Commercial-scale manufacture of lentivirus for <em>ex vivo</em> and <em>in vivo</em> therapies
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Commercial-scale manufacture of lentivirus for ex vivo and in vivo therapies

Thursday 08:00 PDT / 11:00 EDT / 15:00 GMT / 16:00 CET
Commercial-scale manufacture of lentivirus for <em>ex vivo</em> and <em>in vivo</em> therapies

There are three key current challenges that the cell and gene therapy field is facing in the manufacture of CAR-T cells: one is raw material production, the second is the production of enough viral vector to meet demand, and the third is the inherent variability in cellular starting material. The common approach to generating fragile envelope viruses like lentiviral vectors (LVs) is based on transient transfection. LV is also produced by inducible expression system using stable producer cell lines. In this study we will present proof-of-concept studies on the development of a perfusion-intensified (by 50-fold) process for envelope virus-based vector manufacturing, providing sufficient LV to cater for large patient populations.

As the field of LVs is progressing toward large-scale manufacturing to generate sufficient functional lentivirus for treating patients, scalability and consistency are important aspects to consider. The TFDF perfusion system that is adapted to the fragility of envelope viruses can be scaled to industrial-size production bioreactors where the LVs are harvested continuously and pass into the TFF or capture step of downstream purification. This greatly reduces hold time, reducing loss of envelope virus functionality.

  • Understanding how KrosFlo TFDF can increase productivity and yield for lentivirus manufacturing
  • Improving and simplifying production and manufacturing capacity using a closed automated continuous virus harvest strategy
  • Addressing scalability, yield, labor, and cost challenges in using suspension and adherent cell line platforms for large-scale continuous manufacturing of LVs using TFDF
  • Developing an agnostic platform solution for envelope-based viral vector production and continuous clarification
  • Targeting affordable viral vector manufacturing by reducing cost per dose
Rachel Legmann
Rachel Legmann
Senior Director of Technology, Gene Therapy at Repligen

Rachel has more than 25 years of experience in the field of scalable biologics and gene therapy manufacturing of therapeutic products, viral vectors and proteins for gene therapy and biologics. She completed her Ph.D. in Food Engineering and Biotechnology at the Technion-Israel Institute of Technology, Israel. Rachel joined Repligen in 2021 as a subject matter expert leading the global gene therapy organization helping customers achieve their technical and operational objectives in their manufacturing of vector-based therapeutics and vaccines with a focus on gene therapy processes including upstream, downstream, analytics and scalability. In addition to supporting global customers and building high level networks, Rachel is supporting various internal cross-functional activities and external collaborations. Prior to joining Repligen, Rachel held several scientific and leadership roles at Microbiology and Molecular Genetics department at Harvard Medical School, CRO SBH Sciences, Seahorse Biosciences part of Agilent, CDMO Goodwin Biotechnology and Pall Corp part of Danaher.

Michelle Yen Tran
Michelle Yen Tran
Process Development Scientist at McGill University

Michelle is a researcher with experience in cell culture engineering, purification techniques, and functional characterization and analytics for viral vectors and recombinant proteins. She completed her PhD in Biological and Biomedical Engineering under the supervision of Dr. Amine Kamen in the Viral Vectors and Vaccines Bioprocessing group at McGill University. Her PhD project focused on process intensification strategies that contribute to increasing the production of lentiviral vectors in HEK293 suspension cells at large-scale while mitigating the loss of functionality. Prior to her graduate program, Michelle developed scalable purification methods for therapeutic recombinant enzymes from CHO cells and gene therapy vectors from Adeno-Associated Viruses in the Purification Process Development group at BioMarin Pharmaceutical Inc.