Cambridge Healthtech Instituteの第19回年次会議

Cell Line Development & Cell Culture Optimization
(細胞株開発と細胞培養の最適化)

上流工程の生産性とバイオ医薬品の品質の向上

2023年8月14 - 15日、EDT(米国東部標準時)

宿主細胞工学の向上、高発現細胞株、細胞培養プロセスの最適化により、過去10年間で上流工程処理が大幅に加速し、現在の抗体産生量は10g/L以上となっています。当面は、新しいプラットフォームや先端技術により、企業にとって高い生産性と品質を追求する機会を提供し続けます。CHIによる「細胞株開発と細胞培養の最適化」会議では、科学者を招待して、細胞株エンジニアリング、培地最適化、ゲノムエンジニアリングに関する最新情報のほか、新規バイオ医薬品やAAVの生産と分析における上流工程の課題を克服するための戦略について紹介します。

8月14日(月)

Registration and Morning Coffee8:00 am

NEW PLATFORMS AND APPROACHES IN CELL LINE DEVELOPMENT
細胞株開発における新たなプラットフォームとアプローチ

9:55 am

Chairperson's Remarks

Jianfa Ou, PhD, Senior Scientist, Bristol Myers Squibb Co.

10:00 am KEYNOTE PRESENTATION:

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.

10:30 am

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.

11:00 am

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.

11:30 am Integrating Synthetic Biology and Computer-Aided Design to Advance Biologics Production in CHO Cells

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.

12:00 pm LUNCHEON PRESENTATION:Luncheon Presentation to be Announced

Speaker to be Announced

Session Break12:30 pm

MEDIA OPTIMIZATION
培地の最適化

12:50 pm

Chairperson's Remarks

Laura Zielewicz, PhD, Senior Scientist, Pfizer Inc.

12:55 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.

1:25 pm

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
DoEとQbDの原理を活用して細胞培養プロセスを最適化

2:40 pm

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.

3:10 pm

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
基調講演:今日の課題を解決する

4:20 pm

Chairperson's Remarks

Susan D'Costa, PhD, CTO, Alcyone Therapeutics, Inc.

4:30 pm

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.

5:00 pm

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

8月15日(火)

Registration and Morning Coffee7:30 am

GENOME ENGINEERING
ゲノムエンジニアリング

7:55 am

Chairperson's Remarks

Ping Liu, PhD, Associate Director & Head of Cell Line Development, REGENXBIO, Inc.

8:00 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.

8:30 am

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.

9:00 am

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.

9:30 am Strategies for Cell Line and Process Development that Support Current and Next-Generation Products and Processes

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

10:45 amBreakout Discussion Groups

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.

11:30 am

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.

12:00 pm

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
新規モダリティに対する上流工程の生産の課題

2:10 pm

Chairperson's Remarks

Saurabh Sen, PhD, Associate Director, Cell Line Development, Genomic Medicine Unit CMC, Sanofi

2:15 pm

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.

2:45 pm

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.

3:15 pm

A New HeLaS3 Subclonal Cell Line for AAV Gene Therapy

Saurabh Sen, PhD, Associate Director, Cell Line Development, Genomic Medicine Unit CMC, Sanofi

Refreshment Break in the Exhibit Hall with Poster Viewing3:45 pm

4:30 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.

5:00 pm

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


* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

参加型パスのお申込みは終了致しました。
オンデマンドパスは引き続きお申込み頂けます。
下記ボタンよりご連絡下さい。

Choose your language
English


BIOMANUFACTURING AND DIGITIZATION