In this study, an innovative rotating-drum bioreactor was evaluated and compared with a conventional stirred-tank system for CHO cell fed-batch culture, with particular focus on oxygen transfer, hydrodynamic conditions, and overall bioprocess performance. The novel configuration, based on a slowly rotating perforated drum, enabled efficient oxygenation at low rotational speeds, achieving a higher volumetric mass transfer coefficient (k_La = 0.1087 min⁻¹) despite significantly lower tip speeds. This resulted in stable dissolved oxygen (DO) levels (approximately 40%) throughout a 10-day cultivation. Under these operating conditions, the innovative bioreactor promoted enhanced cell growth, achieving a peak viable cell density (VCD) of 2.55 × 10⁷ cells mL⁻¹ and maintaining high viability (around 91.7% on day 10). Monoclonal antibody production reached 1.3 ± 0.09 g L⁻¹, almost doubling the yield obtained in the stirred-tank reactor. The improved outcomes observed in the innovative bioreactor could be associated with the distinct operating and hydrodynamic conditions established by the system configuration. Nevertheless, further studies are needed to better define the operational limits of the system and optimize process conditions. Future investigations should also assess critical quality attributes, including glycosylation patterns, aggregation, fragmentation, and host cell protein contamination, as well as evaluate the performance of the bioreactor at larger scales. © The Author(s) 2026.

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