Cambridge Healthtech Institute’s 3rd Annual

Gene Therapy CMC and Analytics

Regulation and Analysis of Vector-Based Gene Therapies

August 14-15, 2019


Gene therapy is an extremely promising technique for the treatment of incurable diseases such as cancer and genetic disorders such as hemophilia. However, the analysis, characterization and delivery of these unique products remain a key issue.

Cambridge Healthtech Institute’s Gene Therapy CMC and Analytics meeting uncovers the practical challenges facing vector-based gene therapy analytics, assay development, quality control, vector development and delivery.

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


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8:05 Chairperson’s Remarks

Michael Kelly, PhD, VP, Process Development, AVROBIO

8:15 KEYNOTE PRESENTATION: Regulation and Challenges in Developing Vector-Based Gene Therapies

Heidaran_MoMo Heidaran, PhD, Vice President, Technical, PAREXEL Consulting, PAREXEL International

While it is assumed that regulatory approval often leads to commercial success, this may not become an overwhelming trend in the field of gene therapy. The major reasons for this disconnect will be discussed in my presentation but full understanding of how these products work (knowledge of the product) and how these products could be consistently manufactured must be an essential part of the product development cycle.

9:00 USP Standards Development Activities to Support Gene Therapies

Jim Richardson, PhD, Senior Science and Standards Liaison, Global Biologics, United States Pharmacopeia

Gene therapy offers tremendous promise to address human disease but their complexity and diversity present unique challenges. USP is engaging with stakeholders to identify and develop documentary and physical standards to support gene therapy. This presentation will provide an overview of general chapters <1043> Ancillary Materials for Cell, Gene, and Tissue-Engineered Products, and <1047> Gene Therapy Products as well as an update on documentary and physical reference standards under development.

9:30 Developing CMC Strategies to Advance a Gene Therapy Pipeline

Gangurde_RajivRajiv Gangurde, PhD, Director, CMC Portfolio Management, Voyager Therapeutics

This presentation discusses Voyager’s overall development strategy for AAV-gene therapy, to support a diverse gene therapy portfolio. The development paradigm primarily involves a two-stage approach: one encompassing development activities leading to drug product manufacture for Phase 1/IND filing studies, and the other directed to late-stage/commercial manufacture for approval/launch-enabling pivotal studies. Ways to balance early CMC investment and optimize resources, focusing on opportunities to expedite and de-risk CMC activities are discussed. Cost-to-benefit ratios for in-house and outsourced activities, while still enabling an aggressive fast-to-licensure timeline to bring urgent therapies to patients, are also covered.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing\


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10:45 Plasmid DNA Topology and Triple Transfection rAAV Production

Thompson_LawrenceLawrence Thompson, PhD, Principal Scientist, Analytical Research & Development, BioTherapeutics Pharm Sciences, Pfizer

Current regulatory guidance suggests that some measure of plasmid DNA potency be captured in the analytical control strategy. For plasmid DNA used in triple transfection rAAV production, this can only be described as attributes of said plasmid that, when controlled, are able to produce rAAV of the appropriate quantity and quality. This presentation is a case study that will pressure test plasmid DNA topology as one of those attributes.

11:15 A Digestion-Free Method for Residual DNA Quantification in rAAV Vectors

Wang_YuYu Wang, PhD, Scientist II, Analytical Development, Biogen

The existing methods for residual DNA quantification in rAAV require digestion of capsid proteins by proteinase. We have developed a digestion-free method that significantly simplifies sample preparation and shortens assay time. The method has been verified by qPCR, as well as the more recent ddPCR technology for quantification of residual host cell or plasmid DNA in varies of AAV serotypes.

11:45 Meaningful Analytics Data for Quick Decision Making in Development of Viral Vector-Based Therapies

Carvalho_VanessaVanessa Carvalho, Senior Scientist, EM Services, Vironova

12:15 pm Enjoy Lunch on Your Own

1:00 Dessert Break in the Exhibit Hall with Poster Viewing


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1:45 Chairperson’s Remarks

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

1:50 Strategies and Advances in AAV Vector Characterization: Product-Related Impurities

Christine_LeBecChristine Le Bec, PhD, Head, CMC Analytical, Technology Development, Genethon

Selected analytical assays were developed to assess the vector productivity, vector purity, biological activity/potency. The quantitative PCR (qPCR) is the current gold method of titrating AAV genomes. The Droplet Digital PCR (ddPCR), a new technology which has been designed for accurate DNA quantification, could improve titer determination. Comparison between these two methods will be discussed. The presentation will also cover methods to determine the ratio of full/empty viral capsids.

2:20 Comparative Studies on the Empty/Full AAV Capsid Using Multiple Analytical Methods

Dong_XuDong Xu, PhD, Senior Scientist, Analytical Development, Biogen, Inc.

For AAV-delivered gene therapy, the percentage of full viral capsid is an important product quality that needs to be quantitatively characterized. We have used several analytical tools to investigate the ratio of empty to full capsid ratio, including HPLC, CE, AUC, PCR, TEM and Mass Spectrometry. The comparison of these results reveals to us the advantages and limitations of each method in industrial applications.

2:50 Phase-Appropriate Potency Assays for AAV Gene Therapy Products

McColl-Carboni_AisleenAisleen McColl-Carboni, PhD, Senior Scientist, Analytical Development, Sanofi

AAV gene therapy products have complex mechanisms of action that pose unique challenges to potency assay development. Determining the true biological activity often requires multiple assays (i.e. a matrix approach), and the strategy for implementing these assays may evolve through the product lifecycle. This presentation will discuss phase-appropriate development and qualification of different in vitro potency assays.

3:20 Development of a High-Content Imaging Potency Assay to Support a Manufacturing Platform

Leyme_AnthonyAnthony Leyme, PhD, Scientist II, Technical Development, Analytical Bioassay Development, Biogen

AAV-based vectors represent a new type of drugs being developed for gene delivery in different therapeutic areas. Biological assays are required to assess vector quality, biological activity and safety. Potency of the drug is the most critical quality attribute, it must be specific, quantitative, and ideally reflective of the mechanism of action. This presentation will focus on the development of a high-content imaging potency assay to support a manufacturing platform.

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


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8:25 Chairperson’s Remarks

Wei-Chiang Chen, PhD, Senior Scientist, Analytical, Flexion Therapeutics

8:30 Material Identity Testing for Manufacturing of Gene Therapy Products in an Academic Setting

Van_Zalen_SebastiaanSebastiaan Van Zalen, PhD, Quality Manager, Clinical Vector Core, Children’s Hospital of Philadelphia

Identity testing of raw materials used for manufacturing of investigational gene therapy drugs poses several challenges. We will discuss which of the available techniques would be most suitable and what adaptations and methods can be developed to help identify these raw materials. We will also address how to comply with the increasing regulatory requirements in an academic setting in which the composition of the materials varies for each product lot.

9:00 An Approach to Developing Analytical Testing and Release Plans for AAV Gene Therapy Vectors

Higgins_ElizabethElizabeth Higgins, PhD, Director, Analytical Sciences, Voyager Therapeutics, Inc.

A suite of analytical tests is critical to support product characterization, process development, stability and batch release of AAV gene-therapy products. The selection of assays is driven by the development stage of the program, the transgene and the manufacturing process. This presentation will describe the approach that Voyager has taken, including platform analytical methods to support multiple programs, leveraging assays used for therapeutic proteins and developing specific potency assays.

9:30 Encapsidated rAAV Genome Characterization by Next-Generation Sequencing

Hui-wen Liu, PhD, Scientist I, Analytical Development, Biogen

9:45 Potency Assay Development for rAAV Vector Encoding ATP Binding Cassette Subfamily D Member 1 Protein (ALDP)

Geeta Iyer, Research Associate II, AGTC

10:00 Coffee Break in the Exhibit Hall with Poster Viewing


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10:45 Determining the Total Particle Titer of AAV by Multi Angle Dynamic Light Scattering

Julie Wei, PhD., Analytical Development, Ultragenyx

AAV capsid titers define the patient exposure to the therapies, and are typically determined by commercial ELISA assays. ELISA-based capsid titer assays tend to have poor accuracy due to the lack of well-characterized reference materials. Quantifying total particles by Multi Angle Dynamic Light Scattering is an orthogonal way to directly determine AAV capsid titers. This presentation will cover the method development and provide comparison between different capsid titer methods.

11:15 Improving Viral Manufacture through Advanced Process Analytical Technologies

Marshall_DamianDamian Marshall, PhD, Director, New Technologies, Cell & Gene Therapy Catapult UK

Developing manufacturing strategies which can service the growing global demand for high quality viral vectors is a significant challenge. This is creating an industry pull for more advanced process control and smarter manufacturing technologies. This presentation will present new data on the application of optical biosensors for in-process monitoring and look at the potential role that artificial intelligence could play in supporting future viral vector production.

11:45 Panel Discussion: Analytical Strategies for Gene Therapies


Wei-Chiang Chen, PhD, Senior Scientist, Analytical, Flexion Therapeutics


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

Bo Yan, PhD, Senior Scientist, Analytical Development, Beam Therapeutics

Damian Marshall, PhD, Director, New Technologies, Cell & Gene Therapy Catapult UK

Sarah Sullivan, PhD., Scientist I, Technical Development, Biogen

  • What are the best tools to characterize AAV and lenti-based gene therapies – MS, NMR, HPLC
  • Assay and potency assay development for gene therapies
  • In vivo tests, molecular tests and profiling
  • Stability indicating assays

12:15 pm Enjoy Lunch on Your Own

1:15 Refreshment Break in the Exhibit Hall with Last Chance for Poster Viewing 

1:55 End of Conference