Cambridge Healthtech Instituteの第4回年次会議
Gene Therapy Manufacturing
2023年3月15 - 16日、CET（中部欧州標準時）
PLENARY SESSION: EMERGING MODALITIES, PLATFORMS, AND TECHNOLOGIES - FROM mRNA TO PROTEINS
基調講演：新興のモダリティ、プラットフォーム、技術 - mRNAからタンパク質へ
Overcoming CMC and Supply Chain Challenges for mRNA Technologies
Thanks to the rapid development of mRNA vaccines for COVID-19, the industry now has the momentum and resources to overcome many of the early CMC challenges and realize its enormous potential. This presentation will discuss the strategies in place to overcome CMC and supply chain challenges for mRNA technologies already and future innovations primed to take it to the next level.
Affinity Proteins for Biotechnological and Medical Purposes
Affinity proteins are crucial for life, for building structures, performing reactions, and for signaling purposes. In life sciences and medicine, affinity proteins are used to generate knowledge, but also for diagnostic and therapeutic purposes. This talk will cover how antibodies and small affinity molecules can be used to map the human proteome, develop diagnostic tools for in vivo visualization as well as efficiently purify therapeutics based on antibodies.
Transition to Sessions12:20
Sponsored Presentation (Sponsor Opportunity Available)12:30
Networking Lunch (Sponsor Opportunity Available)13:00
OPTIMZING PROCESS DEVELOPMENT
High-Throughput Technologies in AAV Production
Bioprocess Engineering Strategies to Enhance Productivity and Yield of the Pinnacle Producer Cell Line Platform, Enabling High Productivity at 2000L Scale
Ultragenyx has developed the Pinnacle PCL producer cell line platform for rAAV product development which is readily scalable to 2000L and has successfully supported multiple clinical gene therapy programs. Bioprocess engineering strategies have been applied to significantly improve productivity and yield, now achieving levels approaching 1E12 gc/ml or greater. The improved Pinnacle PCL platform will be implemented for the manufacturing of an rAAV product to treat Duchenne’s Muscular Dystrophy.
Sponsored Presentation (Opportunity Available)15:35
Refreshment Break in the Exhibit Hall with Poster Viewing16:05
OPTIMZING PROCESS DEVELOPMENT II
Process Optimization for AAV Production - Ensuring High Titer from Lab Scale to Manufacturing Scale
Adeno-associated viruses (AAVs) are currently one of the viral vectors of choice for gene therapy. High titers are necessary to ensure the desired outcome, therefore process optimization has a strong focus on yield improvement. The Upstream tested conditions for enhancing titers through ideal process conditions, the Downstream worked on keeping titers high whilst removing impurities and concentrating the vectors. Together, we established a process feasible for manufacturing at large scales.
Integration of Upstream and Downstream Processes in AAV Production
The biopharmaceutical industry is looking at the concepts of intensification and integration to create more efficient processes. In this presentation, we will provide an overview of the use of perfusion bioreactors to integrate AAV harvesting and clarification processes. Continuous chromatography will then be presented as a tool for AAV capture. Finally, the two examples will be examined for their potential to link upstream and downstream processes.
Quality by Design Process Development for rAAV manufacturing
Recombinant adeno-associated viral vectors (rAAV) are extensively used in gene therapy to introduce a genetic modification, and rAAV have been proven to be extremely effective and safe modalities for in vivo applications. The manufacturing of rAAV often relies on transient transfection of plasmids, and transfection reagents are used to convey plasmids through the plasma membrane. The selection of the best transfection reagents and the optimization of the transfection parameters is therefore key to achieving improved bioprocess productivity, consistency, and scalability. Our quality-by-design approach indicates that FectoVIR AAV (Polyplus) is a very efficient tool for GMP-compliant rAAV production.
Close of Day18:15
Registration and Morning Coffee08:00
RECOVERY AND PURIFICATION OF VIRAL VECTORS
High-Resolution Displacement Anion Exchange Chromatography for the Separation of Empty, Partial, and Full AVVs
Partial AAV capsids are heterogeneous and difficult to separate from full AAV capsids. We demonstrate unparalleled separation of empty, partial, and full capsids with single- and multi-column anion exchange displacement chromatography.
Mechanistic Modeling for Empty and Full Adeno-Associated Viral Capsid Separation
Developed a mechanistic anion exchange chromatography column model to expedite late phase process development for empty and full capsid separation. Modeling the transport of a large molecule, such as rAAV, in chromatography resin is very challenging and was overcome using an advance general rate model, which included variable surface diffusion.
Use of Anion Exchange Chromatography in Weak Partitioning Mode to Provide High Empty AAV Capsid Removal and Product Yields
Scalable methods of full capsid enrichment have often come at the cost of product recovery, thereby increasing the COGS. Here we would like to show that understanding of the AEX chromatography design space led to the identification of weak partitioning mode as an alternative to bind-and-elute. Results show that a full capsid ratio of >80% and a product yield >50% can be robustly achieved when utilizing this method of chromatography.
Sponsored Presentation (Opportunity Available)10:00
Coffee Break in the Exhibit Hall with Poster Viewing10:30
LENTIVIRAL, ONCOLYTIC VIRUS PROCESS DEVELOPMENT
Evolving Approaches to Viral Vector Manufacturing Development
Oxford Biomedica (OXB) is a pioneer in developing products based on viral vectors. To meet the forecast vector demand for gene and cell therapies, OXB has evolved strategies to develop the next-generation manufacturing processes to yield higher vector quantities, suitable product quality attributes, and acceptable cost of goods in order to advance development of a diverse product portfolio including Lenti, Adeno and AAV products which currently present significant challenges.
Single-Step Rapid Chromatographic Purification Process for Clinical Stage Oncolytic VSV-GP
The traditional tools used for protein-based therapeutics often come short in the case of viruses. This is particularly the case when the virus is used for oncolytic purposes rather than as a vaccine wherein the administered dosages are several-fold lower. Another major gap with viral vectors is in our knowledge of the biology and morphology of the therapeutic. The work presented will focus on our efforts in developing novel chromatographic purification techniques complemented with extensive characterization of our virus using a suite of analytics.
Sponsored Presentation (Opportunity Available)12:30
Networking Lunch (Sponsor Opportunity Available)13:00
mRNA PRODUCTION AND MANUFACTURING
Gene Therapy Using Emerging mRNA Technology
mRNA is emerging as a new class of drug that has the potential to play a role in protein replacement therapies. Arcturus has established mRNA/LNP technology platform and applied to rare diseases treatments.
Production and Purification of Archaeal Lipids for Enhanced mRNA Delivery
The use of liposomes and lipid nanoparticles (LNPs) as efficient vehicles for the transport and delivery of APIs is impressively being demonstrated in the ongoing COVID-19 pandemic. Current mRNA-based vaccines are formulated in LNPs to protect the cargo from environmental conditions and allow uptake in cells. Still, current formulations suffer from some drawbacks, like storage stability and rather low transfection efficiencies. I present a novel and scalable strategy for production, purification, and use of very special lipids from extremophilic Archaea for mRNA delivery. Using these lipids in formulations, the transfection efficiency of mRNA could be enhanced more than 80-fold.
Benefits of Microbial Continuous Processing
State-of-the-art recombinant protein production with microbials is conducted in fed-batch cultivation. Switching to continuous processing would impose small-footprint manufacturing and increase the space-time yield compared to fed-batch processing. Still, industry and research struggle in achieving long-term microbial cultivations with stable productivity. Within this presentation, I will address reasons for fluctuating productivity in continuous processes, and discuss opportunities and how to overcome these challenges.
Close of Summit15:20