Cambridge Healthtech Institute ’s Inaugural

Gene Therapy CMC and Manufacturing

20-21 March 2019


The vector-based gene therapy industry has undergone rapid advances over the last twelve months and shows no sign of slowing down. The clinical results are beyond encouraging. However, the pressure is now on CMC, analytical, process development and manufacturing department to produce these therapies at scale.  

The Gene Therapy CMC and Bioproduction conference examines the practical challenges facing the production, characterization and quality control of vector-based gene therapies, with dedicated sessions on AAV and lentivirus-based platforms as well as oncolytic viruses, CRISPR and other gene editing therapies. Topics include new and emerging analytical strategies, upcoming regulations and the latest manufacturing strategies for large- and small-scale production.

FInal Agenda

Wednesday, 20 March

10:00 Registration Open

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


11:15 Chairperson’s Remarks

Manuel Carrondo, PhD, Professor of Chemical and Biochemical Engineering, FCT-UNL; Vice President, IBET


11:20 Bioprocessing Innovations in the Era of Clinical Acceleration and Process Intensification

Stefanos Grammatikos, PhD, Vice President, Head, Biotech Sciences, UCB Pharma

Current trends in clinical development acceleration and bioprocess intensification impose an unprecedented compression of CMC development timelines and new bioprocessing challenges downstream of the cell culture bioreactor. In this talk I will present a series of innovations we have introduced, some incremental and some potentially disruptive, in an effort to avoid further complications while rising to the latest challenges of bio CMC development and bioprocessing.

11:50 Opportunities and Challenges in CAR T Manufacturing

Markwin Velders, PhD, Vice President, Operations, Managing Director, Kite Pharma EU B.V.

Update on the status of CAR-T development for use in the treatment of cancer. The success story of this paradigm shift and the challenges and opportunities that lay ahead for this therapy will be presented and discussed.

12:20 Session Break

12:30 Bridging Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:00 Session Break


13:40 Chairperson’s Opening Remarks

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





13:45 KEYNOTE PRESENTATION: LUXTURNA (voretigene neparvovec): From Clinical Development to FDA Approval

Dan Takefman, PhD, Head, Regulatory Affairs, Spark Therapeutics






14:15 Viral Vector Manufacturing and Control: Regulatory Considerations and Challenges

Matthias_RennerMatthias Renner, PhD, Scientist, Federal Institute for Vaccines and Biomedicines, Paul Ehrlich Institute

In respect to manufacturing and quality control, viral vectors are considered to be one of the most complex medicinal products. Regulatory aspects considering the fundamental steps in manufacturing and control of these medicinal products will be presented, and the regulatory framework for these products which are classified in the EU as advanced therapy medicinal products and are regulated centrally by the European Commission and the European Medicines Agency will be given.

14:45 Analytics for AAV-Based Gene Therapy Products

Francis_PoulinFrancis Poulin, PhD, Director, Analytical, Sanofi

Health authorities emphasize the importance of employing suitable dose-determining methods for gene therapy products. We will discuss the analysis and characterization methods employed to support gene therapy projects. This presentation spans method development through qualification and illustrates the benefits of comparing platforms early in product development.

15:15 Analysis of Purity and Packaging of Gene Therapy Vectors and VLPs to Support Process Development Decisions

Josefina Nilsson, Head, EM services, Electron microscopy services, Vironova

Challenges with scale up of gene therapy processes include surprises in purity profiles. Robust analytical solutions are required to avoid late surprises. Transmission electron microscopy (TEM) provide unmatched insights in characterization of viral gene vectors. MiniTEM automatically provides: Comparative metrics on purity profiles of viral particle samples Automatically differentiates intact viral particles from process related impurities Correlation between potency and viral particle morphology.

15:45 Refreshment Break in the Exhibit Hall with Poster Viewing

16:25 Analytical Approaches to Characterize AAV Gene Therapy Products

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

In recent years, AAV vectors have been increasingly evaluated in various gene therapy clinical trials. To sustain this, reliable, fast, robust, GMP compliant analytical methods and characterization protocols are needed. Specific analytical assays were performed to assess vector productivity, vector purity, potency and safety. I will present different methods to quantify host cell DNA and host cell protein to support the process development and characterize preclinical and clinical lots.

16:55 Looking at the AAV Particles from Inside and Outside Using Novel Analytical Tools

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

Our laboratory has been deeply involved in the harmonization of adeno-associated viral vector (AAV) characterization through the international reference standard efforts and has developed novel protocols for accurate titration of these vectors. Moreover, recent analytical tools based on next generation sequencing technologies, allowed us to identify and quantify residual DNA species in vectors produced in mammalian and insect cells. More recently, we have detected the presence of miRNA in the final product (i.e. after purification) of AAV vectors. Our examples show that it is crucial to push vector analytics forward to drive innovation in manufacturing processes and vector design.

17:25 Creating Sustainable Process Development Strategies for Gene Therapy Products

Barbara Kraus, PhD, Head, Gene Therapy Process Development and Technical Services, Shire

17:55 End of Day

18:00 Dinner Short Course Registration

18:30 - 21:00 Recommended Short Course*

SC4: CMC Clinic: Where Am I Now and Where Do I Need to Be with My Dossier


Christopher_BraveryChristopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals, Ltd.

Share your problems at the CMC regulatory clinic, learn how others have addressed them and gain new insights into what regulators are looking for. Puzzled by how to structure your dossier? Unsure if you have enough data for your next clinical trial application? Wondering how much data will be needed for approval? When does a problem need to be discussed with regulators and how should you approach them?

*Separate registration required.

Thursday, 21 March

8:00 Registration and Morning Coffee

Manufacturing Viral Vectors at Scale

8:25 Chairperson’s Opening Remarks

Mercedes-SeguraMercedes Segura, PhD, Director, Next Generation Platforms and Technologies, bluebird bio




8:30 FEATURED PRESENTATION: 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, Shire

The presentation will provide 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?

9:00 Process Development Strategies: Academic to CMO vs. Integrated

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

Vivet Therapeutics is a gene therapy company dedicated to the development of gene therapy treatments for inherited liver disorders with high unmet medical need. The company’s development strategy is to target the liver with a novel synthetic adeno associated virus (AAV-Anc80) to introduce therapeutic genes to hepatocytes. This presentation will discuss the internal vs. external manufacturing decisions gene therapy companies have to make on the road to commercialization.

9:30 Sponsored Presentation (Opportunity Available)

10:00 Process Development Approaches for AAV Gene Therapy Products

Matthias_HebbenMatthias Hebben, PhD, Gene Therapy Technology and CMC Development, Genethon

In recent years, AAV vectors have been increasingly evaluated in various gene therapy clinical trials. To sustain this, reliable, fast, robust, GMP compliant process development strategies are needed. I will present the technologies, tools and strategies employed during process development and scale up for an internal project.

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

11:15 Process Development Challenges in Gene Therapy Moving from Early Clinical to Late Phase/Commercial

Tarik_SenussiTarik Senussi, Head, Process Development, Gyroscope Therapeutics

Material to supply initial clinical studies is often delivered via early stage contract manufacturing organisations to clinical phase appropriate regulatory standards. This inevitably requires subsequent modification and transfer to a facility that can support late stage and commercial manufacture as the product progresses through development. This talk will cover the opportunities and challenges associated with this transition, considering robustness, yield and comparability.

11:45 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.

12:15 Manufacturing Strategies and Regulatory Considerations for mRNA Therapeutics

Andreas_KuhnAndreas Kuhn, Vice President, RNA Biochemistry & Manufacturing, BioNTech RNA Pharmaceuticals GmbH

Messenger (m)RNA is increasingly investigated as a platform technology for multiple therapeutic applications. This approach is most advanced in the context of immunotherapies against cancer, but is in general applicable whenever expression of a protein is desired. In my talk I will present the advantages and challenges for manufacturing mRNA for clinical studies. In addition, I will discuss regulatory considerations with respect to the classification of mRNA as gene therapy by both FDA and EMA.

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:15 Session Break


13:45 Chairperson’s Remarks

Mercedes Segura, PhD, Director, Next Generation Platforms and Technologies, bluebird bio

13:50 Bioprocessing Strategies for Gene Therapies

Mercedes-SeguraMercedes Segura, PhD, Director, Next Generation Platforms and Technologies, bluebird bio




14:20 Lentipro Stable Producer Cells for the Development of Scalable Lentiviral Vector Manufacturing

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

This work discusses the challenges in lentiviral vector manufacture and scale-up as well the strategies and novel technologies to be adopted to enable effective upstream processes. At upstream, many of the challenges are related to the vector cytotoxicity, restricting the bioreaction to short-term productions. Thus, one of our strategies is to reduce vector cytotoxicity which enabled to establish lentiviral vector producer cell lines constitutively producing infective virus over 1 week.

14:50 Lentiviral Vector Manufacturing - Problem or Not?

Hanna_LeschHanna Lesch, PhD, Director, Gene Therapy Unit, Kuopio Center for Gene and Cell Therapy

There are very few lentivirus success stories. Partially that has been explained because of the manufacturing issues. Is it still today a problem or are there solutions available? The talk will cover the main challenges, case study of process development and scale-up of lentivirus manufacturing into iCELLis500 and will dive into the future visions and possibilities.

15:20 Close of Conference