Cambridge Healthtech Instituteの第19回年次会議
Cell Line Development & Cell Culture Optimization
2023年8月14 - 15日、EDT（米国東部標準時）
Registration and Morning Coffee8:00 am
NEW PLATFORMS AND APPROACHES IN CELL LINE DEVELOPMENT
Automation in Cell Line Development
Lina Chakrabarti, PhD, Assoc Principal Scientist, AstraZeneca
Automating cell line development (CLD) and cell culture workflow enables (1) early enrichment of high producer and high-quality clones, (2) increased process consistency and screening throughput, (3) enhanced resource efficiency, (4) generation of reliable and reproducible results, and (5) improved data traceability and integrity. Hence, establishment of an automated platform in CLD offers multi-faceted advantages for developing desirable cell lines to be used for biomanufacturing.
Pfizer's Targeted Integration Platform Enables Development of Robust and Stable Cell Lines on Accelerated Timelines
Laura Zielewicz, PhD, Senior Scientist, Pfizer Inc.
Speed to regtox and clinical trials has become a common paradigm in the pharmaceutical industry. Pfizer’s targeted integration CHO host provides the platform for developing robust cell lines on accelerated timelines. The platform utilizes an engineered dual-landing pad and multiple-copy vectors to develop cell lines with predictable and stable genotype, growth characteristics, and production of standard mAbs, multi-specifics, and fusion proteins, which is critical to enable acceleration.
Sequence Variants Determination via NGS for Cell Line Screening
Grace Yi-Wei Huang, PhD, Scientist, IGM Biosciences, Inc.
Proteomic methods and Sanger sequencing have been used in cell line development for over a decade, but the advent of next-generation sequencing (NGS) has revolutionized the screening and characterization of cell lines for biologics production. IGM Biosciences uses NGS to identify sequence variations and evaluate cell line genotypes relating to their growth and productivity. We will discuss the benefits of utilizing these sequencing technologies when selecting lead clones.
Scott Estes, PhD, Head of Cell Line Development, Asimov
In this talk, we present a CHO platform that moves beyond the one-size-fits-all paradigm by tailoring vectors for each molecule to optimize expression. Our system combines a GS knockout CHO host, transposase, genetic libraries, and computational tools. These tools enable development of high-expression lines, fine-tuning of chain expression, and ML-based optimization. We present case studies highlighting the impact of these tools to optimize expression for both standard monoclonal and bispecific antibodies.
Session Break12:30 pm
Media Optimization for Robust CHO Cell Culture Process
Jianfa Ou, PhD, Senior Scientist, Bristol Myers Squibb Co.
Process intensification, including implementation of highly concentrated media, is widely pursued to improve process yield and reduce footprint for monoclonal antibody production. Media preparation parameters contribute significantly to media quality, cell culture performance, and productivity. Thus, it is important to understand and develop proper media preparation procedure for robust CHO cell culture process. Here we evaluated the key parameters on media stability by cell culture and different process analytical technologies.
Leveraging AstraZeneca's Proprietary Media and Feeds to Improve Yield for a Commercial CHO-Derived Therapeutic Protein
Jessica Kenney, Senior Process Engineer, Biologics Drug Substance Tech Transfer, Alexion, AstraZeneca Rare Disease
This talk will give an overview of the development of a next-generation upstream manufacturing process for a CHO-derived therapeutic protein to significantly improve yield, reduce cost of goods, and ultimately serve more patients with rare diseases. Newly accessible AstraZeneca proprietary media and feeds were leveraged to achieve this goal, with modifications to the platform feeding strategy leading to an increase in titer of ~33%.
Sponsored Presentation (Opportunity Available)1:55 pm
Networking Refreshment Break2:25 pm
LEVERAGING DOE AND QBD PRINCIPLES TO OPTIMIZE CELL CULTURE PROCESSES
Achieving High Titer in a Non-Platform CHO Process when Converting to an Internal Medium Platform
Thomas Hayes, BSE, Senior Scientist, Cell Culture Development, Sanofi
A non-platform CHO process using proprietary commercial medium was internalized, and initial results in our internal platform process showed a 3-fold decrease in productivity. Using quality-by-design principles, we identified key medium components and process parameters that significantly increased cell-specific productivity, and after optimization a 5-fold increase in titer was achieved in an internal medium platform. The final optimized process was scaled from AMBR250 and benchtop bioreactors to pilot-scale single-use bioreactors to demonstrate process and scale-up robustness.
Leveraging DoE Modeling to Optimize Cell Culture Performance Attributes of a Null Cell Pool for Developing a Process-Specific HCP Reagent
Wilhad H. Reuter, Lead Engineer, Upstream Process Development, Alkermes, Inc.
This case-study will address the methodologies for cell culture optimization to generate a process-specific HCP reagent, recommended for late-stage product characterization. A combination of screening DoE and OFAT experimentation was implemented to identify optimal process conditions in the ambr15 miniature bioreactor system. These conditions were then implemented in a 2 L single-use bioreactor system to show comparable growth attributes and HCP production to that of the original producer cell line.
Session Break and Transition to Plenary Keynote Session3:40 pm
PLENARY KEYNOTE: SOLVING TODAY'S CHALLENGES
Overcoming the Challenges of Bioprocesses: The Future of Biomanufacturing
Glen R Bolton, PhD, Executive Director, Late Stage Bioprocess Development, Amgen Inc
Novel therapies and technologies are emerging to meet the needs of patients; however, the manufacturing of biopharmaceuticals remains a complex and challenging process. As demand for biopharmaceuticals grows, the industry faces new challenges in terms of scalability, cost, and process robustness. The implementation of innovative technologies to improve process efficiency and the importance of process control and data analytics in ensuring process robustness are key levers to meet these challenges.
Commercializing Gene Therapies - The Combined Power of Patient Advocacy and Cost-Effective Manufacturing
Rachel Salzman, DVM, Founder, The Stop ALD Foundation & Global Head, Corporate Strategy, Armatus Bio
There is only a very small handful of FDA-approved gene therapies. This presentation will examine the development of an FDA-approved gene therapy where patient advocacy played a critical role resulting in the first-ever clinical use of a lentiviral vector. Although manufacturing continues to represent a significant challenge throughout the entire R&D journey, there are opportunities for advocacy and manufacturing communities to seek alignment and combine their collective powers to achieve the common goal of increasing patient access to transformative medicines.
Welcome Reception in the Exhibit Hall with Poster Viewing5:30 pm
Close of Day6:30 pm
Registration and Morning Coffee7:30 am
Genome Engineering and Cell Line Development to Facilitate Drug Development
Metewo S. Enuameh, PhD, Senior Scientist, Vector Core Cell Line Development, REGENXBIO, Inc.
Developing cellular models of disease have the potential to facilitate and/or accelerate the drug discovery and development. At REGENXBIO, we are evaluating the use of genome engineering and cell line development approaches, to generate mammalian disease cell line models that have utility in the screening of drug candidates. These models should facilitate the robust advancement of gene therapy products from the lab bench to the clinic.
MAD7 Nuclease Activity in CHO Cells
Geneva Alok, PhD, Process Development Scientist, Amgen
Manufacturing cell lines can benefit from host cell engineering to improve performance and product quality. MAD7 is an engineered class 2 type V-A CRISPR-Cas nuclease (Cas12a/Cpf1) shown to function in a variety of systems, recently including CHO cells. MAD7 can successfully facilitate site-specific indels and knock-ins in CHO, making it a useful tool for engineering in cell line development.
Population Dynamics, Phenotypic Heterogeneity, and Age: Shifting Expression Patterns in Stable and Unstable Clonally-Derived CHO Populations
Theodore Peters, PhD, Senior Scientist, Cell Line Development, Seagen
CHO cell lines have significant phenotypic variability though derived from a single cell progenitor. This variability may lead to or be indicative of the propensity of a cell line to exhibit production instability over time. Here we characterize RNA expression from stable and unstable cell lines using single-cell RNA sequencing. Our work shows that clonally derived cell lines are complex metapopulations with distinct subpopulations that change differently with time. We explore how this changing metapopulation may influence production stability and search for stability signals in those subpopulations that drive changes within the metapopulation.
Leon Pybus, Associate Director, Process Strategy & Development, FUJIFILM Diosynth Biotechnologies
mAbs produced in fed-batch mode by CHO cell lines have a low risk profile and platform approaches to development, manufacturing technology, and infrastructure allow for rapid IND submission. Next-generation products (e.g., bispecifics) and processes (e.g., perfusion) can stretch this mAb platform paradigm and necessitate increased development. This requires a revaluation of mAb platform components to enable rapid development of current and next generation products and processes.
Coffee Break in the Exhibit Hall with Poster Viewing10:00 am
Breakout discussions provide an opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Please visit the breakout discussions page on the conference website for a complete listing of topics and descriptions.
Synthetic Genetic Parts and Engineering Systems for Biologics Production
Yusuf B. Johari, PhD, Principal Bioengineer, SynGenSys
Synthetic biology based on the “Design-Build-Test-Learn” cycle offers a new paradigm for genetic vector design, where it is possible to engineer a host cell factory in a product or cell type specific manner via combinatorial tuning of discrete cellular synthetic processes. This approach permits “one-size fits-all” genetic parts and vectorology to be replaced with tailored design and construction of specifically fit-for purpose genetic systems. Utilizing a platform of genome-scale mining and informatic tools, we generate libraries of engineered/synthetic parts with user-defined functionality that can boost biologic manufacturability and specificity via context-specific control of primary cellular processes.
Impact of Sf-rhabdoviral Contaminants of Insect Cell Lines on Biosafety Profile of the Baculovirus-Insect Cell System
Donald L. Jarvis, PhD, Professor, Molecular Biology, University of Wyoming
The insect cell lines widely used as hosts in the baculovirus-insect cell system are contaminated with adventitous viruses. We assessed the infectivity of Sf-rhabdoviruses for mammalian cell lines and immunocompromised mice to determine their impact on the biosafety profile of this biologics manufacturing platform.
Sponsored Presentation (Opportunity Available)12:30 pm
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own1:00 pm
Refreshment Break in the Exhibit Hall with Poster Viewing1:30 pm
UPSTREAM PRODUCTION CHALLENGES FOR NOVEL MODALITIES
Addressing the Challenges for Production and Analysis of AAV Vectors
Helen Young, PhD, Manager, Synthetic & Mammalian Upstream, CPI
Developing high-yielding, scalable and commercially viable processes for AAV manufacture, with associated analytical methods for assessing the CQAs, presents challenges. Here we present work being performed at CPI to address some of the upstream challenges, including development of an intensified N-1 seed train step to reduce inoculum requirements. Further, we discuss some of the approaches we have been working on for full and empty capsid determination, including mass photometry.
Advancing AAV Transient Expression Platform by Cell Line Engineering, Host Cell Engineering, and Plasmid Optimization
Ping Liu, PhD, Associate Director & Head of Cell Line Development, REGENXBIO, Inc.
To improve AAV transient titers in HEK293 system, REGENXBIO had made significant efforts in host cell line development and engineering. In addition, we generated new plasmid expression systems by several rounds of plasmid optimization. Combining the new cell lines and plasmids, we increased our overall transient yield significantly while improving the product quality.
Refreshment Break in the Exhibit Hall with Poster Viewing3:45 pm
It All Starts with One Vial: Cell Banking to Enable GMP Manufacturing
Charu Garg, PhD, Senior Scientist, Process Cell Sciences, Merck
Using a CDMO for GMP cell banking is mainstream in the biopharmaceutical industry. There are potential challenges to successfully manage the tech transfer process. Key factors to generate a successful GMP cell bank include 1) sourcing appropriate raw materials, 2) identifying the correct equipment and its setting, and 3) defining growth parameters, freezing condition. Application of a systematic approach can help ensure the successful generation of a GMP cell bank.
Fed-Batch Fermentation AMBR250 Model Establishment and Its Utilization in Vaccine Development
Zhiguo Liu, PhD, Senior Scientist, Merck
Advantageous in its high throughput and process automation degree, the AMBR250 platform is gaining industrial adaptation. Here we report a successful ‘fit-for-purpose’ AMBR250 scale-down model case-study for a vaccine bioprocess. This gas-transfer-guided model development not only demonstrates representative process attributes, but also produced statistically equivalent productivity of target product, enabling a faster process evaluation platform to match an accelerated project timeline.
Close of Cell Line Development & Cell Culture Optimization Conference5:30 pm