Host cell proteins (HCPs) are process-related impurities that may copurify with biopharmaceutical drug products. Within this class of impurities there are some that are more problematic. These problematic HCPs can be considered high-risk and can include those that are immunogenic, biologically active, or enzymatically active with the potential to degrade either product molecules or excipients used in formulation. Some have been shown to be difficult to remove by purification. Why should the biopharmaceutical industry worry about these high-risk HCPs? What approach could be taken to understand the origin of its copurification and address these high-risk HCPs? To answer these questions, the BioPhorum HCP Workstream initiated a collaboration among its 26-company team with the goal of industry alignment around high-risk HCPs.
The information gathered through literature searches, company experiences, and surveys was used to compile a list of frequently seen problematic/high-risk HCPs. These high-risk HCPs were further classified based on their potential impact into different risk categories. A step-by-step recommendation is provided for establishing a comprehensive control strategy based on risk assessments for monitoring and/or eliminating the known impurity from the process that would be beneficial to the biopharmaceutical industry.
The database available on the BioPhorum website and paper, published in Biotechnology and Bioengineering, provide a comprehensive review/list of potential problematic HCPs that could impact the safety, efficacy, and quality aspects of CHO-produced biologics during their development and manufacturing. It provides a great reference on the best practice and control strategy for “high-risk” HCPs” in the biopharmaceutical industry.