Workshop A4 - Optimizing Process Conditions for Scalable, Serum-Free Lentivirus Production in Fixed-bed Bioreactors.
Apr 15, 2026 — 11:45 am - 12:45 PMSalle 4
Description
The clinical and commercial success of gene therapies depends on scalable, efficient, and cost-effective viral vector manufacturing platforms. Lentivirus (LV) production faces key challenges that impact both yield and product quality. Adherent, static culture systems (such as multi-trays and roller bottles) support efficient transfection and maintain healthy cells, resulting in high titers and good viral quality. However, scaling up with these systems involves handling large numbers of vessels, which introduces operational complexity and increased aseptic risk. In addition, adherent systems have historically relied on the use of serum containing media, introducing regulatory hurdles.
In response to these challenges, manufacturers have shifted to suspension-based platforms. While enabling large-scale production, this approach faces specific limitations for LV manufacturing, such as:
- High impeller forces degrading fragile LV, resulting in product loss.
- Obstacles related to implementing perfusion culture for continuous harvest, requiring complex and expensive cell-retention devices
- Large crude harvest volumes containing cell debris and other contaminants, placing significant burden on Downstream processing
The scale-X™ fixed-bed bioreactor platform, with its compact design and high productivity, offers a promising solution for viral vector production, particularly for LVs. The bioreactor is scalable by design, while providing a sheltered, low shear environment for adherent cells. This supports up to 10x higher productivity compared to alternative automated systems, while also opening the possibility of operation in perfusion mode for the continuous harvest of secreted LVs under gentler conditions.
A critical enabler of large-scale adherent platforms is the use of serum-free media (SFM), ensuring process consistency, regulatory compliance, and eliminating risks associated with animal-derived components. In this study, a panel of SFM options were screened to identify optimal conditions for HEK293 cell growth and LV production in scale-X fixed-bed bioreactors.
This study was performed in collaboration with the CER Groupe, leveraging their proprietary HEK293 cell line and a model fluorescent LV. The presenter will go through results of this study performed at small scale and in the newly released scale-X nexo bioreactor (0.5m² growth surface area). Results support the relevance of scale-X fixed-bed bioreactors as a high-productivity, low-footprint, cost-efficient manufacturing option for LV manufacturing.
Keywords: fixed-bed bioreactor, gene therapy, LV, serum-free, bioreactors
