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Challenges in the assay development for host cell protein for biologics

Most of the process-related impurities are critical quality attributes (CQAs) in biologics development and production. These include host cell proteins, DNA, microbial contaminants, affinity ligands used in the purification and others. The level of those impurities must be monitored and controlled in the process development and later in the production to make sure the desired product quality. In the presentation, we focus on the analytical method of HCP, one of the most challenging impurities to monitor, and introduce our strategy for designing a comprehensive HCP risk mitigation.

The most widely used method to monitor HCP levels in biologics is Enzyme-Linked ImmunoSorbent Assay (ELISA). It uses a set of specially designed polyclonal antibodies to detect as many HCPs as possible. Due to the nature of multi-analyte targets and the changes in HCP populations during the downstream purification processes, the selection of a right ELISA has been a challenge. We share our recent study on how the performance of the HCP ELISA will be evaluated. In the study we tested HCP ELISA kits with dilution linearity in process samples, sample matrix effect, limit of detection and quantitation (LOD and LOQ), and coverage analysis of ELISA antibody. We have detected HCP levels in several commercial drug substances using different HCP ELISA kits to understand sample dependency of each HCP ELISA kit performance.

We also look into a question, if one should consider “in-house” or “out-sourced” strategy to build capability of HCP analysis to mitigate the HCP risk and maximize the drug development efficiency.

Joe Hirano, PhD
Program manager, Imaging and Western Blotting, Cytiva

Joe Hirano is a program manager at Cytiva based in Uppsala, Sweden, where he coordinates products and their applications between R&D and external collaborators to support customers.

Since joining the company in 2000, Joe has been working with genomics, protein research, and biomanufacturing products, including electrophoresis, Western blot, imaging, and upstream and downstream bioprocess products. His current focus is on the analysis of host cell protein and other impurities. Before joining the biopharma industry, Joe studied marine biology as a research scientist.