Host Cell Proteins: The Hidden Side of Biosimilarity Assessment.

ABSTRACT

One major concern with biosimilars is that small differences compared with reference products might lead to unforeseen immunogenicity, thus affecting patient safety and drug efficacy. Differences could be due to either post-translational modifications of the therapeutic protein and/or to traces of impurities from the manufacturing process. The results presented in this communication illustrate the efforts to assess "biosimilarity" of a biosimilar candidate to a reference product for a specific group of process-related impurities, the host cell proteins (HCP). Extensive characterization of HCP in the drug substance of a biosimilar candidate revealed the identity of HCP copurifying with the protein of interest and guided process development to improve overall HCP clearance in the downstream process. The data presented illustrate the challenge of matching the reference product on either quantitative or qualitative aspects of HCP impurities.