Cambridge Healthtech Institute’s Inaugural
Gene Therapy CMC and Analytics
Part of CHI's Ninth Annual The Bioprocessing Summit
August 23-24, 2017 | Westin Copley Place | Boston, MA

Gene therapy is an extremely promising technique for the treatment of incurable diseases such as cancer and genetic disorders such as hemophilia. However, the analysis, characterization and delivery of these unique products remain an issue.

Cambridge Healthtech Institute’s Gene Therapy CMC, Quality and Analytics meeting uncovers the practical challenges facing vector-based gene therapy analytics, assay development, quality control, vector development and delivery.

Final Agenda

Wednesday, August 23

7:00 am Registration Open and Morning Coffee


8:05 Chairperson’s Opening Remarks

John Pieracci, PhD, Director, Purification, Biogen

Analytical Testing Program for GMP Manufacturing Scale of AAV-Based Gene Therapy Vectors

Ernst_BoehmRoman Raim, PhD., Analytical Product Owner, Analytical Development, Shire

Production of AAV8-based gene therapy vectors requires an analytical strategy to enable process monitoring, process control, and release of clinical GMP batches. Implementation of an analytical method platform to assess key quality attributes was a priority. Potency assignment of the final product was most accurate when based on total capsid particle concentration, supported by vector genome concentration, degree of genome containing particles, and proof of efficacy in an in vivo model.


9:00 Global cGMP Strategy, Building a Global CMC Strategy

Ohad_KarnieliOhad Karnieli, Ph.D., MBA, CEO and Co-Founder, Atvio Biotech Ltd; Chair, Process and Product Development Subcommittee, International Society of Cellular Therapies (ISCT)

As therapies get closer to clinic, there is a growing need for global expansion. This global expansion not only results in the need for manufacturing scaling, but opens new challenges of meeting the different regulatory demands and supply limitations. Such challenges have to be considered early on in the products’ lives and have to be planned carefully by building a global CMC strategy. The talk will discuss the challenges and provide case studies and examples for CMC strategies.

9:30 CMC Focus during Innovation of Vector-Based Gene-Therapy Products

Arie_vanoorschotArie van Oorschot, Ph.D., Senior Consultant, CMC, Xendo B.V.

The application of gene-therapy products is diverse and developing rapidly. A few gene-therapy products are on the market, confirming that application of gene-therapy is feasible. Despite these successes, the general industrial experience and requirements can be considered limited. Typically, gene-therapy products are complex biologics and many iterations and a problem-solving attitude is required throughout development. To support the activities of multiple disciplines in parallel, an integrated CMC focus is essential.

Rockland 10:00 Coffee Break in the Exhibit Hall with Poster Viewing


10:45 Analytical Development and Testing Strategies for Viral Vectors Transitioning from Research to Non-Clinical and Clinical Stages

Eric_PastourEric Pastor, Principal Scientist, Biopharmaceutics Development, Sanofi US

It is important to characterize and understand critical quality attributes of viral vector products throughout drug development. Here, we present analytical development strategies and paradigms as viral vectors transition from research to non-clinical and clinical stages. We will discuss lessons learned from past experiences as we move viral vector analytics from conception to validation and present ideas on how to accelerate method development.

11:15 Qualification of AAV Vector Potency

Lyndi_RiceLyndi Rice, Ph.D., Director, Analytics, University of Pennsylvania

The quantification of AAV vector potency over time and compared to other vectors is important for characterization for release and as part of stability programs. Potency assays are useful for determining transgene expression, activity and/or function in vitro or in vivo, and should be qualified for investigational drug product release. An example of potency assay development and qualification will be discussed.

ACF Bioservices 11:45 Using Manufacturing Software to Monitor Complex and Challenging Cell-Based Potency Assays for Gene Therapy Products  

Patrick_DetingerPatrick Dentinger, President, CEO, ACF Bioservices, an Absorption Systems Company

Translational science includes many cell-based assays. Manufacturing is a dynamic process that requires monitoring. Our software tracks every step of a process from removal from the cell bank to manufacture and disposition of assay plates. We use the software for tracking a relative potency assay for an AAV gene vector.

  Fujifilm Diosynth12:00 pm Analysis of Viral Vector Based Therapeutics: A Toolbox Approach  

Cari Sadowski, Ph.D., Associate Principal Scientist, Group Leader, Virology Analytical Development, FUJIFILM Diosynth Biotechnologies

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:00 Session Break

1:45 Chairperson’s Remarks

John Pieracci, PhD, Director, Purification, Biogen

1:50 Qualification/Validation of Assays to Support the Release and Characterization of Recombinant Adeno-Associated Virus Clinical Trial Materials

Michelle Joubert, Ph.D., Scientist, Sanofi

It is important to ensure that gene therapy viral vector assays are suitable for their intended use prior to releasing clinical trial materials. At Sanofi, this is accomplished by tailoring qualification or validation studies to the method types used at different stages of drug development. The strategy and results obtained from qualifying and validating methods for a gene therapy analytical paradigm will be discussed.

2:20 Gene Therapy Potency Assay Development 

Michael_HocquemillerMichael Hocquemiller, Ph.D., Senior Scientific Manager, Lysogene

Mucopolysaccharidosis type IIIA (MPSIIIA) is a lysosomal storage disorder caused by mutations in N-sulfoglucosamine sulfohydrolase (SGSH), resulting in heparan sulfate (HS) accumulation and progressive neurodegeneration. Our approach is intracerebral gene therapy using AAV serotype rh.10 carrying the human SGSH cDNA. This talk will focus on the development of an in vitro potency assay for demonstrating batch-to-batch consistency of a gene therapy product.

2:50 Development and Characterization of Mir-Attenuated Oncolytic Viruses

Mike_PagliaMichael Paglia, Ph.D., Senior Director, CMC Operations, Oncorus

Development of a robust manufacturing process for therapeutic oncolytic herpes virus requires process understanding gained through process characterization. Process development and analytical strategies to ensure successful scale up and manufacturing for mir-attenuated oncolytic herpes virus will be presented.

3:20 Demonstrating Comparability during Gene Therapy Tech Transfer

Scott_BurgerScott Burger, M.D., Consultant, Advanced Cell and Gene Therapy Ltd.

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.

3:50 Refreshment Break in the Exhibit Hall with Poster Viewing


6:00 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 Close of Day

Thursday, August 24

8:00 am Registration Open and Morning Coffee


8:25 Chairperson’s Remarks

Xiaohui Lu, Ph.D., Senior Scientist, Analytical Development, Biogen 


8:30 The Quest for Accurate AAV Capsid Quantification

Xiaohui Lu, Ph.D., Senior Scientist, Analytical Development, Biogen

AAV capsid titers are often determined using commercial ELISA assay kit. However, the reference standard in the commercial kits subject to batch-to-batch variations, and its value assignment can also be improved. In this case study, we evaluated alternative approaches, and generated internal reference standard with orthogonally determined concentration. This customized assay will enable reliable capsid titer quantification over long terms. 

9:00 Analytical issues for AAV gene therapy products: vector genome titer and full/empty viral particles quantification 

Christine Le Bec, PhD, Head of Analytical Development, Genethon

Selected analytical assays were developed to assess the vector productivity, vector purity, biological activity/potency. The quantitative PCR (qPCR) is the current gold method of titrating AAV genomes. The Droplet Digital PCR (ddPCR), a new technology which has been designed for accurate DNA quantification, could improve titer determination. Comparison between these two methods will be discussed. The presentation will also cover methods to determine the ratio of full/empty viral capsids

9:30 Sponsored Presentation (Opportunity Available)  

10:00 Coffee Break in the Exhibit Hall with Poster Viewing


10:45 Insights in Measuring DNA Impurities by Real-Time PCR in Clinical AAV Vectors

Sebastiaan_vanZalenSebastiaan van Zalen, Ph.D., QC Manager, Clinical Vector Core, The Raymond G. Perelman Center for Molecular and Cellular Therapies, Children’s Hospital of Philadelphia

Purified AAV vectors contain measurable levels of process-related DNA impurities. Residual levels of plasmid and host cell DNA in the vector can have direct product safety implications and therefore have to be accurately measured. We compared suitability of currently-available quantitative PCR platforms for measurement of DNA impurities in AAV vectors within clinical titer range and assessed other contributing factors such as titer, vector genome length, serotype, and manufacturing method.

11:15 Identity Assessment of AAV Preparations

Simon_PacouretSimon Pacouret, Research Fellow, Grousbeck Gene Therapy Center, Massachusetts Eye and Ear, Harvard Medical University; INSERM UMR 1089

Viral vector preparations for gene therapy are complex biologics. With the steady progression of the adeno-associated viral vector (AAV) platform, identity assessment of vector preparations is key. Here, we will review the available assays to assess identity on a genomic, protein, and particle level. In addition, we will describe our work on AAV-ID, a time- and cost-effective method to establish lot-to-lot identity information on formulation, protein, and particle identity.

11:45 PANEL DISCUSSION: Ensuring the Quality of Gene Therapies

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 Close of Conference