Cambridge Healthtech Instituteの第8回年次会議

Gene Therapy CMC and Analytics


2023年8月14 - 15日、EDT(米国東部標準時)

Cambridge Healthtech Instituteの「遺伝子治療薬のCMCとアナリティクス」会議では、臨床・商業供給用のウイルスベクターベースの遺伝子治療薬の分析・特性評価・品質が直面する現実的な課題を明らかにします。CMC戦略、原材料、ポテンシーアッセイの開発、アナリティクス手法、カプシドの定量化、安定性、ベクターの安全性と品質の向上に対する機械学習の影響に関する専用セッションがあります。


Registration and Morning Coffee8:00 am


9:55 am

Chairperson's Remarks

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


Commercializing Gene Therapies

Vesselin Mitaksov, PhD, Associate Research Fellow, Global Biologics, Pfizer Inc.

The presentation will focus on Pfizer's experience with late-stage rAAV product development in preparation for commercialization. Case studies presented will highlight aspects of rAAV control strategy development and eventual implementation for commercial manufacture. Examples will include challenges and solutions associated with product and process understanding to identify and control product critical quality attributes and to inform a comprehensive comparability assessment to support process changes throughout rAAV product development history.


Preparing for Launch and Late-Stage Development


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

  • Feedback from approved / late-stage therapies 
  • CMC concerns
  • Cost analysis 
  • Potency assay strategies

Lyndi Rice, PhD, Head, Gene Therapy Analytical Technologies, BioMarin

Mark Galbraith, PhD, Vice President, Analytical Sciences, Affinia Therapeutics

Svetlana Bergelson, PhD, Senior Director, Technology Development, Biogen

Vesselin Mitaksov, PhD, Associate Research Fellow, Global Biologics, Pfizer Inc.

Santoshkumar L. Khatwani, PhD, Director, Analytical Development, Sangamo Therapeutics

11:30 am Talk Title to be Announced

Speaker to be Announced

Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:00 pm

Session Break12:30 pm


12:50 pm

Chairperson's Remarks

Mark Galbraith, PhD, Vice President, Analytical Sciences, Affinia Therapeutics

12:55 pm

Gene Therapy Potency Methods: Method Lifecycle Management and Optimization

Lyndi Rice, PhD, Head, Gene Therapy Analytical Technologies, BioMarin

Potency methods remain a significant challenge for gene therapy programs and can lead to program delays. Best practices for potency method development, transfers, and validation will be discussed, including proven analytical strategies of lifecycle management for potency methods. Case studies demonstrating method comparability considerations and method optimization for validated methods will also be covered.

1:25 pm

Bioassay Strategy for Early Clinical Phases

Ping Carlson, PhD, Director, Bioassay, Passage Bio

Potency is the Critical Quality Attribute (CQA) for Gene Therapy (GTx) manufacturing most related to the MoA of GTx. This presentation will discuss strategies for potency method development, phase-appropriate validation, method bridging, and life cycle management.

Sponsored Presentation (Opportunity Available)1:55 pm

Networking Refreshment Break2:25 pm

2:40 pm

Development and Optimization of a Functional Potency Assay for Late-Stage AAV Gene Therapy

Debashree Basu, PhD, Senior Scientist, Analytical Development, Ultragenyx Pharmaceuticals

Potency is a critical quality attribute and potency assays are an important regulatory requirement of late-stage AAV gene therapy. A functional potency assay quantitatively measures a Mechanism-of-Action (MOA)-based biological function. In this presentation, development and optimization of a quantitative, MOA-based in vitro functional potency assay for an AAV gene therapy product will be discussed. Challenges in cell line development and strategies for their resolution will be explored as well.

3:00 pm

Potency Assay Development Strategies for Gene Therapy Targeting Muscular Dystrophy

Rajeev Boregowda, PhD, Director, Analytical Development, Solid Bio

The delivery of a functional gene or transgene to a target cell requires a thorough understanding of its complex mechanism of action (MOA). Among analytical methods facilitating such understanding is the cell-based in vitro bioassay and it is one the critical release and stability indicating methods.  Due to complexities around the MOA of gene therapies, more than one in vitro method is required to truly represent the MOA. To implement the in vitro methods in a GMP environment, they should be objective in their measurements and be easily executable in QC laboratories.

3:20 pm

NGS Technology Application in Genomic Medicine Unit of Sanofi

Wei Zhang, PhD, Senior Scientist, Sanofi

The goal of the NGS group in Sanofi GMU (Framingham MA) is to establish NGS based assays to complement and/or replace the complicated mix of in vitro/in vivo assays, leading to accelerated development and expedited release testing. A multi-attribute NGS assay for DNA identity and residual DNA contamination was developed using a PCR free library prep method. This method improved overall genome coverage depth, the accuracy of relative quantification of residual DNA, and variant calling confidence. This presentation will discuss the development of the method, provide case studies of use, as well as provide a high level method validation strategy.

Session Break and Transition to Plenary Keynote Session3:40 pm


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


Registration and Morning Coffee7:30 am


7:55 am

Chairperson's Opening Remarks

Xiaohui Lu, PhD, Director, Analytical Development, Ultragenyx Pharmaceutical

8:00 am

Development of USP Standards to Support Gene Therapy Products

Anthony Blaszczyk, PhD, Senior Scientist, Global Biologics, US Pharmacopeia

Establishing relevant and applicable standards that apply to gene therapy is essential to maintaining safe and effective therapeutics, but the complexity and diversity of gene therapy products present unique challenges. USP is working with stakeholders and scientific experts to address the challenges of standardizing materials and methods. This presentation will focus on the development of documentary and physical standards to support analysis of gene therapy products, process residuals, and raw materials.

8:30 am

Impurity Analysis of Gene Therapy Products

Santoshkumar L. Khatwani, PhD, Director, Analytical Development, Sangamo Therapeutics

This presentation will focus on the importance of demonstrating impurities clearance from the gene therapy products. In addition, some of the analytics necessary to evaluate impurities will be discussed. Topics include: importance of evaluating impurities in gene therapy products; type of impurities; analytics for measuring impurities; and demonstrating process performance for impurity clearance.

9:00 am

Analytical Toolbox for Characterizing Empty, Partial, and Full AAV Capsids and Linking Genome to Function

Aisleen McColl-Carboni, PhD, Senior Director, Analytical Development, Oxford Biomedica Solutions, Inc.

Manufacturing of AAV vectors is known to produce three types of capsids: empty, partial, and full. To specifically determine the impact of partial and empty capsid impurities on potency, an AAV preparation with a high amount of empty and partial capsids was separated into full, partial, and empty capsid populations and subjected to full analytical characterization. Capsid, genome, and potency data will be presented.

9:30 am Talk Title to be Announced

Speaker to be Announced

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.


Formulation, Stability, Delivery, and Forced Degradation Studies

Kruti Soni, PhD, Scientist, Technical Development, Biogen


11:30 am

Analytical Development Toolbox for Characterization of Empty, Full, and Partial Capsids

Shreya Ahuja, PhD, Senior Principal Scientist, Analytical Department, Prevail Therapeutics

The development of AAV drugs involves assessing critical quality attributes using analytical methodologies. Assessment and quantification of empty/full ratios have proven to be challenging across the industry. Analytical ultracentrifugation is a gold-standard technique that has been used for years but it has its limitations. We have explored SEC-MALS, Mass Photometry, IEX, Capsid/vg ratio, and A260/280 to mitigate the drawbacks of analytical ultracentrifugation and have expanded our AAV characterization panel.

12:00 pm

Analytics - Characterization of AAV Drug Product

Xiaozhu Sue Duan, Associate Director, Analytical Development, Astellas Gene Therapies

Stressed AAV drug product was analyzed in several stability indicating assays. Results indicated that in vitro assay was much more sensitive accessing degradation than in vivo assay. Among the stress conditions, a series of studies of photodegradation of white fluorescent light (WFL) were performed. The loss of potency was associated with total WFL exposure and was independent of the intensity.

12:30 pm Talk Title to be Announced

Speaker to be Announced

1:00 pm LUNCHEON PRESENTATION:Luncheon Presentation to be Announced

Speaker to be Announced

Refreshment Break in the Exhibit Hall with Poster Viewing1:30 pm


2:10 pm

Chairperson's Remarks

Santoshkumar L. Khatwani, PhD, Director, Analytical Development, Sangamo Therapeutics

2:15 pm

Characterization of Critical Raw Material Impact on rAAV Product Quality within the Context of a Transfection-Based HEK Production Process

Jessie Sun, PhD, Director, Ultragenyx Pharmaceutical, Inc.

Transient transfection using HEK293 cells is one of the most common platforms for producing recombinant adeno-associated virus (rAAV). During the process development supporting multiple Phase III products, upstream parameters and raw material were fully characterized using quality-by-design approach. Critical raw materials including polyethylenimine and plasmids were identified due to potential impact on productivity and product quality. Comprehensive characterization including multiple DOEs has resulted in establishing control on these critical RMs to ensure consistent manufacture of high-quality product.

2:45 pm

Comparability Strategies for Gene Therapies

Lauren M. Drouin, PhD, Director, Analytical Development, Genomic Medicine, Alexion, AstraZeneca Rare Disease

The manufacturing process for LB-001, an AAV gene editing vector designed to treat methylmalonic academia, was optimized to streamline the purification process and increase final product yield. An analytical comparability assessment was performed to evaluate the AAV gene editing material pre- and post-manufacturing process changes. Here we show that the process changes improved product quality and provide supporting analytical data.


3:15 pm

Formulation Activities from an Analytical Perspective

Jonathan Hill, Senior Scientist, Analytical Development, Solid Biosciences, Inc.

The scope of formulation activities can range from a simple screen to confirm the performance of an optimized matrix to a full-scale development of a new buffer system from scratch. A constant across the spectrum of formulation activities is the need for analytical tools to evaluate the effectiveness of the test matrices to confer stability while avoiding deleterious effects. This presentation will highlight the analytical techniques available while exploring the effects of forced degradation and storage stability conditions.

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


4:30 pm

Mass Spectrometry for Post-Translational Modifications (PTM) Analysis

Yiling Bi, PhD, Senior Scientist, Sangamo Therapeutics

Post-translational modifications (PTMs) of biologics can occur during the production and storage stages. Due to the chemical modification changes, the potential impact on drug safety, quality, and efficacy needs to be closely monitored. In this presentation, we will focus on PTM analysis of AAV-based gene therapy drug products and in-process samples using mass spectrometry (MS) approach, and discuss the functional implications as well.

5:00 pm

Analysing Structure/Function in Gene Therapy

McKay Wood, PhD, Senior Scientist, Analytical Development, Sanofi

Close of Gene Therapy CMC and Analytics 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。


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