(507a) Technology Transfer and Scale-Down Models for Mammalian Cell Culture Manufacturing – the Process Knowledge Questions, and the Practical Ones

Fed-batch processing using mammalian cell culture is the most widely used technology for large-scale manufacturing of monoclonal antibodies. Process optimization for the production of monoclonal antibodies is a continued process, potentially involving multiple process generations, and manufacturing sites.

Manufacturing Science groups are a key part of process optimization, as part of their responsibilities is to perform technology transfer from development groups to commercial manufacturing sites, or from a commercial manufacturing site to another. Technology transfer may involve the utilization of lab-scale systems to build process knowledge and to understand performance before manufacturing initiates at large scale. Once commercial scale production is in place, scale-down models are used to monitor and provide real time troubleshooting.

This presentation will focus on the establishment of a scale-down model to support the technology transfer of a new generation of a commercial product to Genentech Vacaville, a multiproduct commercial manufacturing site with the capability of producing monoclonal antibodies in large quantities. Work was performed to optimize the scale-down model, while at the same time provide answers to questions related to manufacturability (e.g., differences in process and impact to run rate, and limitations due to equipment capability). Scale-down model optimization tested the impact of process parameters on performance and product quality, while scale-down model utilization provided answers that enable process fit at large scale.