Cambridge Healthtech Institute ’s 2nd Annual

Gene Therapy CMC and Manufacturing

Ensuring the Supply and Quality of Viral Vectors

25-26 March 2020


Robust and cost-effective viral vector characterization and manufacturing presents a core challenge in the commercialization of gene therapies with pressure mounting on CMC, analytical and manufacturing teams to keep up with accelerated development times and cost pressures.

CHI's Gene Therapy CMC and Manufacturing conference examines the critical challenges facing the production, characterization and quality control of vector-based gene therapies, with dedicated sessions on rapid CMC development, product and process characterization, upstream and downstream bioprocessing and considerations for large-scale manufacturing.

Final Agenda

Wednesday, 25 March

10:30 Registration

10:30 Coffee Break in the Exhibit Hall with Poster Viewing



11:15 Chairperson’s Remarks

Jarka Glassey, PhD, Professor, Chemical Engineering, Engineering, Newcastle University

11:20 Current Opportunities and Challenges in Biotherapeutic CMC

Schumacher_RalfRalf Schumacher, PhD, Global Head, Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG

As biologic pipelines continue to grow and diversify, there is an increasing need to standardize, automate and find efficiencies along the entire value chain. This presentation will discuss the current challenges and opportunities in biotherapeutic CMC and the impact new modalities are having on upstream and downstream processing, analytics and formulation. The advantages of predictive process parameters in early stage development and digital development concepts to speed up the CMC development will also be discussed.

11:50 Gene Therapy Manufacturing and Technical Development

Diane_BlumenthaDiane Blumenthal, PhD, Head, Technical Development, Spark Therapeutics

In the past few years, several cell and gene therapy products have gained regulatory approval in the US and EU with many more in the pipeline. Manufacturers of cell and gene therapy products must tackle technological challenges under the pressure of short timelines resulting from streamlined clinical development. This presentation will focus on the key technical development challenges facing the industry as product development programs move the into the later stages of process development and scale-up, process performance qualification and ultimately commercialization.

12:20 Session Break

12:30 Bridging Luncheon Presentation: To be Announced

13:00 Session Break


13:45 Chairperson’s Opening Remarks

Christine Le Bec, PhD, Head of CMC Analytical, Technology Development, Genethon

13:50 Analytical Challenges for Gene Therapy

Clare_BlueClare Blue, PhD, Director, Analytical Development, Biogen

One of the biggest challenges for AAV gene therapy products is establishing an appropriate analytical strategy to support product manufacture, release, stability, comparability and characterization at different stages of development. This presentation will highlight some of the existing analytical challenges and provide guidance on development of an appropriate strategy to help overcome these.

14:20 Phase-Appropriate Potency Assay Development for Gene Therapy Products

Francis_PoulinFrancis Poulin, PhD, Director, 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.

14:50 KEYNOTE PRESENTATION: Rapid CMC Development and Pre-Commercial Considerations for rAAV Gene Therapy Products for Rare Diseases

James Warren, PhD, Vice President, Pharmaceutical Development, Ultragenyx

Ultragenyx has established a fast-to-clinic CMC development strategy leveraging two distinct production platforms, implementation of high-throughput centers of excellence, and a state-of-the-art pilot plant to streamline and standardize the development and technology transfer of preclinical and clinical candidates. Process development has resulted in significant volumetric productivity increase and improvement in yield across chromatography and filtration steps. Scalability of new products to 250L has been demonstrated within 3 months.

15:20 Presentation to be Announced

15:50 Refreshment Break in the Exhibit Hall with Poster Viewing

16:25 Relative vs. Absolute Quantification of Purified and In-Process rAAV Productions

Pytel_KamilaKamila Pytel, PhD, Lead, CMC Analytical Development, Gyroscope Therapeutics Ltd.

Gene therapy delivery of a drug product requires precise determination of vector titre by a suitably qualified analytical method. Despite the importance of titre assays for product release, optimisation of R&D methods is also crucial to allow for better understanding of the changes in rAAV titre and yield from upstream to downstream unit operations. qPCR is widely considered the gold standard for this purpose. In addition, we adopted orthogonal analytical tools including ddPCR and HPLC as robust and rapid titration alternatives to qPCR.

16:55 Strategies and Advances in AAV Vector Characterization: Product-Related Impurities

Christine_LeBecChristine Le Bec, PhD, Head of 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.

17:25 CMC Development at MeriaGTX

Griffith_AlanAlan Griffiths, PhD, Director, Viral Vector Development, MeriaGTX

17:55 End of Day

18:00 Dinner Short Course Registration

Recommended Dinner Short Course*

18:30 - 21:00 SC4: Quality Considerations for Gene Therapy Viral Vectors

Instructor: Christopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals Ltd.

*Separate registration required.

Thursday, 26 March

8:00 Registration and Morning Coffee


8:25 Chairperson’s Remarks

James Warren, PhD, Vice President, Pharmaceutical Development, Ultragenyx

8:30 HEK293 Cell Adaptation to New Media and Use of New DoE Approach to Optimize AAV Production in Suspension Utilizing the ambr®15 Platform

Eduard_AyusoEduard Ayuso, DVM, PhD, Team Leader, Innovative Vectorology; Scientific Director Translational Vector Core (CPV), Translational Gene Therapy for Genetic Disorders, Inserm, University of Nantes

A major bottleneck of gene therapy is the large-scale manufacturing of viral vectors. The most common platform for producing AAV is the transient transfection of adherent HEK293 cells, however, suspension cultures are easy to scale up. Here, we used Sartorius ambr15 system to adapt two HEK293 cell lines into 7 media and to screen transfection conditions in suspension using DoE with the MODDE® software to maximize AAV productivity.

9:00 Droplet Digital PCR – State of the Art Vector Genome Titering or Even More?

Pletzenauer_RobertRobert Pletzenauer, Head, Process Analytics, Takeda Gene Therapy Process Development

Droplet digital PCR is a powerful technique, which allows vector genome titer quantification without the necessity of a reference. In this talk, the benefits, like an enhanced precision compared to RT qPCR, the power of absolute quantification but also potential drawbacks of this innovative technique will be in the focus. Moreover, different strategies of designing the transgene target sequences and the individual influence on the obtained results will be discussed.

9:30 Viral Vector Smart Processing

Gregory_BergerGregory Berger, PhD, Lead Scientist, Cell and Gene Therapy Catapult

Viral vector processing at scale requires a high level of control which can be achieved via the introduction of PAT. This presentation will present a case study of successful PAT implementation within the viral vector space to drive both process intensification and increase process robustness.

10:00 Presentation to be Announced

10:30 Coffee Break in the Exhibit Hall. Last Chance for Poster Viewing.

11:15 AAV Manufacturing: Early Development to Long-Term Manufacturing Strategies

Jean_Philippe_CombalJean-Philippe Combal, PhD, Co-Founder and CEO, Vivet Therapeutics

AAV manufacturing is often identified as one product is one process. Although comparability data may overcome change in process, some significant uncertainties will remain from early process development to commercial scale. As small or big biotech we may not have the means to start with a scalable process and therefore strategic scenario to control our destiny.

11:45 Challenges in Process Scale-Up with 500 L Scale Manufacturing of AAV

Marian_BendikMarian Bendik, PhD, Site Lead Orth, Gene Therapy Center Austria, Biologics Operating Unit, Technical Operations, Takeda

The presentation will provide an overview of major manufacturing challenges associated with process scale-up of transient HEK293 transfection together with downstream pitfalls. Further, it will sum up 3 years of manufacturing experience in AAV 500 L scale. What are unknown unknowns?

12:15 Vector Design and Production Scale-Up of AAV-Based Gene Therapies for Inflammatory Disease

Janneke_MeulenbergJanneke Meulenberg, PhD, MBA, COO, Arthrogen

Arthrogen is developing local gene therapy for inflammatory diseases, using viral mediated gene transfer. Arthrogen’s first product that has been tested in clinical trials is an AAV5-based vector expressing interferon beta from an inflammation inducible promoter. This vector was produced using classical plasmid transfection in adherent cells. Arthrogen is currently evaluating different scalable systems for future AAV production runs. The pros and cons of these systems and the consequences for product characterization and quality control will be discussed.

12:45 Luncheon Presentation to be AnnouncedWyatt-logo-New-Logo-only

13:30 Session Break


13:45 Chairperson’s Remarks

James Warren, PhD, Vice President, Pharmaceutical Development, Ultragenyx

13:50 Development of a Robust Purification Process for Adeno-Associated Virus

Roach_MatthewMatthew Roach, Process Development Engineer, Precision Biosciences

The purification of adeno-associated virus has become an increasingly important topic in the field of biomanufacturing as the prevalence of AAV gene therapies increases. One of the major hurdles facing AAV purification is the separation of empty capsids from full capsids. This presentation will address Precision BioSciences’ advances in downstream chromatography for both capture and empty full separation steps.

14:20 Enabling Lentiviral Vector Manufacturing: Identifying Producer Cell Bottlenecks to High Titers

Ana_Sofia_CoroadinhaAna Sofia Coroadinha, PhD, Lab Head, Health & Pharma Division, Animal Cell Technology Unit Cell Line Development and Molecular Biotechnology Lab, IBET

Lentiviral vector manufacturing is transitioning from transient to stable production systems. The establishment of stable producer cell lines has been a challenge due to the cytotoxicity of the vector. This work presents strategies enabling the generation of constitutive lentiviral cell lines showing sustained production over 1 week which supports effective upstream processes. Detailed characterization of producer cell clones was performed revealing critical parameters.

14:50 Generation of Packaging Cells for Lentiviral Vectors Using Nanowell-Based Single-Cell Cloning Technology

Gilbert_RénaldRénald Gilbert, PhD, Team Lead, Department of Bioprocess Engineering, NRC Canada

In this presentation I will describe our approach to generate packaging cells for lentiviral vectors. The approach entails the generation of pools that are cloned by limiting dilution into nanowells and isolation with a robotic cell picker. I will also provide examples of process development using producer clones derived from our packaging cells to increase the yield of vectors in serum-free suspension culture.

15:20 Close of Summit

* The program is subject to change without notice, due to unforeseen reason.

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