the challenges associated with the conventional methods such as qPCR. These technologies have been successfully used to characterize the genetic stability of cell lines including transgenic cell lines.

14:35 - 15:05 30 mins
Viral Safety
Characteristics of virus assay systems for viral clearance studies: the use of PCR and / or infectivity methods
  • Maria Farcet - Manager, Global Pathogen Safety, Shire, Austria
more
  • Regulatory requirements/expectations – infectivity may be preferred, but PCR sometimes necessary
  • Virus models with low/no infectivity, or complex infectivity assays (e.g. HEV, B19V)
  • Combined mode of virus reduction: Ab-mediated NF enhancement, removal and inactivation during column chromatography
  • Points to consider with PCR
  • Virus stock preparations: nucleic acid content, infectivity vs. PCR titres
  • Method design: what is / is not detected?
  • Multi-spiked study runs: a possibility?
14:35 - 15:05 30 mins
Industry 4.0
Enhanced Process Control and Process Monitoring for Consistent Produce Quality and Improved Manufacturing Efficiency
  • Susan O'Brien - Process Analytics Leader, Manufacturing Sciences and Technology, BioMarin Pharmaceutical Inc.
more
14:50 - 15:20 30 mins
Cell Line Development & Engineering
Application of Automation for Cell Line Screening and Clone Selection
  • Jennitte Stevens - Director, Amgen
more
15:05 - 15:35 30 mins
Cell Culture and Upstream Process Development
Spotlight Presentation: A Representative from Applikon
15:05 - 15:35 30 mins
Downstream Processing
Spotlight Presentation: A Representative from PendoTech
15:05 - 15:35 30 mins
Continuous Processing
Industry-Wide and US Government Sponsored Initiative for Steady-State Manufacturing of Biologics using Continuous Countercurrent Tangential Chromatography (CCTC)
  • Oleg Shinkazh - Founder & CEO, ChromaTan Corporation
  • Hans Johansson - Application Manager, Life Sciences, Purolite
more

CCTC is a new column-free continuous purification platform for mAbs, vaccines and other biologics, providing a single-use alternative to column chromatography. Recent multi-million dollar awards from government agencies enabled the development of a new vision for  Integrated End-To-End Continuous Bioprocessing using CCTC. Chromatan and partner Purolite will share new data from multiple evaluations of CCTC for various chromatographic modalities, and present a new resin that was jointly developed specifically to increase the productivity of the CCTC platform.

15:05 - 15:35 30 mins
Bioprocess Analytics and Control Strategies
GlycanAssure™ Software version 2.0
  • Dennis Nagtalon - Sr. Manager, Global SW Product Management, Pharma Analytics, Thermo Fisher Scientific
more

The Applied Biosystems™ GlycanAssure™ Glycan Analysis and Quantitation System is the first glycan analysis platform that combines both high throughput and high data quality, and offers an integrated glycan analysis platform that helps save labor, time, and cost of analysis.

The GlycanAssure Software is easy-to-use data acquisition and analysis software for glycans with security, auditing, and E-signature (SAE) features. It breaks new ground in user-friendly navigation with an intuitive dashboard design, highly visible buttons for common operations, easy-to-read graphical displays to monitor the state of consumables, simplified plate setup, and a handy maintenance scheduling calendar functionality.

GlycanAssure Data Analysis software allows quick viewing of analyzed and un-analyzed glycan samples and quick comparison of different analysis methods. It includes built-in primary analysis with quality control, so you can make decisions about the quality of data as it is produced without the need to transfer output files to other software.

GlycanAssure Software has a full suite of security, auditing, and E-signature features to help enable 21 CFR part 11 compliance.

15:05 - 15:35 30 mins
Vaccines
Spotlight presentation
15:05 - 15:35 30 mins
Viral Safety
Spotlight Presentation: A Representative from SGS
15:05 - 15:35 30 mins
Industry 4.0
GlycanAssure™ Software Version 2.0
  • Dennis Nagtalon - Sr. Manager, Global SW Product Management, Pharma Analytics, Thermo Fisher Scientific
more

The Applied Biosystems™ GlycanAssure™ Glycan Analysis and Quantitation System is the first glycan analysis platform that combines both high throughput and high data quality, and offers an integrated glycan analysis platform that helps save labor, time, and cost of analysis.

The GlycanAssure Software is easy-to-use data acquisition and analysis software for glycans with security, auditing, and E-signature (SAE) features. It breaks new ground in user-friendly navigation with an intuitive dashboard design, highly visible buttons for common operations, easy-to-read graphical displays to monitor the state of consumables, simplified plate setup, and a handy maintenance scheduling calendar functionality.

GlycanAssure Data Analysis software allows quick viewing of analyzed and un-analyzed glycan samples and quick comparison of different analysis methods. It includes built-in primary analysis with quality control, so you can make decisions about the quality of data as it is produced without the need to transfer output files to other software.

GlycanAssure Software has a full suite of security, auditing, and E-signature features to help enable 21 CFR part 11 compliance.

15:20 - 15:50 30 mins
Cell Line Development & Engineering
Spotlight Presentation: A Representative from Sartorius
15:50 - 16:30 40 mins
Afternoon Coffee and Poster Tour Two
16:30 - 17:00 30 mins
Cell Culture and Upstream Process Development
Evaluation of Customer 40L SUB for both Seed Train and Inoculum Train
  • Edward Chan - Technical, Cell Culture Pilot Plant, Genetech, Inc
more

The Cell Culture Pilot Plant at Genentech in South San Francisco is a hybrid facility that uses both stainless steel and disposable bioreactors for CHO cell culture in Seed Train, Inoculum Train, and Production stages.  In the biotech industry, disposable rocker bioreactors have been used as Seed Train and Inoculum Train (N-4 to N-2) operations due to their efficient, cost effectiveness, and small footprint. In 2016, Cell Culture Pilot Plant evaluated a rocker bioreactor and found the rocker system did not have a robust pH and dO2 control for continuous Seed Train process that can run for up to 5 months. To address these challenges, Genentech and Thermo Fisher collaborated to modify a 30L Single Use Fermentor bag (SUF) to a 40L Single Use Bioreactor bag (SUB) that matches a traditional 20L stainless steel bioreactor to have robust pH and dO2 control.  As part of this evaluation, mass transfer and cell culture experiments were performed.  The presentation will be focusing on cell culture performance data, ongoing efforts to resolve equipment associated challenges, and expand the use of the 40L SUB in Inoculum Train.

16:30 - 17:00 30 mins
Downstream Processing
Continuous Low pH Viral Inactivation for mAb Production Processes
  • Laura David - Research Associate, Bayer/INVITE GmbH, Germany
more

As continuous processing using disposable equipment is gaining more and more importance, the application of continuous viral clearance within this new process environment needs to be evaluated. Continuous low pH viral inactivation was developed and implemented into the MoBiDiK PRO demonstration plant. In order to transfer the defined and tight residence time distribution from batch to continuous processing, the coiled flow inverter (CFI) was implemented. It allows robust operation while using disposable equipment in a compact design. Current achievements and future challenges will be discussed.

16:30 - 17:00 30 mins
Continuous Processing
Continuous Low pH Viral Inactivation for mAb Production Processes
  • Laura David - Research Associate, Bayer/INVITE GmbH, Germany
more

As continuous processing using disposable equipment is gaining more and more importance, the application of continuous viral clearance within this new process environment needs to be evaluated. Continuous low pH viral inactivation was developed and implemented into the MoBiDiK PRO demonstration plant. In order to transfer the defined and tight residence time distribution from batch to continuous processing, the coiled flow inverter (CFI) was implemented. It allows robust operation while using disposable equipment in a compact design. Current achievements and future challenges will be discussed.

16:30 - 17:00 30 mins
Vaccines
Aluminium Based Suspensions Vs. Liposomal
  • Martinus Capelle - Scientific Director, Head Formulation Science & Technology, Janssen Pharmaceutical Companies of Johnson & Johnson, The Netherlands
more
16:30 - 17:00 30 mins
Viral Safety
Continuous Low pH Viral Inactivation for mAb Production Processes
  • Laura David - Research Associate, Bayer/INVITE GmbH, Germany
more

As continuous processing using disposable equipment is gaining more and more importance, the application of continuous viral clearance within this new process environment needs to be evaluated. Continuous low pH viral inactivation was developed and implemented into the MoBiDiK PRO demonstration plant. In order to transfer the defined and tight residence time distribution from batch to continuous processing, the coiled flow inverter (CFI) was implemented. It allows robust operation while using disposable equipment in a compact design. Current achievements and future challenges will be discussed.

16:30 - 17:00 30 mins
Cell Line Development & Engineering
A Single Cycle Cell Line Approach
  • Pamela Pegman - Sr Principal Scientist, Cell Line Development, Biotherapeutics Pharm. Sci, Pfizer Inc
more

The ability to generate cell lines capable of supporting both early and late stage clinical as well as commercial programs requires a holistic cross-functional approach to assessing cell line suitability. By leveraging an integrated manufacturability assessment and cell line and process development platforms we have proposed such an approach. This presentation will focus on the strategies required to enable single cycle cell line development.

17:00 - 17:30 30 mins
Cell Culture and Upstream Process Development
Development of Concentrated Media Formulations and Compounding Strategies to Support Next Generation Cell Culture Processes
  • Sara Gall - Principal Engineer, Amgen, USA
more

The development of perfusion-based cell culture processes is shifting the scale of cell culture operations from bioreactors to media preparation tanks with perfusion feed rates that can exceed one vessel volume per day.  Frequent and high volume media preparations can create operational complexity and limit the overall facility run rate.  Multiple technical solutions exist to overcome these challenges.  This presentation will outline two potential solutions to facilitate high run rate, perfusion-based cell culture operations:  media concentrates and granulated media.

17:00 - 17:30 30 mins
Downstream Processing
Efficacy Studies Of An Inactivation Process Of A Flaviviridae
  • Cédric Charretier - Head of Downstream Processing Unit, Bioprocess R&D Europe, Sanofi Pasteur, France
  • Vincent Marin - Scientific Manager, Downstream Processing, Bioprocess R&D Europe, Sanofi Pasteur, France
more
17:00 - 17:30 30 mins
Continuous Processing
Opportunities for Implementing Continuous Concepts in Downstream Processing of Complex Therapeutic Proteins – Some Perspectives
  • Kumar Dhanasekharan - Head of Development and Tech Transfer, Amicus Therapeutics
more
  • Business drivers for complex glycoproteins
  • Challenges to implementation – When and how?
  • Manufacturing facility fit considerations
17:00 - 17:30 30 mins
Vaccines
Efficacy Studies Of An Inactivation Process Of A Flaviviridae
  • Cédric Charretier - Head of Downstream Processing Unit, Bioprocess R&D Europe, Sanofi Pasteur, France
  • Vincent Marin - Scientific Manager, Downstream Processing, Bioprocess R&D Europe, Sanofi Pasteur, France
more
17:00 - 17:30 30 mins
Viral Safety
Efficacy Studies Of An Inactivation Process Of A Flaviviridae
  • Cédric Charretier - Head of Downstream Processing Unit, Bioprocess R&D Europe, Sanofi Pasteur, France
  • Vincent Marin - Scientific Manager, Downstream Processing, Bioprocess R&D Europe, Sanofi Pasteur, France
more
17:00 - 17:30 30 mins
Cell Line Development & Engineering
Panel Discussion: Cell Line Manufacturability Assessment Strategies and Integration at the Interfaces
more
  • How to choose the best cell line for manufacturing in early screening?
  • Approaches to align workflows internally and improve the interface of USP and cell line development to select more adaptive clones
  • What type of cell line properties and performance criteria are required for bioprocessing?
  • Cell line and clone selection strategies for manufacturability
  • Integration of high throughput automation platforms to improve selection and screening
  • Evaluating how good small scale models are for modelling bioreactor conditions
  • Accurate clone screening and cell line selection using media formulations used in upstream processing
  • Methodologies for identifying product stability traits and product quality attributes for choosing cell line for manufacturing at early stages
17:30 - 17:35 5 mins
End of BPI 2018