Comparability of Five Alternative AAV9 Downstream Processes, from Ultracentrifugation to Chromatography

Life Sciences, Pharma Manufacturing & Supply Chain, Drug Discovery & Development, Laboratory Technology, Cell and Gene Therapy,
  • Thursday, June 27, 2024 | 10am EDT (NA) / 3pm BST (UK) / 4pm CEST (EU-Central)
  • 60 min

Improved analytical methods are helping improve the understanding of capsid heterogeneity in adeno-associated virus (AAV) therapeutic preparations. This understanding allows the development of manufacturing processes that produce AAV therapeutics with fewer non-functional capsids.

In this webinar, the speakers will present the results of a five-arm AAV9 comparability protocol that includes four alternative two-column downstream processes at 50-L scale and an ultracentrifugation (UC) process at 200-L scale. The UC process is the gold standard for functional capsid purification.

The expert speakers will outline simplified processes for both the capture and the empty/full (E/F) separation steps, including various combinations of cation exchange chromatography (CEX) and anion exchange chromatography (AEX) monoliths with different gradient types, as well as a process using an affinity resin and AEX monolith.

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Also, the speakers will cover the analytical comparability of the drug substance lots, assessment of vector yields, host–cell proteins, plasmid and host-cell deoxyribonucleic acid (DNA) levels; capsid content by sedimentation-velocity analytical UC, charge detection mass spectrometry and mass photometry; vector protein purity by capillary electrophoresis; aggregation by size-exclusion chromatography; vector DNA purity by next-generation sequencing; potency by in vitro enhanced green fluorescent protein (eGFP) expression tests; and capsid protein charge heterogeneity and intact-capsid isoelectric point (pI) by capillary isoelectric focusing.

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Register for this webinar today to gain insights into the production of AAV therapeutics using enhanced analytical methods with their role in reducing capsid heterogeneity.

Speakers

Aleš Štrancar, Sartorius BIA Separations

Aleš Štrancar, Executive Managing Director, Sartorius BIA Separations

Aleš Štrancar is the Executive Managing Director of Sartorius BIA Separations since its founding in 1998.

Aleš is one of the main inventors of the CIM Convective Interaction Media® monolithic columns technology and the co-inventor of many analytical methods, including pDNA, mRNA, AAV, Adeno and other viruses.

He has co-developed several DSP processes, including pDNA for Boehringer Ingelheim and AAV for AveXis/Novartis. Aleš is the author or co-author of more than 100 scientific papers dealing with separation and purification technologies and the co-author of several granted patents.

Message Presenter
Joe Balleydier, Advanced Medicine Partners

Joe Balleydier, Senior Vice President of Research and Development, Advanced Medicine Partners

Joe Balleydier is the Senior Vice President of Research and Development for Advanced Medicine Partners. Joe has 29 years of biopharmaceutical experience with eight years of AAV-based gene therapy experience. Joe developed the upstream process for Zolgensma while at AveXis/Novartis and led the process development efforts at Jaguar Gene Therapy. Joe began his career with Monsanto and had expanded roles with Pfizer, Amgen and Novartis Vaccines.

Message Presenter
Mike Hatfield,Advanced Medicine Partners

Mike Hatfield, Senior Director of Research and Development, Advanced Medicine Partners

Mike Hatfield is the Senior Director of Research and Development at Advanced Medicine Partners and Former Scientific Lead of downstream process development for Zolgensma at Avexis/Novartis and AAV therapeutics at Jaguar Gene Therapy. Mike has worked in the biopharmaceutical industry for 32 years, including 14 years with oncolytic viruses and 10 years with viral gene therapy. Oncolytic viruses included adenoviruses at Onyx Pharmaceuticals and vaccinia virus at Jennerex Biotherapeutics. Early in his career, he studied FGF-targeted polysine/DNA complexes at Selective Genetics for bone fractures and diabetic ulcers. He has also led pharmacology/toxicology, project management, fill/finish, analytical development and clinical supply chain groups.

Message Presenter

Who Should Attend?

This webinar will appeal to professionals in the following fields:

  • CMC
  • Process development
  • Analytical development
  • MSAT

What You Will Learn

Attendees will learn about:

  • Two-column processes producing 90 to 93 percent full capsids at drug substance compared to 94 percent for the ultracentrifugation (UC) process based on sedimentation velocity analytical ultracentrifugation (SV-AUC) analyses
  • How 84 to 87 percent of the encapsidated deoxyribonucleic acid (DNA) sequences in the drug-substances were full-length expression cassettes capable of expressing enhanced green fluorescent protein (eGFP) based on long-read next-generation sequencing (NGS)
  • The potencies of the drug substances from two-column processes being equivalent and potentially greater than the UC-purified drug substance
  • How the two-column processes can be more readily scaled to 500-L and 1000-L bioreactors than the UC process

Xtalks Partners

Sartorius

Sartorius BIA Separations is developing the best-in-class analytical and preparative chromatographic solutions for Gene Therapy and Vaccines spaces. CIM column, utilized in hundreds of clinical batches, are setting the standard of manufacturing highly complex AAV, Adeno, pDNA, mRNA, VLP, Viruses, Viral Vaccines, LNP, Exosomes and bacteriophages products. PATfix in-process LC system with multidetector set-up aims to enhance bioprocess understanding and implies a holistic approach to ensure that quality is built into products by design.

Advanced Medicine Partners

Advanced Medicine Partners delivers what patients deserve and what regulators expect.

The company provides partners with process development, manufacturing, analytical development and testing for advanced therapy products, specializing in viral vectors for gene and cell therapies. Advanced Medicine Partners leverages one of the most experienced genetic medicines teams in the industry, and its exclusive manufacturing platform consistently produces yields that are among the highest in the industry and purity profiles that push the boundaries of what’s possible.

Advanced Medicine Partners’ proprietary adeno-associated virus (AAV) manufacturing process minimizes impurities and consistently generates industry-leading functional full capsid ratios. This manufacturing process prioritizes patient safety while reducing cost of goods. The company brings extensive operational experience and has manufactured upwards of 350 total non-GMP batches and supplied over 20 preclinical studies, including IND-enabling efficacy and GLP toxicology studies. The team has led CMC efforts for three globally approved gene therapies.

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