Analysis of Host Cell Proteins in Protein A Eluates of Therapeutic Proteins

Host cell proteins (HCPs) are one of the major process-related impurities of therapeutic protein production based on biological systems such as Chinese hamster ovary (CHO) cells. For clinical application of biopharmaceuticals, the control of HCP is crucial for product stability, product quality and patient safety. This project aims to focus on the latter concern. A holistic approach was chosen to investigate the immunogenic potential of proteins contained in a culture harvest from a CHO null cell line. A 2D fractionation strategy based on precipitation and chromatography was applied. LC-MS/MS and an in vitro dendritic cell (DC) assay was then used to analyze the HCPs within the fractions. All fractions were able to activate the DCs. Some fractions, however, triggered a stronger response in DCs indicating the presence of HCPs with a higher immunogenic capability. These data provide various insights into the immunogenic potential of CHO-derived impurities. Ultimately, this approach shall build the basis of a risk-based approach for evaluating HCPs appearing in final drug products.

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Prof. Dr. Thomas Villiger

Team Leader