Cambridge Healthtech Institute’s 9th Annual
Bioproduction: Scale, Bioreactors & Disposables
Making It Work
August 14-15 , 2019
Cambridge Healthtech Institute’s “Bioproduction” conference reviews the finesse required to manufacture biologics including scale-down models, scaling up production, engineering bioreactors, single-use systems, and ensuring quality within
the context of increasing productivity; while ensuring safety and achieving reduced costs. A holistic review of bioprocessing will be explored, as well as practical details, such as monitoring and analyzing processes, and examining in detail
how bioreactors process cells and how to keep those cells happy. The conference will address robust production processes and next-generation technologies, while improving manufacturing platforms and ensuring product quality.
Final Agenda
Wednesday, August 14
6:00 - 6:45 am Seaport Fun Run/Walk (Seaport Hotel Plaza Lobby)
7:00 Registration Open and Morning Coffee
8:05 Chairperson’s Remarks
Jonathan Bones, PhD, Principal Investigator, Characterization and Comparability Laboratory, National Institute for Bioprocessing Research and Training (NIBRT)
8:15 KEYNOTE PRESENTATION:
Next-Generation Processes – Scaling Up or Scaling Out
Gregg Nyberg, PhD, Associate Vice President and Head, Biologics Process Development and Clinical Manufacturing, Merck & Co., Inc.
Right-sizing manufacturing capacity is a significant challenge for biopharmaceutical companies. Ever increasing pipeline diversity, unpredictable clinical results, and inaccurate market projections conspire to make long-range capacity planning an
exercise in frustration. This talk will discuss process and facility design strategies, which provide the flexibility needed to adapt to pipeline and demand changes.
9:00 FEATURED PRESENTATION: Technical Trends and Concepts in Modern Bioprocessing Facilities
Stefan Schmidt, PhD, MBA, COO and Head, Operations, BioAtrium AG
Currently many new bioprocessing facilities are planned, constructed and commissioned. This talk gives an overview on trends in facility design; how to implement hybrid or modular solutions, and how to embed digital strategies like automation, PAT approaches,
and paperless production already from the start. These concepts are explained through the example of a new commercial mammalian production plant.
9:30 Integrating PAT, Data Historian and Automation for Enhancing Process Understanding and Learning
Jean-François Hamel, PhD, Research Engineer, Chemical Engineering, Massachusetts Institute of Technology (MIT)
This study seeks to compare how well manual sampling compares with automated sampling in a cell culture bioreactor interfaced with in situ and at-line instruments, and connected to a data historian by OPC. All samples
are analyzed for the same analytes (e.g., substrates and metabolic products) and a correlation has been established between the two sampling procedures.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)
10:45 Process CO2 and Medium Ion Balance Control Strategy for Control of Galactosylation and Lactate Metabolism
Woo Suk Ahn, PhD, Scientist Upstream, Process Science, Global Manufacturing Science and Technology (MSAT), Sanofi US
The product quality of biologics can be affected by process conditions, medium components, and cell metabolism. We demonstrate the modulation of product quality through controlling pCO2 and medium ion balances. The pCO2 control strategy
and the prediction model by first principles lead to the switch of lactate metabolism from production to consumption mode, which was found to correlate to galactosylation.
11:15 Development of an In-House Cell Free Extract Process and Robotic Platform for Expression Optimisation
Michael
Anyadiegwu, PhD, Senior Scientist, Centre for Process Innovation Limited
Use of cell-free protein expression in bioprocessing has traditionally been limited by low yields and high cost. To address these issues, we herein describe the development of a scalable lysate generation process, used in tandem with a high-throughput
robotic screening method, as a platform for optimisation of cell-free expression, to support the development of robust and cost-effective cell-free manufacturing processes.
11:45 Scale Up Capabilities of
Single-Use Vessels for Cell Culture from Small to Pilot Scale
Michelet Dorceus,
Bioprocess Senior Field Applications Specialist, Eppendorf
Substituting traditional glass bioreactors with single-use equipment can greatly simplify the bioprocess workflow eliminating the need for cleaning and autoclaving. We will discuss the scalability of single-use vessels from small to pilot scale,
using CHO, where a peak cell density of approximately 12 million cells/mL, with a viability above 95%.
12:00 pm Robust Scale-Up, Critical
Process Parameter Identification and Reduction of Validation Batches Required
in the Biopharmaceutical Industry through CFD Modelling and Statistical
Modelling (MVDA) Analysis
Jamie McCarry, Process
Development Engineer II, Engineering, APC Ltd.
As the biopharmaceutical industry moves towards single use systems, traditional scale-up techniques are becoming less applicable. Large variation is observed in vessel performance due to the bespoke nature of systems increasing the difficulty of scale-up.
Companies have reduced the scale factor from lab to pilot plant to final production in an effort to overcome these scaling issues. An accurate characterisation of unique vessels allowed the most appropriate scale-up strategy to be identified and tested
in CFD. The critical process parameters for scale-up were identified using MVDA analysis of lab scale experiments to scale accurately to pilot plant. This combination of CFD and MVDA working in parallel reduced the number of validation batches required
during scale-up from laboratory to pilot plant scale.
12:15 Enjoy Lunch on Your Own
1:00 Dessert Break in the Exhibit Hall with Poster Viewing
1:45 Chairperson’s Remarks
Anil Kumar, PhD, Principal Process Engineer, Global MSAT, Sanofi Genzyme
1:50 Production Bioreactor Scale-Down Model Verification Case Study
Michael Mollet, PhD, Principal Scientist, AstraZeneca
2:20 Seed Train Intensification and Dynamic Feeding: Two Ways to Reduce Timelines in Upstream Bioprocessing
Johannes Wirth, MSc, Scientist, Bio Process Science, Rentschler Biopharma SE
The application of intensified and dynamic strategies has widely been used for the improvement of bioprocess performance. In line with this we present case studies where the application of an intensified seed train and dynamic feeding strategies led to
reduced timelines as well as higher product yields. The implementation of these approaches in combination with process automation strategies holds the opportunity to reduce the laboratory effort and enhance production process robustness.
2:50 Development and Adoption of a Single-Use Platform Strategy for Storage and Handling of Frozen Biologics
Anil Kumar, PhD, Principal Process Engineer, Global MSAT, Sanofi Genzyme
This presentation will describe a new approach for the development and integration of a closed loop single-use platform strategy for storage and handling of a frozen formulated biologics substance. The talk will highlight a general approach, benefits,
and challenges associated with transitioning to a bag-based solution for storage and handling of frozen biologics.
3:20 NEW: Biopharm Product’s Structure-Function Relationship (SFR), Rationale for Accelerating Analytical Development and Process Characterization
Wasfi AlAzzam, PhD, CSO, TechnoPharmaSphere (TPS)
SFR aims to measure structural attributes impact on product’s activity and safety profiles, this practice stands true for most pharmaceutics. SFR from in vitro and in vivo provides in-depth understanding of product’s QA and determine CQA,
which help accelerate analytical methods development, acceptance criteria, and product’s specs. SFR results are used to accelerate process characterization, process control strategy, and establishing QBD principles for manufacturing process.
SFR is keystone for justifying analytical development acceleration and process characterization & control.
3:50 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Plenary Keynote Session View details
6:00 A Taste of New England Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
Thursday, August 15
6:00 - 6:45 am Namaste@#BPSMT (Seaport Hotel Plaza Lobby)
8:00 Registration Open and Morning Coffee
8:25 Chairperson’s Remarks
Stefan Schmidt, PhD, MBA, COO and Head, Operations, BioAtrium AG
8:30 Bench-Scale Single-Use Bioreactor Design and Optimization
T. Craig Seamans, PhD, Senior Principal Scientist, Biologics Process R&D, Merck & Co., Inc.
Here we report on optimized design 3-L rigid single-use bioreactors, coupled with automated sampling and feed control. Enhancements to bioreactor design include exploration of micro-sparger materials, along with utilization of CFD for establishing
impeller and baffle configurations. The complete system can evaluate metabolic-based feed strategies for bench scale cell culture processes across multiple vessels, and implementation of the custom bioreactors and automated sampling has improved
plant operational efficiency.
9:00 Disposable Systems for Bioreactor Harvest Clarification
Rustin M. Shenkman, PhD, Senior Upstream Development Engineer, Process Development Biologics, Shire US, Inc., a Takeda Company
Intensified bioreactor processes and the adoption of single-use manufacturing infrastructurehas put a strain on the harvest clarification unit operation. Legacy as well as recent technologies can provide several options for the rapid and efficient
removal of cells and cellular debris from harvest streams. Development-scale evaluations were performed to compare promising technologies in yield and scalability and the results will be presented here.
9:30 Quality Versus Yield Trade-Off in Biosimilar Process Development: Lessons Learned
Menzo Havenga, PhD, CEO, Batavia Biosciences
In generating high expressing biosimilar cell lines, we experienced the need to carefully check every step of the USP trajectory. This presentation will show two study cases where yield was compromised as quality is paramount.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 High Resolution Native LC-MS for Product CQA Assessment and Process Monitoring
Jonathan Bones, PhD, Principal Investigator, Characterization and Comparability Laboratory, National Institute for Bioprocessing Research and Training (NIBRT)
Multi-attribute monitoring has attracted considerable attention recently as process scientists request more information to assist them to develop and understand their bioprocesses. A strategy for multi-attribute monitoring using intact protein separations
coupled to native high resolution mass spectrometry will be described that facilitates the determination of multiple product quality attributes such as glycosylation, deamidation, lysine truncation, etc. Different examples will be presented along
with strategies for inclusion of the platform in an online format.
11:15 Bioprocess Monitoring and Protein Quality Assessment Using Polarized Intrinsic Fluorescence Spectroscopy in Multi-Dimensional Modes: A New Measurement Methodology
Alan G. Ryder, PhD, Professor, Nanoscale Biophotonics Laboratory, Chemistry, National University of Ireland-Galway
Fluorescence polarization (or anisotropy) is related to protein structure, size, and aggregation profile. When implemented using multi-dimensional measurements on intrinsic protein emission, one can quickly extract potentially very useful diagnostic
information. Here we show how polarized excitation-emission matrix (pEEM) measurements have been applied to the monitoring of IgG PEGylation reactions and how very similar pTSFS measurements when applied to bioreactor monitoring using a model
system delivered significant improvements in accuracy.
11:45 A Computational Framework for Mechanistic Modeling and Simulation of Upstream Bioprocesses
Will Johnson, PhD, Principal Engineer, Digital Integration & Predictive Technologies (DIPT), Process Development, Amgen, Inc.
The current benchmark for the digital transformation of upstream bioprocesses is computational fluid dynamics applied to bioreactors, which is limited by its consideration only of the fluid domain. Turning predictive bioreactor models into predictive
bioprocess models requires a multiscale approach combining models of the bioreactor, cell physiology, and subcellular compartments. Here we introduce a computational framework for a digital predictive bioprocess model, and an exemplary model used
to explore hypothetical changes to process setpoints with the goal of optimizing performance.
12:15 pm Enjoy Lunch on Your Own
1:15 Refreshment Break in the Exhibit Hall with Last Chance for Poster Viewing (Sponsorship Opportunity Available)
1:55 End of Conference