Continuous viral inactivation at low pH value in antibody manufacturing

Abstract

Due to the evolving biopharmaceutical market, small scale and flexible production processes for continuous antibody manufacturing become more important. Consequently, various continuously operated processing steps like perfusion fermentation or continuous chromatography have been developed. However, no continuously operated viral inactivation at low pH value is available so far. In this article, the coiled flow inverter (CFI) is identified as a suitable reactor for this application and two different design approaches are presented. The logarithmic reduction value (LRV) approach targets at the same LRV in the continuous viral inactivation when compared to current batch operation. The minimum residence time (MRT) approach guarantees a residence time for all molecules entering the continuous viral inactivation of at least the inactivation time of the batch inactivation step. The viral reduction value and the monomer loss during inactivation are characterized for each design approach. Moreover, a linear regression model is developed, which predicts the Bodenstein number as a function of two CFI design parameters under defined boundary conditions. This model allows designing the CFI according to the inactivation time and the chosen design approach.