(642c) Case Study: Investigation of the Improved Fed-Batch Platform for the Selection of a Schering-Plough Monoclonal Antibody Cell Line to Support the Manufacturing of Tox and Early Clinical Supplies

The major challenges in the development of a robust monoclonal antibody (mAb) production process are: (1) the selection of a production cell line that is susceptible to process optimization and is scaleable for large scale manufacturing; (2) the identification of a high yielding production process with a compressed timeline.

To address the compressed timeline for clonal selection and process development, it is necessary to implement the established platform process into clonal selection in order to meet the timeline for Tox and early clinical drug supply requirements. This is followed by the development of a new production platform to achieve a high yielding process to supply for late-stage clinical and commercial supply demand. The goals of the development team are (1) to identify the best production clone using the existing base medium that is commercially available to produce the toxicology and Phase 1/2 clinical supplies rapidly; (2) to determine whether the best production cell line selected for Tox and early clinical production would be different if the selection screening process utilizes the newly developed base medium; (3) to demonstrate enhanced mAb productivity.

This work describes the selection of a high-yielding production cell line and the development of a production process to provide drug supply for Toxicology and clinical studies of a Schering-Plough monoclonal antibodies program. This work examined the production potential of 10 candidate cell lines in the existing commercially available production base medium platform, and in the in-house developed Schering-Plough proprietary base medium platform. In this investigation, ten expressing clones were propagated and maintained in both base medium platforms. The selection of the final production clone and identification of the production process suitable for Tox and clinical manufacturing were determined within 3 months. During this duration, a total of four rounds of evaluation assessment in both medium platforms were conducted using bioreactor tubes, shake flasks, and small-scale bioreactors. Moreover, cells of different in vitro age were tested to assess cell age-related and cell bank preparation effects. The selected cell line was determined to be the best performer in both media. Volumetric productivity in the optimized processes yield 2 times higher titer, as compared to the existing base medium platform.