Host cell protein (HCP) refers to the protein components in biological products that come from the production cell line, including both the structural proteins of the host cells and the growth factors secreted by the host cells. It is a complex mixture with multiple physiological, chemical and immunological properties and is a major process-related impurity. HCP is a type of heterogeneous protein contamination and an unavoidable impurity in biological products. It may be produced during the recombinant fermentation process or introduced from exogenous substances. If the HCP content exceeds a certain level, it is likely to cause immune reactions or other adverse reactions.
HCP constitutes the main part of process-related impurities in the production of biologics. During the host cell production process, other non-essential proteins in the host cells are released due to life activities such as apoptosis, death, and lysis. Therefore, a large amount of HCP will be produced and remain in the cell culture-based biopharmaceutical process. However, even after multiple complex separation and purification, HCP may be co-purified with products such as biopharmaceuticals, or separated with the sample product, which also makes it difficult to completely separate a large amount of residual HCP. In addition, due to the wide variety of HCPs and the wide range of their molecular weight and abundance, the molecular weight and abundance of many HCPs differ from the target protein molecules by several orders of magnitude, which also increases the difficulty of HCP detection and analysis.
Many HCPs may affect the properties of products and interact with products during production and storage, and even affect the immunogenicity, biological activity and safety of products. With the continuous advancement of HCP characterization technology, the practicality of proteome databases and the continued development of existing genomic information and algorithms, the detection of HCPs will become more and more accurate in the future, and it is expected that the immunogenicity, biological activity, safety of HCPs and their interactions with target proteins will be predicted based on these data. This will better guide standardized production and quantitative risk assessment, and improve the quality and stability of the final product.