Cambridge Healthtech Institute’s 2nd Annual
Gene Therapy Bioproduction
Developing Scalable, Cost-Effective Gene Therapy Manufacturing Processes
Part of CHI's Ninth Annual The Bioprocessing Summit
August 24-25, 2017 | Westin Copley Place | Boston, MA
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 Bioproduction 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.
Final Agenda
Thursday, August 24
11:30 am Registration Open
12:15 pm Enjoy Lunch on Your Own
1:15 Dessert Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing
1:55 Chairperson’s Remarks
Lance Weed, Ph.D., Vice President, Operations, uniQure
2:00 KEYNOTE PRESENTATION:
Managing Challenges in Late Phase Process Development for Cell and Gene Therapies
Michele Myers, Ph.D., Senior Director, Validation and Lifecycle Management, Cell and Gene Therapy, Platform
Technology & Sciences, GlaxoSmithKline
To date, GSK has optioned three programs as part of its strategic collaboration agreement with the Telethon Institute for Gene Therapy to develop autologous ex vivo gene therapies for the treatment of rare diseases.
This talk will describe the challenges associated with development and implementation of late-stage/post-approval process changes and technology transfer of these programs. The approach to comparability and process qualification will be discussed.
2:45 Lentivirus Development and Scale-Up
Jesse Milling, Scientist II, bluebirdbio
Lentiviral vectors are an ideal platform for indications requiring long-term, stable expression, but the production processes have historically been limited by scale. This presentation will focus on the evaluation of platforms for the next-generation
manufacturing process, with the guiding principles of preserving the comparability of the lentiviral product profile.
3:15 Strategies to Deliver Scalable and Reliable Lentiviral Vector Biomanufacturing
Jeffrey Bartlett, Ph.D., 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 High Resolution Monolithic Columns - Enabling Tool for Understanding Viral Structures and Their Purity
Ales Strancar, CEO, BIA Separations
Monolithic resins with open channels and no diffusive pores enabled the HPLC to be extensively applied for viral structures separations. HPLC columns based on CIM monolithic chromatographic supports are not only able to determine the ratio of
full/empty viral capsids but can further separate and analyse subpopulations of the capsids.
4:00 Refreshment Break
4:15 Retroviral Vector Process Development for CAR T Applications
Paulo Fernandes, Senior Scientist, Process Development, Autolus
While retroviral vectors are one of the preferred choices for stable gene expression, the manufacture of these vectors is still limited in titer and quality. This presentation will focus on the process development efforts at Autolus to manufacture
retroviral batches in sufficient amounts and with the right quality attributes for T-cell transduction and engineering.
4:45 FEATURED PRESENTATION: Development and Production Challenges for CRISPR Gene-Edited Products
Kenneth LeClair, Ph.D., Vice President, Technical Development and Manufacturing, Editas Medicine
This presentation will provide a high-level overview of the considerations involved in the development of CRISPR/Cas9-based gene therapy products. The product development life cycle will be reviewed, starting from product candidate selection,
developability assessments, and final product manufacturing. Examples of direct-inject viral vector therapies and of ex vivo engineered cell products will be presented.
5:15 Close of Day
6:00 – 9:00 Recommended
Dinner Short Course*
SC9: Transient Protein Production in Mammalian Cells
* Separate registration required
Friday, August 25
8:00 am Registration Open and Morning Coffee
8:25 Chairperson’s Remarks
Johannes C.M. van der Loo, Ph.D., Director, Clinical Vector Core, The Raymond G. Perelman Center for Molecular and Cellular Therapies, Children’s Hospital of Philadelphia
8:30 KEYNOTE PRESENTATION:
Considerations and Challenges When Establishing a New Manufacturing Facility
Lance Weed, Ph.D., Vice President, Operations, uniQure
Over the past four years, uniQure has invested more than $25 million in designing, constructing and equipping its 55,000-square foot facility with state-of-the-art laboratories and commercial-scale production capabilities. This presentation
will discuss the challenges in establishing a new manufacturing facility from scratch, and what small companies should consider when deciding whether to build their own manufacturing capability or use contract manufacturing.
9:00 Manufacturing Considerations for AAV Gene Therapies
K. Reed Clark, Ph.D., Senior Vice President, Pharmaceutical Development, Dimension Therapeutics
This presentation will discuss our approaches for scalable manufacturing to inform late-stage manufacturing of AAV-based gene therapy products. Lessons learned in the development of mammalian-based production platforms will be highlighted
and the necessary analytics to support efficient process development discussed.
9:30 Separation of Virus, VLP and Extracellular Particles
Alois Jungbauer, Ph.D., Professor, Institute of Biotechnology, University
of Natural Resources and Life Sciences (BOKU)
Downstream processing of enveloped bio-nanoparticles is very challenging due to biophysical and structural similarity between correctly assembled particles such as VLP, viruses, exosomes and contaminating vesicular particles are present
in the feedstock. Direct capture by connective media or flow through chromatography are used in connection with linear gradient elution to separate the products from other vesicles. Also advanced analytics will be addressed to discriminate
the different particles.
10:00 Networking Coffee Break
10:30 Formulation Development for AAV Gene Therapy Application
Tanvir Tabish, Head, Drug Product Development for Gene Therapy, Device and Combination
Products, Shire
A set of formulations was screened. One was found to stabilize the AAV based product for at least 5 months when stored frozen, and for at least 4 months when stored at +5°C. No visible particles together with no significant loss of
infectivity or total particle titre was observed. SDS-PAGE and SEC did not show significant chemical or physical degradation. Adsorption studies did not reveal any loss with contact materials.
11:00 Advantages and Challenges of Early Phase Clinical Manufacturing in an Academic Setting
Johannes C.M. van der Loo, Ph.D., 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 has manufactured pre-clinical- and clinical-grade AAV and lentivirus-based custom viral vector products in support of early phase clinical studies. Manufacturing
in an academic non-profit setting, which provides significant advantages to new investigators, includes unique challenges that require consideration. Awareness of these challenges helps both manufacturers and investigators streamline
the process of bringing new gene therapy products to the clinic.
11:30 Working with Gene Therapy CMOs
Jerrod Denham, Ph.D., Principal & Senior Consultant, Dark Horse Consulting
12:00 pm Sponsored Presentation (Opportunity Available)
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Session Break
1:25 Chairperson’s Remarks
Norman Goldschmidt, President, Genesis
1:30 Development and Optimization of a Serotype-Independent Method of Adeno-Associated Virus Harvest and Purification
Bryan Piras, Ph.D., Senior Scientist II, Process Development, Therapeutics Production and
Quality, St. Jude Children’s Research Hospital
We assessed commercially available scalable single-use chromatography membranes for their ability to capture AAV vectors directly from cell culture media and lysate. We developed a simple technique that integrates release of cell-associated
AAV particles followed by capture and recovery on a hydrophobic interaction chromatography membrane. This process is serotype-independent and provided efficient capture and recovery of AAV1, AAV3-like, AAV5, and AAV8 particles from
cell culture media and cell lysate.
2:00 AAV Vectors: From Discovery to Large-Scale Clinical Manufacturing: An Academic Success Story
Nathalie Clément, Ph.D., Associate Director and Associate Professor,
Powell Gene Therapy Center, Pediatrics, University of Florida
A brief history of AAV vectors at the University of Florida from their first engineering to the first clinical trials will be presented. Current manufacturing protocols developed at the Powell gene therapy will be discussed and compared,
with a strong emphasis on the recently implemented large-scale production platform in suspension cells using HSV-system. Data will cover yields, quality, potency, purity and other CMC requirements for GMP manufacturing.
2:30 Engagement with FDA and Facility Design for Cell and Gene Therapies
Norman Goldschmidt, President, Genesis
Johannes C.M. van der Loo, Ph.D., Director, Clinical Vector Core, The Raymond G. Perelman Center for Molecular and Cellular Therapies, Children’s Hospital of Philadelphia
As cell and gene therapies are moving forward to becoming mainstream treatment modalities, the relationship of hospitals and universities with the FDA is rapidly evolving. Organizations producing phase 2 and later clinical therapies are
receiving more attention and scrutiny from regulators. This session will look at the general principals of approvable cGMP facility design and one organization’s approach to proactively engaging with FDA during the design process
to manage risk and allow incorporation of FDA’s latest thinking in facility design at an early stage.
3:00 Gene Therapy to Combat Chemical Weapons
Venkaiah Betapudi, P.hD., Research Investigator, US Army Medical Research Institute of Chemical Defense
3:30 End of Conference