Cambridge Healthtech Institute’s 7th Annual
Bioproduction: Scale, Bioreactors & Disposables
Making It Work
Part of CHI's Ninth Annual The Bioprocessing Summit
August 23-24, 2017 | Westin Copley Place | Boston, MA
The 7th annual Bioproduction conference examines biologics production, including scale-down models, scaling up production, engineering bioreactors, single-use systems, and ensuring quality, within the context of increasing productivity. A holistic review
of bioprocessing will be explored, as well as practical details, such as monitoring and analyzing processes, and looking in-depth into how bioreactors process cells. The conference will address robust manufacturing processes and next-generation technologies,
while improving manufacturing platforms and ensuring product quality.
Final Agenda
Wednesday, August 23
7:00 am Registration Open and Morning Coffee
8:05 Chairperson’s Opening Remarks
Stefan Schmidt, Ph.D., M.B.A., Senior Vice President, Process Science and Production, Rentschler Biotechnology
8:15 OPENING KEYNOTE PRESENTATION:
Driving Continuous Improvements for Biologics Manufacturing
Kenneth D. Green, Ph.D., Head, Technical Services, Recombinant Protein Therapies, Shire Human Genetic Therapies
This presentation will discuss opportunities for continuous improvement utilizing operational excellence and innovative approaches to deliver process robustness, manufacturing reliability, and productivity gains.
9:00 FEATURED PRESENTATION:
Challenges with Biologics Process Development and Tech Transfer for Non-Antibody Non-Platform Molecules
Kumar Dhanasekharan, Ph.D., Senior Director and Head, Biologics Process and Analytical
Development, Amicus Therapeutics
This talk will address general challenges with process development for complex glycoproteins, including the use of cell culture perfusion and associated challenges, downstream challenges with HCP reduction, and also overall scalability and manufacturability
of this important class of biologics. Dr. Dhanasekharan will offer insights with examples on tackling some of the challenges encountered.
9:30 Cell Culture Scale Translation from a 24-Well Single-Use Miniature Bioreactor -- New, Unpublished Data
Frank Baganz, Ph.D., Senior Lecturer, Biochemical Engineering, University College London (UCL)
The need to bring new biopharmaceutical products to market more quickly and to reduce final manufacturing costs is driving early-stage, small-scale bioprocess development. This presentation will cover the engineering characterisation of a single-use 24-well
parallel miniature bioreactor (MBR) in terms of power input, liquid phase mixing and oxygen mass transfer. Examples will be given for the application of this MBR to rationally scale cell culture processes.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Designing a 3-L Rigid SUB System: Characterization, Autosampling, Nutrient Control -- New, Unpublished Data
T. Craig Seamans, Ph.D., Senior Principal Scientist, Bioprocess Technical Operations, MRL BioProcess
Development, Merck & Co., Inc.
The presence of resource-efficient systems for examining complex process options is key to effective upstream development. Here we report on enhanced design 3-L rigid single-use bioreactors (SUBs), coupled with completely automated sampling and feed control.
The system can evaluate metabolic-based feed strategies for bench scale cell culture processes across multiple vessels. Implementation of the custom SUBs and automated sampling, has enabled enhanced process development capability, by introducing technology
to both improve operational efficiency and provide a pragmatic new tool to study optimization and robustness.
11:15 Improved Antibody Quality and Consistency in CHO Cells Using a Novel Media Supplement
Adam Elhofy, Ph.D., CSO, Bio-Ess Laboratories, LLC
There has been a push to improve consistency and quality of glycolytic patterns. Protein synthesis and post-translational modification occurs on the lipid membranes of the ER and Golgi. Addition of Cell-Ess improves the consistency and quality of glycosylation
while also increasing titer. The use of Cell-Ess resulted in significantly less variation of the glycolytic pattern and increased higher order glycoforms. The novel method of adding lipids results in an improvement of protein quality and consistency.
11:45 Cell Culture Scale-Up in BioBLU® c Rigid-Walled, Single-Use Bioreactors from Eppendorf
Stacey Willard, Ph.D., Senior Technical Applications Specialist – Bioprocess, Eppendorf
Bioreactor scalability is critical for process development. We analyzed BioBLU Single-Use Vessels (maximum working volumes of 0.25L, 3.75L, 40L) and determined a scalable tip speed zone, kLa values, and using computational fluid dynamics simulations,
power numbers. These data were used to scale-up a process for antibody production in CHO cells.
12:00 pm Sponsorship Presentation (Opportunity Available)
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12:15
Luncheon Presentation: Intensified Bioprocessing is Almost Here: An Update on Modular, End-to-End Continuous Automation
Barbara Paldus, Ph.D., Vice President and General Manager, Finesse,a part of Thermo Fisher
Scientific
Continuous processing has been used successfully for many years in manufacturing industries such as food, chemicals, and steel. When applied to biomanufacturing and combined with single-use technology (SUT), continuous processing offers higher
throughput and increased flexibility. SUT also enables the move from single-product processes to multi-product facilities. As transformative as SUT has been, the bigger shift will be combining single-use workstreams with continuous automation
in a new modular architecture that reaches from inoculation through ultra-filtration.
1:00 Session Break
1:45 Chairperson’s Remarks
Frank Baganz, Ph.D., Senior Lecturer, Biochemical Engineering, University College London (UCL)
1:50 Case Studies: Scale-Down Model Development and Optimization for Screening Raw Materials -- Case Study
Angela Au, Ph.D., Engineer II, Research & Development, Bristol-Myers Squibb Co.
Understanding the relationship between key operating parameters and culture performance is dependent on having a robust scale-down model (SDM) which is an appropriate representation of the drug substance quality attributes and the proposed manufacturing
scale. Raw material variability between suppliers and between lots can impact process performance. Case studies will demonstrate challenges with development and optimization of a SDM sensitive enough to screen raw materials for their impact
at scale.
2:20 Interactive Panel Discussion
Moderator: Richard Altman, M.S., Scientist V, Protein Technologies, Amgen
Panelists:
Angela Au, Ph.D., Engineer II, Research & Development, Bristol-Myers Squibb Co.
Kumar Dhanasekharan, Ph.D., Senior Director and Head, Biologics Process and Analytical Development, Amicus Therapeutics
Jochen B. Sieck, Ph.D., Head, Perfusion Systems Laboratory, Perfusion Systems and Cell Culture Media R&D, Merck Life Science
- Scale-down model uses
- Solving scale-up issues
- Resolving problems using scale-down models
- How scale-down models are being employed in industry
2:50 Scale-Down Model Development for a 5000-L Production Bioreactor Process Using 5-L Bioreactor Systems: A Case Study
Jeremy Discenza, M.Sc., Associate Scientist II, Bristol-Myers Squibb Co.
A 5-L lab-scale bioreactor scale-down model (SDM) was developed to simulate monoclonal antibody production in a 5000-L bioreactor. The results of 5-L bioreactor runs demonstrated acceptable product quality but higher titer compared to the
5000-L production bioreactor. Process performance analysis culminated in a change in aeration strategy, resulting in a yield improvement at the commercial scale.
3:20 Bioreactor Scale-Down Model Alterations to Better Predict Product Quality of Large Scale
Laurie Hazeltine, Ph.D., Research Scientist, Cell Culture – Late Phase, Eli
Lilly and Company
A scale-down model that accurately predicts cell growth, titer, and product quality is important for effective biopharmaceutical development. For one molecule in development at Lilly, difference in a critical quality attribute (CQA) was observed
between small and large-scale bioreactors. While keeping scale independent parameters constant, other process parameters were investigated. Dissolved carbon dioxide was identified as one contributing factor to the CQA difference between
scales. An improved scale-down model was developed to support the manufacturing control strategy.
3:50 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 PLENARY KEYNOTE PRESENTATION
6:00 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 Close of Day
Thursday, August 24
8:00 am Registration Open and Morning Coffee
8:25 Chairperson’s Remarks
Jeremy Discenza, M.Sc., Associate Scientist II, Bristol-Myers Squibb Co.
8:30 Flexible and On-Demand Production of Therapeutic Biologics Using a Portable Device -- New, Unpublished Data
Jicong Cao, Ph.D., Postdoctoral Associate, Biological Engineering, Massachusetts Institute of
Technology (MIT)
By combining genetic and hardware engineering, we developed a portable platform to produce multiple proteins on demand in an integrated microfluidic device. We created genetically engineered Pichia pastoris strains, which can produce one or more proteins of interest on programmable cues, and demonstrated the near-single-dose production of these biologics within 24 hours. The system allows people living in remote areas to get rapid access
to therapeutic biologics at the point-of-care.
9:00 Performance and Product Quality Implications of Bioreactor Perfusion via Single-Use Centrifugation vs. Tangential Flow Filtration -- Case Study
Rustin M. Shenkman, Ph.D., Senior Development Engineer, BDS Process Development,
Shire
A perfusion bioprocess for a therapeutic protein was developed for tangential flow filtration (TFF) and single-use centrifugation technologies. TFF has a wider industry base and familiar scaling paradigm whereas as single-use centrifugation
has a limited industry base but, unlike microfiltration, does not suffer from product retention. Cell culture performance and drug substance (DS) quality attributes were similar scales and retention technologies. However, DS produced
via TFF had decreased room-temperature stability.
9:30 Sponsored by: The Windshire Group, LLC
Continued Process Verification and Process Monitoring Using ProcessPad
James Blackwell, Ph.D., MBA, President, The Windshire Group, LLC
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Achieving Seamless Scale-Up and Technology Transfer – A Case Study in Single-Use Bioreactors -- Case Study & New, Unpublished Data
Ying Wang, Ph.D., Senior Scientist I, Manufacturing Sciences, AbbVie Bioresearch Center
A systematic scale-up strategy is critical in enabling a rapid and robust technical transfer. For a program involving a CHO cell culture process, a combination of mass-transfer (kLa) studies, computational simulation and scale-down
model experiments were used within this newly developed work-flow. Utilizing this approach, scale-up was successfully accelerated (<4 months) with titer improvement and comparable product quality. The main lessons learned
from this case study will be presented.
11:15 Scale-Up of a High Cell Density Perfusion Culture Using Only Single-Use Systems -- New, Unpublished Data
Richard Rohe, M.Sc., Scientist, API Large Molecule, Johnson & Johnson
A case study will be presented on scale-up of a perfusion process from 10L bench-top bioreactor to 1000L SUB system connected to an external single-use cell retention system for production of a virus based product. Cells were
grown in the seed bioreactor, 250L SUB system, to high cell density using a perfusion process to inoculate and infect cells with a virus stock at high cell density in the 1000L production bioreactor. To scale up the process,
the seed and production SUB systems configuration were changed to connect single-use cell retention system, to implement an aeration strategy to meet OTR and to strip CO2 from the culture and to provide sufficient power
per unit volume.
11:45 Disposables in Bioprocessing: Catalogue or Customization – Options and Limits of Flexibility
Stefan Schmidt, Ph.D., M.B.A., Senior Vice President, Process Science
and Production, Rentschler Biotechnology
On the one hand, the recent success of disposables in bioprocessing is directly related to being off the shelf catalogue products which are mass produced at competitive prices. On the other hand, single-use equipment offers
huge benefits through the ability of being customized and on-purpose designed. Due to many years of intense use of disposable material, we will give advice on the customization, the related flexibility benefits and strategies
to successfully navigate between catalogue and customized products.
12:15 pm Enjoy Lunch on Your Own
1:15 Dessert Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing
1:55 Close of Conference