Cambridge Healthtech Institute ’s 2nd Annual

Gene Therapy CMC and Analytics

August 15-16, 2018

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 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 15

7:00 am Registration Open and Morning Coffee (Grand Ballroom Foyer)

Constitution B

8:05 Chairperson’s Remarks

Michael Kelly, PhD, Director, Asset Leadership, Gene Therapy, Biogen

8:15 KEYNOTE PRESENTATION: Development of the First World Health Organisation (WHO) International Standard for Potency and Safety Control of Lentiviral Gene Therapy

Yuan_ZhaoYuan Zhao, PhD, Head of Gene Therapy Section, Division of Advanced Therapies, NIBSC/Medicines and Healthcare Products Regulatory Agency

Changes in production sites and manufacturing processes have become increasingly common, posing challenges to developers regarding reproducibility and comparability of results. Development of a first WHO International Standard for gene therapy, is especially important given the usually orphan nature of the diseases to be treated, hampering the comparison of cross-trial and cross-manufacturing results for the important lentiviral vector platform.

9:00 FEATURED PRESENTATION: Viral Vector Manufacturing and Control: Regulatory Considerations and Challenges

Matthias_RennerMatthias Renner, PhD, Scientist, Federal Institute for Vaccines and Biomedicines, Paul Ehrlich Institute

9:30 Impact of FDA's New Guidances on the Gene Therapy Industry?

Burger_ScottScott R. Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC

10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

Constitution B

10:45 Analytical Testing of Plasmids for Triple Transfection AAV Production: The Challenge of Defining Critical Material Attributes

Lawrence_ThompsonLawrence Thompson, PhD, Principal Scientist, Analytical Research & Development, BioTherapeutics Pharm Sciences, Pfizer

The link between plasmid quality attributes and AAV production is a gap in our current knowledge set. Specifications for plasmids are set based on historical information. As in “it has always worked when we set these criteria”. In this study, we seek to create a link between the plasmid quality as assessed by the current control strategy and the quantity/quality of AAV produced.

11:15 Characterization of a Dimeric Transgene Isoform and Its Potential Impact on AAV Product Quality

Raim_RomanRoman Raim, PhD, Analytical Product Owner, Process Development and Technical Services, Shire

The undesirable outcome of Factor IX (FIX) gene therapy Phase I/II clinical trial with BAX 335 led to a development of second generation of FIX construct. The second generation was developed as a single stranded FIX vector with the same capsid, (AAV8). We investigated the vector sub-population with encapsidated dimeric DNA isoform, checking for its biological activity and evaluating if the degree of this sub-population can be successfully reduced in the final product in order to increase overall product homogeneity.

11:45 Analysis of Purity and Packaging of Gene Therapy Vectors and VLPs to Support Process Development Decisions

Josefina_NilssonJosefina Nilsson, Head, EM Services, Electron Microscopy Services, Vironova

Learn how innovative transmission electron microscopy (TEM)-based technology in combination with image analysis allows automatic imaging as well as automatic viral particle quantification and classification. Case study demonstrating how this technology can be used to automatically quantify the portion of intact as well as disrupted, empty AAV particles. Case study demonstrating how automated TEM-based imaging analysis can examine the composition of different preparation of influenza VLPs to reveal the presence of undesired contaminants.

12:15 pm Enjoy Lunch on Your Own

1:00 Session Break

Constitution B

1:45 Chairperson’s Remarks

Christine Le Bec, PhD., Head of CMC Analytical, Technology Development, Genethon

1:50 Comparison of in vitro and in vivo Potency Assays to Support Phase I Clinical Trials

Christine Hinkle, PhD, Lab Head, Analytics, Gene Therapy Program, University of Pennsylvania

Reliable and functional potency assays are key to supporting successful drug product release, stability, and comparability studies. While in vivo potency assays support drug efficacy, many models are difficult to breed. Functional in vitro potency assays offer the benefit of shorter assay length, decrease dependency on colonies, and demonstrate drug potency and transgene function. An example will be discussed regarding two potency assays developed to support clinical trials.

2:20 Development and Qualification of qPCR and dPCR Vector Genome Titering Methods in an Effort to Evolve Gene Therapy Analytical Paradigms

Jarrod_DeanJarrod Dean, Scientist, Analytical Development, Biopharmaceutics Development, Sanofi

Health authorities emphasize the importance of employing suitable dose-determining methods for gene therapy products. We will discuss the qualification of qPCR and dPCR vector genome concentration platforms in support of gene therapy projects. This presentation spans method development through qualification, highlighting the suitability of dPCR as a platform for titering gene therapy products, and illustrating the benefits of comparing platforms early in product development.

2:50 Analytical Methods for Characterizing Viral Vectors

Russell_GoetzeRussell Goetze, PhD, Scientist, Vector Analytics, bluebird bio

3:20 Multiplex RT-QPCR-Based Expression Assay for RAAV-Delivered Gene Therapy

Dong_XuDong Xu, PhD, Senior Scientist, Analytical Development, Biogen, Inc.

A multiplex reverse transcription quantitative PCR assay was developed to evaluate the expression of a therapeutic transgene delivered by recombinant AAV. It uses a housekeeping gene in human host cells as internal control. The final readout of the assay has been shown to reflect the viral dose at the infection step in a DNA-independent manner.

3:50 Refreshment Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

4:45 Plenary Keynote Session (Constitution Ballroom)

The Next 10 Years: Looking Ahead to Next-Gen Bioprocessing

4:45 pm Chairperson’s Remarks

John Sterling, Editor in Chief, Genetic Engineering & Biotechnology News (GEN)


Murray_Jerry4:50 Digital Transformation to Advance Next-Generation Biomanufacturing through Data Integration and Analytics

Jerry Murry, PhD, Senior Vice President, Process Development, Amgen

Hundreds of millions of data points are currently generated through the development and execution of biopharmaceutical processes. It is expected that the volume and complexity of biomanufacturing data is set to grow exponentially as developers and manufacturers integrate novel sensors, smart materials, process analytical technologies and process automation into laboratories and manufacturing plants. This presentation will describe the value associated with a comprehensive digital strategy incorporating a structured data integration and analytics platform inclusive of AI, predictive modeling and visualization, and how digital transformation can advance next-generation biomanufacturing.

5:20 Driving Change in Biomanufacturing through Innovation in Processes, Technologies and Operations

Eliana Clark, PhD, Vice President, International Manufacturing Operations, Biogen

A critical step in meeting the demand of biologic production worldwide involves implementing disruptive manufacturing technologies, processes and capabilities. This talk will use Biogen’s new manufacturing site in Switzerland, due to go online in 2019, as an example to demonstrate the new processes, operational models and technologies being adopted to drive value through innovation and deliver new medicines in areas such as Alzheimer’s.

5:50 End-to-End Solutions Considering New Trends in Biomanufacturing

Guillaume Plane, MSc, MBA, Manager, Global Development, Biodevelopment Solutions, MilliporeSigma

The presentation will get into the current state of biomanufacturing, from DNA to market approval, considering the way a key supplier can support drug makers to the fullest, thanks to a deep understanding of the trends that could affect our industry in the midterm, including growth of the pipelines, strengthening of regulations, and acceleration of timelines, for development as well as for the set-up of capabilities. Some thoughts and ideas will be proposed to consider commercial manufacturing with single-use equipment.

6:25 Close of Plenary Keynote Session

6:25 10th Anniversary Champagne Celebration in the Exhibit Hall with Poster Viewing (Grand Ballroom)

7:30 End of Day

Thursday, August 16

8:00 am Registration Open and Morning Coffee (Grand Ballroom Foyer)

Constitution B

8:25 Chairperson’s Remarks

Xiaohui Lu, PhD, Director, AAV, Production, CRISPR Therapeutics

8:30 Analytical Strategies on Quantification of AAV Empty Capsids to Support Process Development

Argento_ChrisChristopher Argento, Engineer, Purification Development, Gene Therapy, Biogen

One of the major challenges throughout the process development is to well-characterize empty capsids and remove them effectively. In this presentation, varieties of analytical methods are applied on the same set of samples and compared with their specifications. In our finding, anionic exchange (AEX)-HPLC demonstrates very good correlation with transmission electron microscopy (TEM), and the results of AEX-HPLC are also close to analytical ultracentrifugation (AUC). Finally, strengths and weakness of different methods are summarized and discussed in this presentation.

9:00 Analytical Approaches to Characterize AAV Gene Therapy Products: Host Cell DNA and Host Cell Protein Quantification

Christine_LeBecChristine Le Bec, Head of CMC Analytical, Technology Development, Genethon

In recent years, AAV vectors have been increasingly evaluated in various gene therapy clinical trials. To sustain this, reliable, fast, robust, GMP compliant analytical methods and characterization protocols are needed. Specific analytical assays were performed to assess vector productivity, vector purity, potency and safety. I will present different methods to quantify Host Cell DNA and Host Cell Protein to support the process development and characterize preclinical and clinical lots.

ACF Bioservices 9:30 Steps to Validate an in vitro Relative Potency Assay for Gene Therapy Products 

Doucette_KarenKaren Doucette, MBA, Director, Operations, ACF Bioservices

Owen_AlbertAlbert J. Owen, PhD, Vice President, Scientific Affairs, ACF Bioservices

A validated potency assay is required for approval and lot release of all gene therapy products. The assay must represent the product’s MOA and measure performance relative to a reference standard in a reproducible, controlled manner. This presentation explores advancing an in vitro relative potency assay from development through validation.

 10:00 Coffee Break in the Exhibit Hall with 2nd Session Poster Winner Announced (Grand Ballroom)

Constitution B

10:45 Leveraging ddPCR-Based Assays for AAV Genome Quantitation, Identity, and Integrity

Peter_ClarnerPete Clarner, PhD., Senior Associate Scientist, Analytical Development, Biogen

ddPCR has become a powerful tool for measuring viral vector genome titer and is rapidly replacing qPCR as the assay of choice. We have developed a platform ddPCR method for titering viral vector samples, that also has utility beyond just quantitation. Our assay also provides a genome identity assessment by primarily targeting the gene-of-interest, with additional PCR targets within the vector genome for quality and integrity assessments as well.

11:15 Development of Quantitation Assays for Gene Therapy

Hema Rao, PhD, Scientist, Sanofi Gene Therapy Skill Center

11:45 Quality Control of Gene Therapies

Malliaros_DavidDavid Malliaros, PhD, Senior Director, Quality Control, Ultragenyx

12:15 pm Enjoy Lunch on Your Own

1:15 10th Anniversary Cake Break in the Exhibit Hall with Last Chance for Poster Viewing

1:55 End of Conference


Premier Sponsors:


Millipore Sigma

Unchained Labs