ARM Events

The Alliance for Regenerative Medicine and US Pharmacopeia held a 1.5 day workshop on AAV Analytical Characterization on March 8-9, 2023, in the Washington DC area. This workshop covered various topics on AAV quality, including full / empty capsid characterization, potency assay, and titer measurements.

About This Workshop

Adeno-associated virus (AAV)-based gene therapies have shown promise for the treatment of many diseases, including rare diseases with unmet medical needs. Despite their extensive clinical application and licensure as marketed products, further efforts are required to increase product understanding with regard to their characteristics that may have an impact on clinical efficacy, safety, or immunogenicity. This workshop will cover various topics on AAV analytical characterization, including full / empty capsid characterization, potency assay, and titer measurements. This workshop aims to review state-of-the-art methodologies, share learnings on approaches for different products, with the ultimate goal of moving towards harmonized methods and agreements on potency expectations.

Agenda

Wednesday, March 8

7:30 – 8:30am: Registration and Breakfast

8:30 – 8:50am: Opening Remarks

Josephine Lembong, Ph.D., Manager, Scientific and Industry Affairs, Alliance for Regenerative Medicine (ARM)
Diane McCarthy, Senior Director, Biologics, US Pharmacopeia (USP)

8:50 – 9:30am: How GC Titer, Full-Empty Profile and Potency Correlate and What We Know about Clinical Relevance

Khandan Baradaran, Ph.D., Vice President, Regulatory CMC, Ultragenyx Pharmaceutical

9:30 – 10:00am: USP Roadmap for AAV: Current Activities, Collaboration, and Future Directions

Jerome Jacques, Principal Scientist, USP

10:00 – 10:30am: Removal of Empty AAV Capsids to Undetectable Levels Using Orthogonal Purification Steps – Product Quality and Process Robustness Considerations

Rahul Sheth, Ph.D., Senior Scientist 2, Purification Process Development, BioMarin Pharmaceutical

10:30 – 11:00am: Characterization of Defective – Interfering Particles through Next Generation Sequencing

Lauriel Earley, Ph.D., Senior Scientist, Shape Therapeutics

11:00 – 11:15am: Morning Break

11:15 – 11:45am: Evaluating PTMs in Relation to AAV Capsid Integrity

Adriana Kita, Ph.D., Associate Director, Analytical Development, Ultragenyx Pharmaceutical

11:45am – 12:30pm: Panel Session

Khandan Baradaran, Ph.D., Vice President, Regulatory CMC, Ultragenyx Pharmaceutical (Moderator)
Andrew Byrnes, Ph.D., Chief, Gene Transfer and Immunogenicity Branch, U.S. Food and Drug Administration (FDA)
Lauriel Earley, Ph.D., Senior Scientist, Shape Therapeutics
Jerome Jacques, Principal Scientist, USP
Adriana Kita, Ph.D., Associate Director, Analytical Development, Ultragenyx Pharmaceutical
Rahul Sheth, Ph.D., Senior Scientist 2, Purification Process Development, BioMarin Pharmaceutical

12:30 – 1:15pm: Lunch Break

1:15 – 1:45pm: Setting up for Success: Meeting Regulatory Expectations for Potency Assays

Christopher Miyake, Senior Director, Regulatory Affairs CMC, Sarepta Therapeutics

1:45 – 2:15pm: Development of a Functional Potency Assay for the Characterization of a Novel Krabbe Gene Therapy

Erandi De Silva, Ph.D., Co-founder and Senior Vice President, Product Development, Forge Biologics

2:15 – 2:45pm: Multi-Attribute Potency Assay for AAV Gene Therapy Drug Product

Connie Tsai, Ph.D., Associate Director, Analytical Development Bioassay, Novartis Gene Therapies

2:45 – 3:15pm: Success Story of Luxturna Potency Assay Development and Validation

Ravindra Kumar, Ph.D., Director, Bioassay Lead, Analytical Sciences and Quality Control, Spark Therapeutics

3:15 – 3:30pm: Afternoon Break

3:30 – 4:15pm: Panel Session

Josephine Lembong, Ph.D., Manager, Scientific and Industry Affairs, Alliance for Regenerative Medicine (ARM) (Moderator)
Erandi De Silva, Ph.D., Co-founder and Senior Vice President, Product Development, Forge Biologics
Denise Gavin, Ph.D., Chief, Gene Therapy Branch, U.S. Food and Drug Administration (FDA)
Christopher Miyake, Senior Director, Regulatory Affairs CMC, Sarepta Therapeutics
Ravindra Kumar, Ph.D., Director, Bioassay Lead, Analytical Sciences and Quality Control, Spark Therapeutics
Connie Tsai, Ph.D., Associate Director, Analytical Development Bioassay, Novartis Gene Therapies

4:15 – 4:30pm: Day 1 Concluding Remarks

Josephine Lembong, Ph.D., Manager, Scientific and Industry Affairs, Alliance for Regenerative Medicine (ARM)

Thursday, March 9

7:30 – 8:30am: Registration and Breakfast

8:30 – 8:40am: Opening Remarks

Josephine Lembong, Ph.D., Manager, Scientific and Industry Affairs, Alliance for Regenerative Medicine (ARM)

8:40 – 9:10am: Manufacturing Yields and Impact to Patient Access

Pierre Caloz, Chief Operating Officer, uniQure

9:10 – 9:40am: Quality of AAV Vectors: Impact on Induction and Detection of Immune Responses

Roberto Calcedo, Ph.D., Vice President, Preclinical and Immunology, Affinia Therapeutics

9:40 – 10:10am: The Current and Future State of Choosing qPCR vs. ddPCR in AAV Analytics

Matthew Hewitt, Ph.D., Vice President, Technical Officer CGT and Biologics, Charles River Laboratories

10:10 – 10:40am: Product Comparability and the Transition from qPCR to ddPCR for Characterization of a Novel Krabbe Gene Therapy

Adam Davis, Ph.D., Vice President, Analytical Development, Forge Biologics

10:40 – 11:00am: Morning Break

11:00 – 11:30am: Moving from Vector Genome Titer to Quantification of Vector Genome Integrity by Multiplex dPCR

David Dobnik, Ph.D., Co-founder and Chief Scientific Officer, Niba Labs

11:30am – 12:00pm: Benefits and Challenges of qPCR vs. ddPCR vs. Total Particle Titer Methods

Andrea Hamilton, Ph.D., Associate Director, Quality Control, Gyroscope Therapeutics

12:00 – 12:40pm: Lunch Break

12:40pm – 1:10pm: Regulatory Considerations for AAV Vector Genome and Capsid Titer Determination

Andrew Harmon, Ph.D., Lead Biological Reviewer, Gene Therapy CMC, U.S. Food and Drug Administration (FDA)

1:10 – 1:50pm: Panel Session

Matthew Hewitt, Ph.D., Vice President, Technical Officer CGT and Biologics, Charles River Laboratories (Moderator)
Roberto Calcedo, Ph.D., Vice President, Preclinical and Immunology, Affinia Therapeutics
Pierre Caloz, Chief Operating Officer, uniQure
Adam Davis, Ph.D., Vice President, Analytical Development, Forge Biologics
David Dobnik, Ph.D., Co-founder and Chief Scientific Officer, Niba Labs
Andrea Hamilton, Ph.D., Associate Director, Quality Control, Gyroscope Therapeutics
Andrew Harmon, Ph.D., Lead Biological Reviewer, Gene Therapy CMC, U.S. Food and Drug Administration (FDA)

1:50 – 2:00pm: Day 2 Concluding Remarks

Josephine Lembong, Ph.D., Manager, Scientific and Industry Affairs, Alliance for Regenerative Medicine (ARM)