Scalable Bioprocessing Strategies For Intensified Viral Vector Production In HEK293 Cell Culture

Scalability is crucial in bioprocessing to ensure consistency in product quality, yield, and cell growth kinetics when translating from small to large scales. This work explores how intensified cell perfusion systems paired with specialized cell culture media can meet this challenge for viral vector production in HEK293 cell cultures.
A key finding is that combining media optimization with the avoidance of pH control significantly enhances cell growth, viability, and metabolite control. Specifically, this approach minimizes lactate buildup and achieves a threefold reduction in ammonia accumulation. The optimized process supported high cell densities, up to 1.1×108 cells/mL, with a low cell-specific perfusion rate (CSPR) of only 25 μL/cell/day.
By maintaining precise control of bioprocess parameters, the study achieved consistent HEK293 cell metabolic profiles and viral vector production across scales, successfully reproducing results from 50 mL to 5 L. The resulting integrated approach offers a robust and versatile blueprint for improving viral vector manufacturing workflows.
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