In recent years, continuous Virus Inactivation (cVI) has attracted significant attention in the biopharmaceutical industry due to the growing interest in end-to-end continuous downstream processing. Introduction of cVI allows continuous downstream operation while reducing footprint and operational handling. While a rather simple batch unit operation, developing a continuous unit operation requires integrating an in-line titration along with a tightly controlled residence time element to effectively inactivate viruses and reduce the risk of aggregation. Increased examination from a viral clearance perspective requires a robust, inline pH adjustment step that has a short response time with a stable pH output. This work will present on the development of an automated in-line titration using a closed feedback loop to control pH. Furthermore, a tubular reactor is used to create a narrow Residence Time Distribution (RTD) to ensure material remains at low pH for sufficient time required for inactivation. Previous work in the area has focused on the two aspects of cVI separately, in-line titration and designing a residence time reactor. However, the hardware used for in-line titration introduces dispersion which needs to be considered to determine residence time at low pH. This work explores the relationship between the hardware, feedback control and reactor design to ensure a narrow RTD at low pH to guarantee viral inactivation for patient safety.

Complexities of designing and automating a continuous virus inactivation unit operation

2019 Spring National Meeting

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