Cambridge Healthtech Institute’s 3rd Annual

Gene Therapy Analytics & Manufacturing

CMC Strategies, Tools, Process Development, and Scale-Up Considerations for Gene Therapies

January 18 - 19, 2022 ALL TIMES PST

The rapid boom in gene therapy medicines must be met with the fast development of robust, scalable, and well-characterized processes and products. Cambridge Healthtech Institute’s 3rd Annual Gene Therapy Analytics & Manufacturing conference will bring together leading scientists from the biopharmaceutical industry, academia, and government to discuss unpublished, in-depth case studies, new technologies, assay on CMC strategies, characterization, critical quality attributes, analytical toolbox, process development and scale-up, and the role of CDMOs in manufacturing of gene-based therapies. This conference is preceded by a sister conference, the 3rd Annual Cell Therapy Analytics & Manufacturing.

Session Room: Sapphire D

Tuesday, January 18

1:00 pm Registration (Sapphire West Foyer)
1:30 pm Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
2:00 pm Organizer's Welcome Remarks

Nandini Kashyap, MPharm, Conference Director, Cambridge Healthtech Institute

2:05 pm

Chairperson's Opening Remarks

Dominic Clarke, PhD, ISCT Process & Product Committee Co-Chair & CTO, Cell and Gene Therapy, Discovery Life Sciences

Nucleic Acids as Household Medicine: Living in the World of RNA Therapeutics  

Mano Manoharan, PhD, Distinguished Scientist & Senior Vice President, Innovation Chemistry, Alnylam Pharmaceuticals

Synthetic small interfering RNAs (siRNAs) are potent inhibitors of gene expression; these agents act through the natural RNA interference (RNAi) pathway. Our laboratory demonstrated the very first in vivo RNAi mediated silencing in mouse liver and jejunum in 2004.To deliver therapeutic siRNAs into liver hepatocytes, we have further developed a three-pronged approach with the goals of enabling delivery to hepatocytes after both intravenous and subcutaneous administration. These methods include chemical modification of siRNAs, lipid nanoparticle (LNP) formulation of siRNAs, and multivalent N-acetylgalactosamine (GalNAc) conjugation of siRNAs and how GalNAc platform is used for the delivery of siRNAs for several approved drugs and a rich pipeline.

Jane Luo, PhD, Senior Scientist, BioPharma Application Development, SCIEX

Recombinant adeno-associated viral vectors are an important technology for novel in vivo gene therapeutics. This presentation will highlight a high throughput, QC-ready, platform approach to AAV characterization.

  • Discover analytical workflows for product and process related impurities including viral capsid purity, genome integrity and empty/full vector ratio assessment.
  • Understand how these methods can be adopted in both high throughput and quality control settings
3:40 pm Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)


4:30 pm

Characterization of Primary and Higher-Order Structures for AAV Vectors

Susumu Uchiyama, PhD, Professor, Biotechnology, Osaka University

Detailed and comprehensive analysis of virus vectors are required to ensure their efficacy and safety. Recently, novel biophysical characterization methods of AAV have been emerged. Here we introduce primary structure analysis by the combination of information from CE-SDS and LC-MS, which also provides accurate ratio of VPs. Then, multiwavelength SV-AUC will be introduced that enable to identify comprehensive size distribution profile of particles with information on constituents in AAV samples.

5:00 pm

Development of an IEC-UV HPLC Method for Determination of AAV Empty Capsids

Dana Tribby, Associate Scientist III, Analytical Development & Gene Therapy Chemistry, Biogen

Current manufacturing and purification processes of adeno-associated virus gene therapy products result in relatively low product yields. The battery of analytics required for complete in-process testing, product characterization, lot release, and stability testing can consume significant amounts of clinical lots. Empty capsids are a key product-related impurity for which the FDA requires batch release testing. An assay suitable for routine GMP QC testing that can accurately measure %Empty capsids in both in-process samples and DS/DP of Gene Therapy products is needed. This presentation describes a new method of quantifying empty capsids, enabling an end-to-end analytical control strategy.

6:00 pm Close of Day

Wednesday, January 19

7:30 am Registration (Sapphire West Foyer)
8:00 am BuzZ Sessions with Continental Breakfast (Sapphire Foyer)

PepTalk BuzZ Sessions are focused, stimulating discussions in which delegates discuss important and interesting topics related to upstream protein expression and production through downstream scale-up and manufacturing. This is a moderated discussion with brainstorming and interactive problem-solving between scientists from diverse areas who share a common interest in the discussion topic. Continue to check the event website for detailed discussion topics and moderators.

BuzZ Table 4: Stability Differences of AAV Serotypes

Jared S. Bee, PhD, Director, Formulation & Drug Product Development, REGENXBIO, Inc.
  • Do they have different aggregation propensities?  
  • Is a single formulation suitable for different serotypes?  
  • Do serotypes have different freeze/thaw stability?​​

BuzZ Table 5: Cryopreservation Challenges of Biologics, Gene Therapy, and Cell Therapy Modalities

Sanket Patke, PhD, Associate Director, Sanofi


Session Room: Sapphire D

9:00 am

Chairperson's Remarks

Santoshkumar L. Khatwani, PhD, Director, Analytical Development, Sangamo Therapeutics
9:05 am

Characterization of Product and Process-Related AAV Impurities Using LC-MS

Jonathan Bones, PhD, Principal Investigator, Characterisation and Comparability Laboratory, National Institute for Bioprocessing Research and Training (NIBRT), Ireland

Regulatory guidelines require the determination of product and process-related impurities for gene therapy products. Here, we present methods for the characterization of AAV capsids on various levels using liquid chromatography-mass spectrometry. Application of native mass spectrometry for rapid assessment of empty and full capsids will also be presented. We will also outline methods for the analysis of residual host cell proteins at various stages of AAV downstream purification.

9:35 am

Multi-Attribute Assessment of AAV Samples by Size Exclusion Chromatography

Dennis Delgado, Principal Research Associate, Analytical Development, Sanofi-Genzyme

In this presentation, we will discuss the development of a high-throughput, QC-friendly multi-attribute assessment of AAV products and process-intermediates by size exclusion chromatography.

Kevin Lance, PhD, Director of Analytics Marketing, Unchained Labs

Gathering the info you need about your AAVs chews up too much sample and time. From just microliters of AAV, Stunner gets you answers on titer, empty/full ratio and aggregation. Uncle gives a unique look at the stability of your capsids to solve capsid engineering and formulation problems. We'll look at how to gather so much info from so little sample, and how it can make your analytical strategy more robust.

10:35 am Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
Santoshkumar L. Khatwani, PhD, Director, Analytical Development, Sangamo Therapeutics


An overview of analytical development for AAV product characterization:

  • AAV product characterization challenges
  • Empty/Full capsids quantitation
  • Viral protein ration quantitation
Gabriella Kiss, PhD, Director of Sales, North America, Sales, Refeyn

Mass photometry is a novel, easy-to-use bioanalytical technology that measures the empty-full AAV capsid ratio in minutes using minimal sample amounts and without the need of sample preparation. Circumventing the requirement of large capital expense and skilled operators, it can be employed throughout the manufacturing process. We present a novel mass photometry instrument dedicated to the challenges of AAV characterization. 


12:45 pm Session Break
Tim Geiger, Senior Manager, Field Application Scientists, Western Business Unit, Bio-Techne

Innovative analytical tools from Bio-Techne can support gene therapy workflows from discovery to quality control and address certain critical quality attributes of your therapeutic. Today’s presentation will explore the many ways viral vector analysis is streamlined with ProteinSimple instruments and how our products improve line-of-sight across the development process. 

1:25 pm Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing (Sapphire Ballroom)


2:15 pm

Chairperson's Remarks

Luca Biasco, PhD, Director, R&D, AVROBIO, Inc.
2:20 pm

Stability of Adeno-Associated Virus Serotype 8 and 9 Gene Therapy Vector Formulations

Jared S. Bee, PhD, Director, Formulation & Drug Product Development, REGENXBIO, Inc.

There has been a rapid increase in the number of clinical studies of gene therapy using adeno-associated virus (AAV) vectors. There are several different AAV serotypes which have differences in their chemical and physical stability. In this presentation, we share data on the stability of AAV8 and AAV9 in different formulations under conditions relevant to manufacturing, labeling, long-term storage, and clinical use.


2:50 pm

High-Resolution Single-Cell Profiling of Human Hematopoietic Stem Cell Drug Products

Luca Biasco, PhD, Director, R&D, AVROBIO, Inc.

Human CD34+ cells are the core components of ex vivo lentiviral gene therapy (GT) for the systemic treatment of monogenic diseases. Understanding the changes occurring in hematopoietic stem and progenitor cells (HSPC) upon genetic engineering is critical in determining the potency of GT drug products. We combined state-of-the-art multiparameter flow cytometry and next-generation single-cell technologies for the comprehensive characterization of the main sources of human HSPC and of different engineering conditions.

3:20 pm

Optimizing Viral Vector Process Development

Stephen Soltys, PhD, Vice President, Process Development, Kriya Therapeutics

Our cGMP production suites and single-use systems will allow the production of multiple products simultaneously at up to 3,000-liter bioreactor scale. We are developing reliable and robust production systems that can deliver higher amounts of AAV product per batch.

3:50 pm

Current Challenges in Gene Therapy Technical Development

Mark Galbraith, PhD, Former Head, Quality Control and Analytical Sciences, Spark Therapeutics

Implementation of a manufacturing process that assures a predefined quality of the product is a critical requirement for the licensing and marketing of every CGT product. This presentation will discuss the current challenges in gene therapy technical development to ensure safe, well-characterized products.

4:20 pm Close of Conference