Cambridge Healthtech Institute’s 4th Annual

Gene Therapy Manufacturing
( 基因療法藥物的製造 )

Production Strategies for Vector-Based Gene Therapies


It is an exciting time for gene therapy – therapies on the market, strong investment and encouraging clinical data – but manufacturing still represents one of the major stumbling blocks to successful commercialization.

Cambridge Healthtech Institute’s Gene Therapy Manufacturing conference takes a practical, case-study driven approach to the process development, scale-up and production of gene therapies, tackling key topics such as AAV, lentivirus and retrovirus process development and scale-up, CMO management from early to late-stage development.

Final Agenda


11:30 am Registration Open

12:15 pm Enjoy Lunch on Your Own

1:15 Refreshment Break in the Exhibit Hall with Last Chance for Poster Viewing (Sponsorship Opportunity Available)


1:55 Chairperson’s Remarks

John Pieracci, PhD, Director, Purification, Biogen

2:00 KEYNOTE PRESENTATION: Present and Future of AAV Gene Therapy Technical Development and Manufacturing

Maranga_LuisLuis Maranga, PhD, Chief Technical Operations Officer, Voyager Therapeutics, Inc.

Recombinant AAV is coming of age as a gene therapy vector of choice. Nevertheless, development and manufacturing for AAV is still in its infancy, and, similarly to the evolution of protein biologics in the last 3 decades of the past century, multiple expressions systems and production technologies are still being employed. The current state of technologies for AAV production and how emerging trends will force their evolution will be discussed.

2:45 FEATURED PRESENTATION: Development, Optimization and Technology Transfer of the Scalable Pro10TM rAAV Manufacturing Process

Grieger_JoshJosh Grieger, PhD, CTO, Asklepios BioPharmaceutical

Over a decade ago, we successfully adapted an adherent HEK293 cell line from a qualified clinical master cell bank to grow in animal component-free suspension conditions in shaker flasks, WAVE and stir tank bioreactors allowing for rapid and scalable rAAV production at >250L scale. My presentation will focus on the optimization, technology transfer (2 Pharmaceutical companies and Viralgen) and GMP manufacturing of rAAV vectors utilizing the Pro10 manufacturing process.

3:15 Evolution of a Platform Process Across Clinical Manufacturing

Horvath_JustinJustin Horvath, PhD, Director, Manufacturing, Regenxbio

Pall_Biotech3:45 Presentation to be Announced

4:00 Refreshment Break

4:15 rAAV Vector Design, Capsid Directed Evolution and Scale Up Activities Using the BEVS System

Lubelski_JacekJacek Lubelski, PhD, Vice President, Global Pharmaceutical Development, uniQure

Scaling up of rAAV manufacturing process displays various challenges, one of which is the variability introduced by starting and raw materials. I will discuss our effort to limit the sensitivity of uniQure’s rAAV production system to fluctuation in input materials, and present our experience with baculoviruses/insect cell system in stirred tank bioreactor and our efforts to make stronger and more specific promoters. Finally, I will discuss the vector quality and potency generated by insect and mammalian cell production systems.

4:45 AAV Upstream Production Process Optimization for the Sf9/Baculovirus System

Slade_PeterPeter Slade, PhD, Director, Cell Culture, Voyager Therapeutics

5:15 End of Day


7:30 am Registration Open

7:30 Small-Group Breakout Discussions with Continental Breakfast

This session provides the 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.


8:30 Chairperson’s Remarks

Johannes C.M. van der Loo, PhD, Director, Clinical Vector Core, The Raymond G. Perelman Center for Molecular and Cellular Therapies, Children’s Hospital of Philadelphia

8:35 Optimization of Transfection and Culture Conditions to Maximize AAV Production in Suspension 293-Based Cells

Piras_BryanBryan Piras, PhD, Lead Scientist, Process Development, Therapeutics Production and Quality, St. Jude Children’s Research Hospital

Production of AAV for early-phase clinical use requires manufacture utilizing hundreds of liters of upstream cell culture. Production facilities for early-phase trials have often relied upon adherent cell-based processes, though suspension cells offer greater flexibility and far superior scalability. We have identified a variety of transfection and culture conditions to help maximize production of an AAV8 vector in 293-based suspension cells.

9:05 Viral Vector Bioprocessing at the National Research Council Canada

Mullick_AlakaAlaka Mullick, PhD, Senior Research Officer, National Research Council Canada

In this presentation, we will summarize expertise in viral vector bioprocessing at NRC. We will focus on strategies that we have developed using our proprietary HEK293SF suspension cell line platform for lentiviral and adeno-associated viral vector (LV, AAV) bioprocessing. We will use case studies to illustrate our progress in these areas, such as development of stable inducible packaging and producer cell lines for LV and scalable workflows for AAV manufacturing.

9:35 AAV Vectors: From Discovery to Large-Scale Clinical Manufacturing: An Academic Success Story

Clement_NathalieNathalie Clément, PhD, Associate Director and Associate Professor, Powell Gene Therapy Center, Pediatrics, University of Florida

The talk will present our current methods for the production of research and clinical-grade rAAV with a special emphasis on the HSV-based suspension method capable of generating high titers of improved rAAV quality. Up-to-date in vitro, in vivo, and clinical data will be shown, and pros and cons of the method will be discussed in comparison to the two other most common methods, transfection and the baculovirus system.

10:05 Networking Coffee Break


10:30 Implementing Commercial Ready Processes for Clinical Applications

Dobrowsky_TerrenceTerrence Dobrowsky, PhD, Principal Engineer, Gene Therapy, Biogen

Implementing commercial ready processes early in the development of gene therapy products eliminates scalability and comparability issues later in the product lifecycle. Here we will review development to-date as well as strategies for leveraging both transient transfection and producer cell line (PCL) production systems to quickly establish scalable, manufacturing ready processes at Biogen. This development work includes improvements to cell line and vector generation workflows, shifting from adherent to suspension cell culture systems, media & feed development as well as process steps that are linearly scalable.

11:00 Technology Transfer of an Academic Hematopoietic Stem Cell Gene Therapy Manufacture to Industry: The Mustang Bio X-SCID Experience

Greene_MichaelMichael Greene, MD, Executive Director, Technology Transfer Lead, Mustang Bio, Inc.

Mustang Bio, Inc., a Fortress Biotech Company, has partnered with St. Jude Children’s Hospital to manufacture MB-107, a cell and gene therapeutic to treat the devastating orphan disease X-linked severe combined immunodeficiency (X-SCID). We will present our experience during the technology transfer of an academic manufacturing process to industry.

11:30 Virus Clearance Strategy for AAV Producer Cell Line Process: A Case Study

Morais_JasonJason Morais, DSP Lead, Gene Therapy Development, Sanofi

Wild-type Adenovirus can be used as a ‘helper virus’ to initiate replication of recombinant AAV in producer cells. However, during production, Adenovirus is replicated alongside AAV and is present as a process-related impurity. This Adenovirus must be removed and/or inactivated during purification in order to ensure patient safety. Here we present a virus validation study conducted on an AAV purification process, confirming greater than 20 LRV of Adenovirus reduction.

Fujifilm-Diosynth-Logo 12:00 pm Presentation to be Announced

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

1:15 Session Break


1:25 Chairperson’s Remarks

Nathalie Clément, PhD, Associate Director and Associate Professor, Powell Gene Therapy Center, Pediatrics, University of Florida

1:30 Development of an Advance AAV Purification Platform Using Integrated Analytics and PAT

Leseigneur_FlorianFlorian Leseigneur, PhD, Viral Vector Development Team, Cell and Gene Therapy Catapult

Traditional AAV manufacturing downstream processes are based upon non-scalable techniques which involve multiple steps and rely on time consuming offline analytical techniques for evaluation. As demand for AAV increases there is a pressing need for simplified viral vector purification trains with real-time titre, quality and purity measurements. Here, we will present an AAV purification platform with integrated analytics and PAT sensor technologies which allows rapid product characterisation

2:00 Chromatography Beads, Monoliths or Membrane Absorbers for Purification of Gene Therapy Vehicles and Bionanoparticles

Jungbauer_AloisAlois Jungbauer, PhD, Professor, Institute of Biotechnology, University of Natural Resources and Life Sciences (BOKU)

Heterogeneous populations of bionanoparticles such as viruses, virus-like particles, or other extra cellular bionanoparticles in gene-therapy or in cancer therapy are released from the cells, carrying different host cell proteins, DNA and RNA fragments. Here we compare the results obtained for the purification particle populations’ separation of bionanoparticles produced in CHO cell culture using different downstream processing approaches. These approaches include polymer grafted anion exchangers, monoliths (anion exchange and hydrophobic interaction), a combination of flow-through and heparin affinity chromatography, and membrane adsorbers.

2:30 Development of High-Throughput Purification Methods for AAV

Roach_MatthewMatthew Kevin Roach, PhD, Senior Associate Scientist, Gene Therapy Process Development, Pfizer

Smart and efficient approaches for lab-scale purification are required to ensure a robust adeno-associated manufacturing process. This talk will describe the development of a high throughput purification method for an AAV manufacturing process and the challenges involved.

3:00 Application of Lyophilization Techniques to rAAV Drug Product Vectors and Baculovirus Viral Banks for Increased Stability and Simplification of Supply Chain

Karpes_LoriLori B. Karpes, PhD, Senior Scientist II, Drug Product Sciences, Voyager Therapeutics

As the gene therapy field matures, greater emphasis on drug product aspects of process development, including the use of advanced techniques, has increased. This work will cover the evaluation of lyophilization for the manufacture of rAAV drug product vectors and Baculovirus viral banks for increased stability and reduced cold chain storage temperatures.

3:30 Close of Conference

* 活動內容有可能不事先告知作更動及調整。