(692b) Characterization and Design of a 3L Single-Use Bioreactor to Support Process Development and Tech Transfer

The design and characterization of a 3L rigid single-use bioreactor (SUB), to replace existing 3L glass bioreactors, was pursued to further enhance the efficiency of development operations in Merckâ??s Kenilworth biologics facility.

A myriad of bench-scale, rigid, single use bioreactors are commercially available at this time. We required one to replace our current 3L glass bioreactor vessels and meet the diverse requirements of our biologics facility, which supports a continually increasing number of cell culture projects. The new SUB needed to perform like our current bioreactors, so that process development activities would not be impacted. Overall, the SUB was expected to be versatile, robust, and simple to use.

A multi-faceted, iterative approach was used in the development of a new custom 3L SUB, with the following requisites:

• Similar configuration to larger vessels (e.g. drilled tube sparger and rigid baffles)
• Magnetic bottom drive agitation system
• Perfusion ready
• Expanded number of sensor ports and addition lines for flexibility
• Compatible with Automated sampling systems

To characterize the designs, we performed gas transfer (k_La) studies, computational fluid dynamics (CFD) modeling, and cell growth studies with both fed-batch and perfusion processes. The data generated from these studies was used to refine the design and confirm comparability to the glass vessel controls.

Implementation of the customized 3L SUBs has enabled enhanced process development capability by introducing technology to improve operational efficiency.