Cambridge Healthtech Institute ’s 3rd Annual
Gene Therapy Manufacturing
August 16-17, 2018
It is an exciting time for gene therapy – therapies on the market, encouraging clinical data and a long list of pharma collaborations. Pricing and reimbursement takes a majority of the headlines but equally important is producing these therapies
in a scalable, cost-effective and robust way, all the while developing a clear CMC and characterization profile that satisfies the regulators.
Cambridge Healthtech Institute’s Gene Therapy Manufacturing meeting 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.
Thursday, August 16
11:30 am Registration Open (Grand Ballroom Foyer)
12:15 pm Enjoy Lunch on Your Own
1:15 10th Anniversary Cake Break in the Exhibit Hall with Last Chance for Poster Viewing (Grand Ballroom)
1:55 Chairperson’s Remarks
John Pieracci, PhD, Director, Purification, Biogen
2:00 KEYNOTE PRESENTATION: Challenges and Strategies for the Development of a Robust, Scalable, Cost-Effective Biomanufacturing Process
Sadettin Ozturk, PhD, Senior Vice President, Process and Analytical Development, MassBiologics
The use of viral vectors has increased in recent years, both as gene therapies and as vectors for ex vivo cell therapy products. Industrialization of viral vector manufacturing is maturing as companies tackle problems
in process control, scale-up, facility design, characterization and quality, and regulatory considerations. This presentation will examine the current state of the art, emerging technologies and challenges.
2:45 Enabling Industrial Scale Production of Lentiviral Vectors for Gene Therapy
Kelly Kral, PhD, Associate Director, Vector Process Development and Manufacturing, bluebird bio
Lentiviral vectors are an ideal platform for indications requiring long-term, stable expression, but the production processes have historically been limited by scale. As the field has now entered commercialization, there is demand for larger quantities
of vector, driving the need for more scalable processes. This presentation will review the development, scale-up, and tech transfer of our suspension-based lentiviral vector process.
3:15 Strategies to Deliver Scalable and Reliable Lentiviral Vector Biomanufacturing
Jeffrey Bartlett, PhD, CSO, Calimmune, Inc.
Large-scale clinical production of lentiviral vectors (LV) using current good manufacturing practice (cGMP) methods comes with significant challenges. We have established the Cytegrity stable cell line system for LV bioproduction and have defined key
process, quality and regulatory parameters needed to achieve desired productivity and quality across multiples scales and different bioproduction systems. This approach has allowed the production of LV required for Phase I and II clinical trials,
while paving the way for future commercialization.
3:45 Evolving Process-Centric
Mike Sheehan, MSc, MBA, PMP, Senior Project Manager, DPS Group
Increasingly gene therapy products transitioning from clinical phase to commercial manufacture is driving demand for companies to provide additional capacity. Bringing products to market requires exploring opportunities for leading edge facility design,
implementing new & evolving technologies, responding to scalability, speed to market and financial considerations.
4:00 Refreshment Break (Foyer)
4:15 Scalable Lentiviral Vector Production Using HEK293 Suspension Cells
Parminder S Chahal, Research Officer, Human Health Therapeutics Research Centre, National Research Council Canada
We have developed expertise in the production of lentiviral vectors (LV) using packaging cell lines and stable producers. Both grow in suspension and in serum-free conditions. Using a stable producer cell line that produces LV expressing GFP, we have
compared different modes of operation in bench-scale bioreactors (batch, fed-batch and perfusion). Next, a battery of filters and supplements were evaluated for clarification. A maximal recovery of 78% was obtained.
4:45 Development and Characterization of Novel Micro-RNA Attenuated Oncolytic Herpes Simplex Viruses
Jonathan Platt, PhD., Senior Research Scientist, CMC Operations, Oncorus
Oncorus is developing next generation HSV-based oncolytic virus with enhanced potency for tumor cell killing and recruitment of the immune system. Our innovative miR-attenuation strategy enables robust viral replication in tumor cells, while preventing
replication in healthy tissue. The development and characterization of therapeutic oHSV requires thorough product understanding gained through process characterization. Strategies for development and characterization of manufacturing processes centered
around a strong organizational infrastructure will be presented.
5:15 End of Day
FRIDAY, AUGUST 17
8:00 am Registration Open and Morning Coffee (Grand Ballroom Foyer)
8:25 Chairperson’s Remarks
Nathalie Clément, PhD, Associate Director and Associate Professor, Powell Gene Therapy Center, Pediatrics, University of Florida
8:30 FEATURED PRESENTATION: rAAV Vector Design, Capsid Directed Evolution and Scale Up Activities Using the BEVS System
Jacek Lubelski, PhD., VP, Global Pharmaceutical Development, uniQure
9:00 Towards a Pivotal Process for AAV Manufacture with HSV
David Knop, PhD, Executive Director, Process Development, AGTC
9:30 Large-Scale Manufacturing of Clinical Grade AAV in the Academic Setting
Nathalie 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.
10:00 Networking Coffee Break (Foyer)
10:30 Scale-Up Approach to AAV Manufacturing
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
The Clinical Vector Core at the Children’s Hospital of Philadelphia manufactures preclinical- and clinical-grade AAV for academia and industry-sponsored clinical trials. With the field of gene therapy maturing, there is a growing need for larger
scale products. We will discuss a strategy for scale-up that builds on our existing mammalian adherent cell-based manufacturing platform.
11:00 Virus-Like Particles and Other Extracellular Particles from Insect and Mammalian Cells
Alois Jungbauer, PhD, Professor, Institute of Biotechnology, University of Natural Resources and Life Sciences
Virus-like particles and other extra cellular particles are a next generation of biopharmaceuticals. They can be produced by a wide variety of host cells. The challenge is the production of high titers and downstream processing. The particle of interest
are contaminated with other particles with similar biophysical properties and therefore difficult to separate. Examples will be given for 3 different cell types.
11:30 Considerations for the Purification Process Characterization of an AAV from Recovery to Drug Substance
Ratish Krishnan, PhD, Scientist, Bioprocessing Research & Development, Pfizer
Smart and efficient approaches for lab-scale characterization are required to ensure a robust adeno-associated manufacturing process. Specific challenges related to the uniqueness of characterizing an AAV manufacturing process will be discussed. Focus
will be given to working with limited quantities of material and employing assays that are still being defined.
12:00 pm Next Generation AAV Viral Vector Manufacturing: Proven Technologies with a Modern Twist
Sandhya Buchanan, Director, Upstream Process Development, FUJIFILM Diosynth Biotechnologies
Current approaches to commercial-scale manufacture of viral vectors have been successful for many early phase trials and some late phase trials. Unique challenges/limitations arising for AAV manufacturing include quantities sufficient for patient needs
and consumables for manufacturing. We discuss proven technologies blended with modern advancements to meet the needs of the advancing field of gene therapy.
12:30 Enjoy Lunch on Your Own
1:25 Chairperson’s Remarks
Chia Chu, Senior Principal Scientist, Bioprocess Research & Development, Pfizer
1:30 FEATURED PRESENTATION: Separation of Full and Empty AAV Particles Using Scalable Isocratic Elution Chromatography
Meisam Bakhshayeshi, PhD, Head, Purification Development, Gene Therapy, Biogen
Robust and efficient removal of AAV empty particles is a critical part of the AAV manufacturing process. In this study, we present a scalable ion exchange chromatography process with isocratic wash and elution to separate full and empty particles. A combination
of mono- and di-valent salts were used as eluents to achieve the high degree of resolution required for this separation. High product purity and recovery was achieved from this process.
2:00 Lyophilisation of AAV Gene Therapy Product
Tanvir Tabish, PhD, Head, Drug Product Development for Gene Therapy, Device and Combination Products, Shire
The gene therapy adeno-associated virus (AAV) subtype 8 containing Factor IX (FIX)(BAX335) was formulated in a new proprietary buffer and lyophilized. A stability study was established with the lyophilized material to determine its stability profile at
the accelerated temperature of +5°C over a 10 month period. The freeze-dried product displayed an improved stability profile when stored at a temperature of +5°C. We demonstrated the feasibility of lyophilisation of the AAV viral drug product
in the formulation buffer.
2:30 AAV Manufacturing at 2,000L Scale
Alex Fotopoulos, PhD., Senior Vice President, Technical Operations, Ultragenyx.
Changing the manufacturing site (tech transfer) should always include an assessment of comparability, however the ability to demonstrate this varies between early and late development. This talk will discuss common pitfalls and mistakes and highlight
key aspects of the comparability exercise.
3:00 CMO Selection for Cell & Gene Therapy
Chad Green, PhD, Principal & Senior Consultant, Dark Horse
As the diversity of CMOs available for cell and gene therapies continues to grow worldwide, identifying the most suitable to engage is becoming an increasingly complex challenge. This presentation will address fundamental questions, such as whether
a CMO is even the best choice for manufacturing before progressing to provide concrete guidance on the critical questions to ask prospective CMOs (and yourself), how to ask them and how to analyze the answers and make an optimal, rational choice.
3:30 Close of Conference