Guidelines for Developing a High Cell Density Cryopreservation Process

Biopharmaceutical manufacturers are leveraging several approaches to intensify processes with a goal of improving efficiency and productivity and reducing costs — all while ensuring the highest quality standards. The upstream workflow offers several opportunities to apply next generation technologies and methods to achieve these important goals. In this white paper we discuss integration of high cell density cryopreservation (HCDC) in the seed train and explore key considerations for developing a cryopreservation process including choice of cryoprotectant and freezing techniques.

Use of HCDC is a proven strategy for intensifying the upstream workflow. This white paper demonstrates that HCDC can compress and accelerate the seed train and offers the advantage of closed processing. Bioreactors seeded with cells cryopreserved using HCDC bags can offer better reproducibility in seed train expansion and allows decoupling of expansion and batch production, enabling distribution of cells from a central expansion facility to global, decentralized production facilities. While each cell line may respond to the HCDC process in a slightly different manner, guidelines for the recommended concentration of DMSO and the freezing process are provided, offering a foundation for development of cell line-specific conditions.