Effective strategies for host cell protein clearance in downstream processing of monoclonal antibodies and Fc-fusion proteins

- Effective HCP removing strategies in downstream processing of antibodies and Fc-fusions are reviewed.
- The discussed strategies can enhance the chance of meeting the drug substance specifications for residual HCP.
- These strategies can be applied at different stages of the standard downstream process.
- Data showing the relative HCP removing capacity of the discussed strategies are provided.

Recombinant therapeutic proteins are typically produced through cell culture process. Host cell proteins (HCPs) are endogenous proteins derived from the host cells used for such bioproduction. HCPs form a major class of process-related impurities and even at low levels they can potentially compromise the safety and efficacy of biopharmaceuticals. Therefore, they need to be adequately removed via the downstream process. HCPs are complex mixtures with diverse physiochemical properties, and certain subpopulations can bind to the intended product. Hence reducing them to the generally accepted level can be challenging. This article reviews effective HCP removing strategies at different stages of downstream process for monoclonal antibodies and Fc-fusion proteins. When used in combination, these strategies can greatly enhance the chance of meeting the drug substance specifications for residual HCP.