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

Managing Challenges in Late Phase Process Development for Cell and Gene Therapies

Michele_MyersMichele 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_MillingJesse 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

Jeff_BartlettJeffrey 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.

 BIA separations3:45 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_FernandesPaulo 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

Ken_LeClairKenneth 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

6:009:00 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

Considerations and Challenges When Establishing a New Manufacturing Facility

Lance_WeedLance 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

Reed_ClarkK. 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 rAAV Vector Production in the Baculovirus/Sf9 Platform and in HEK293 Suspension Cell System

David_DismukeDavid Dismuke, Director, Vector Production, Voyager Therapeutics

Gene therapy vectors based on recombinant adeno-associated virus (rAAV) have continued to demonstrate their utility as effective, dependable, and safe tools for gene delivery. They have been used extensively in clinical trials to replace or silence genes in a variety of tissues, including the eye, brain, muscle, and the liver. As the success of AAV gene therapy has grown, so have the doses and demand for the vectors. To supply the high titers required for late-stage clinical trials and expected commercial demands, several manufacturing platforms have been developed, including the baculovirus/Sf9 platform and transient transfection in HEK293 suspension cells. While both of these systems are capable of generating high quality AAV vectors, the baculovirus/Sf9 system offers higher yields and fully scalable unit operations.

10:00 Networking Coffee Break

10:30 Scalable and Cost-Effective Production of Diverse Recombinant AAVs

Mark_FoxMark Fox, Ph.D., Director, Process Sciences, 4D Molecular Therapeutics

rAAVs have become a well-accepted gene therapy delivery detail, with an increasing diversity of serotypes and variants entering clinical testing. But many AAV manufacturing processes still use labor-intensive, expensive, non-scalable and cGMP compliance-resistant unit operations. 4D has adopted a strategic approach to process development for its portfolio of AAV products. We will discuss this cost-effective, scalable and compliant manufacturing platform and its potential breadth of application.

11:00 Advantages and Challenges of Early Phase Clinical Manufacturing in an Academic Setting

Jan_VanderLooJohannes 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 Separation of Virus, VLP and Extracellular Particles

Alois_JungbauerAlois 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.

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_PirasBryan 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_ClementNathalie 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 Formulation Development for AAV Gene Therapy Application

Tanvir_TabishTanvir 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.

3:00 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.

3:30 End of Conference

OutlookYouTubeFacebookLinkedInTwitter #BPSMT