Host Cell Protein Profiling in Biopharmaceutical Harvests.

Abstract

Biopharmaceuticals contain residual host cell protein (HCP) impurities, a complex mixture of endogenous proteins from production cell lines such as Chinese hamster ovary (CHO) cells. The composition of HCP impurities at harvest hinges on multiple factors, e.g., identity of cell line, cell density and viability at harvest, or other process parameters. Two-dimensional differential gel electrophoresis (2-D DIGE) was used to compare HCP in 15 null cell culture harvest supernatants, which are representative for a wide range of manufacturing processes of therapeutic antibodies, using five different CHO cell lines. Numerical metrics were developed to quantitatively compare HCP composition, which may be used to assess the suitability of a platform HCP assay standard for a new product or to assess the impact of process changes. A very similar HCP composition was found for the 15 analyzed CHO null cell culture harvests, demonstrating that even the wide range of applied manufacturing processes did not have a strong influence on the HCP impurities.