Cambridge Healthtech Institute ’s 2nd Annual

Gene Therapy CMC and Manufacturing

Ensuring the Analysis, Production and Quality of Viral Vectors

New Dates - 22-23 JULY 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, 22 July

10:40 Chairperson’s Opening Remarks

Christine Le Bec, PhD, Head, CMC Gene Therapy, Sensorion


10:45 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.

11:05 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.

11:25 Optimizing CAR-T Process Development by Utilizing a Novel Small Scale Stirred Tank BioreactorSartorius_NEW


Maya Fuerstenau-Sharp, PhD, Regenerative Medicines, Sartorius Stedim Biotech 
Currently, static and shake flasks for suspension processes are widely used in the process development of advanced therapies. However, these cell expansion approaches are labor-intensive and require a high level of highly skilled operator manipulation and offer only a low level of cell culture monitoring and control.  Here we demonstrate the utility of the ambr250 modular and the newly designed unbaffled single impeller vessel as a process evaluation tool for the expansion of CAR-T cells.   

12:00 Lunch Break - Come view our virtual Exhibit Hall



12:25 Chairperson’s Remarks

To be Confirmed

12:30 Continuous Processing for Vaccine Manufacturing: Challenges and Opportunities

Yang-PingYangYan-Ping Yang, PhD, Head of Bioprocess Research & Development, North America, Sanofi Pasteur

Over the last decade, there have been significant investments in continuous manufacturing in the pharmaceutical industry, as it holds great promise to lead the reduction of process steps, smaller footprint, higher product quality, and better pharmaceuticals for patients. While it’s still in its early stage, the vaccine industry has embraced this concept and is ready to explore the full advantages associated with this approach. This presentation explores the challenges and opportunities to make continuous vaccine manufacturing a reality.

12:55 Gene Therapy Manufacturing and Technical Development

Blumenthal_DianeDiane 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.

13:20 Q&A, Session Wrap-up, Host intro to special virtual features


13:35 Break Time to view virtual Exhibit Hall

13:55 Chairperson’s Remarks


Christine Le Bec, PhD, Head, CMC Gene Therapy, Sensorion

14:00 Phase-Appropriate Potency Assay Development for Gene Therapy Products

Laura Geagan, PhD, Principle 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.

14:20 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.

14:40 Sponsor Presentation (Opportunity Available)          

15:00 Q&A, Session Wrap-up

15:15 Virtual Happy Hour in our Virtual Exhibit Hall


Thursday, 23 july

8:00 Registration and Morning Coffee


9:00 Chairperson’s Remarks

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

9:05 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.

9:25 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.

9:45 Morphology, Purity and Integrity of Viral Vector-based TherapiesVironova

Vanessa Carvahlo, PhD, Senior Scientist, Electron Microscopy Services, Vironova

Viral vector-based therapies are on the rise in the biopharma industry. During the development of viral vectors, it is critical to have access to accurate analytical data that provides the highest amount of information possible about the process but also about the sample itself. Transmission electron microscopy (TEM) is a high-resolution image technique. The power of this technique allied with the neural network imaging processing tools grants the detection and classification of a wide range of particles. In the field of the gene therapy and vaccine development it is crucial to have a broad portfolio of analytical tools. TEM is one of these valuable tools, allowing a direct visualization of the sample in the tube. A TEM image and its analysis will give essential information regarding morphology, integrity and purity of the samples. The description of this characteristics can often be directly correlated with the efficacy and safety of the product before administrated in the patient. In this presentation we will illustrate the potential of TEM in combination with image analysis and how the portfolio of instruments, software and services from Vironova, AB can contribute to fact-based decision making in viral vector processes.

10:05 Q&A, Session Wrap-up

10:20 Break Time to View our Virtual Exhibit Hall

10:45 Chairperson’s Remarks

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

10:50 Strategies and Advances in AAV Vector Characterization: Product-Related Impurities

Christine_LeBecChristine Le Bec, PhD, Head, CMC Gene Therapy, Sensorion

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.

11:10 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.

11:30 Quantification of Viral and Non-viral Vector CQAsWyatt-logo-New-Logo-only

Some Dan

Dan Some, PhD, Marketing, Wyatt Technology Corp.

Reliable biophysical characterization is a central challenge in development of gene therapies. Robust analytical tools based on light scattering, essential in the development and commercialization of monoclonal antibodies and virus-based vaccines, are also suitable for gene vectors, whether viral or non-viral. This talk will highlight the applications of multi-angle and dynamic light scattering for the determination of critical quality attributes of gene vectors including among others analysis of AAVs, lentiviral vectors and synthetic vectors.  

11:50 Q&A, Session Wrap-up

12:05 Lunch Break - Come View our Virtual Exhibit Hall


12:30 Chairperson’s Remarks

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

12:35 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.

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