Navigating evolving regulatory CMC guidance in the AAV gene therapy field

After postdoctoral research training with Dr. James M. Wilson at Institute of Human Gene Therapy, University of Pennsylvania, Yan had spent over 15 years in global contract testing organizations (WuXi AppTec and Charles River Laboratories) to provide scientific leadership to Biologics testing services with the strong focus on cell and gene therapy industry as well as a global contract development and manufacturing organization (Fujifilm Diosynth Biotechnologies) to design cell and gene therapy product development programs from clinical to commercial manufacturing. In 2020, Yan joined Spirovant Sciences, Inc. to lead the analytical development and develop CMC strategy of a novel serotype AAV based in vivo gene therapy product for IND submission. Since 2022, Yan has been working with CMC, regulatory, quality, supply, and commercial teams at CSL Behring to support commercial launch of an AAV gene therapy product as well as manufacturing process and analytical methods transfer to a second site for future registration. Yan received a PhD in Microbiology and Molecular Genetics from University of California, Irvine, and a BA in Molecular Biology from University of Science & Technology of China. She is a leading author and co-author of numerous publications in peer-reviewed scientific journals and a patent holder.

Christine Le Bec joined Sensorion Pharma in early 2020 as Head of CMC Gene Therapy. She is responsible for all CMC activities, including pre-clinical development, CMC transfer to CMOS, manufacturing and supplying of Phase 1 and 2 clinical trails. Before joining Sensorion Pharma, she worked for more than 20 years at Genethon in the field of Gene Therapy vectors (AAV, Lentivirus, Baculovirus) for rare diseases. She has a strong expertise in the development, qualification, validation of analytical methods for product characterization, release testing of gene therapy products and in stability studies. She has also a solid knowledge of International regulations and reviewing CMC documents for clinical trial applications.

Michael Brewer is the Director, Global Principal Consultant, Regulatory for the BioProduction Group (BPG) at Thermo Fisher Scientific. In this role, Michael is responsible for providing global support to BioProduction customers and serving as the regulatory thought leader and expert across all technology areas within BPD. Prior to moving to this role, he led the Pharma Analytics business, a team responsible for development and commercialization of testing applications for Microbiology, Analytical Sciences and Quality control. The products are fully integrated, solutions for Glycan profiling, Bacterial and Fungal identification, Mycoplasma and Viral detection and host cell DNA and protein quantitation. Michael has over 30 years’ experience in the Biopharma industry, including, Scios, Synergen and Amgen in a variety of roles including Discovery Research, Analytical Sciences and Quality Control. Prior to joining Thermo Fisher Scientific, he led a group at Amgen that developed qualified, validated and implemented molecular methods for host cell DNA quantitation, contaminant (Mycoplasma, Virus and Bacteria) detection, contaminant identification, strain typing and genotypic verification of production cell lines. Additionally, his group supported regulatory submissions including IND, NDA, and CMC updates, Regulatory inspections, NC/CAPA investigations, contamination investigations and remediation and developed regulatory strategy for implementation of new methods.

Alexis has worked in CMC regulatory affairs for more than 17 years and focused solely on gene/cell therapy products for the last 11+ years. She is currently a freelance regulatory consultant as Lex Regulatory Ltd and works with a number of organizations developing advanced therapies. A large proportion of her experience is with gene therapy products. She has accumulated knowledge from more than 25 years in science-related roles and finds the complexities and challenges of advanced therapies very rewarding.

Christina Fuentes is a Senior Consultant at Dark Horse Consulting Group where she provides technical expertise in Cell and Gene Therapy to help clients address unique challenges in the field. Her specialties include supporting clients utilizing engineered nucleases for gene modification and AAV for in vivo therapies. Prior to joining Dark Horse Consulting, Christina completed her PhD at University of California, Berkeley in David Schaffer’s lab where she engineered systems to enhance cell and gene therapies, including the development of a self-inactivating AAV mediated CRISPR-Cas system for therapeutic genome editing in vivo. Dr. Fuentes co-authored the first externally prepared proposed draft guidance on “Testing of Adeno-Associated Viral (AAV) Vector-Based Human Gene Therapy Products for Empty Capsid During Product Manufacture” which was formally submitted to the FDA for consideration on May 15, 2022. Most recently, Christina co-authored a white paper titled “Beyond Empty and Full: Understanding Heterogeneity in rAAV Products and Impurities.” This document details the importance of product characterization  and heterogeneity in product-related impurities to improve product understanding and inform manufacturing strategy.