Modernizing clearance and quantification of host-cell proteins in mAb manufacture

To Improve reliability and quality assurance of the manufacturing processes through purification of monoclonal antibodies(mAbs) made by Chinese Hamster Ovary(CHO)

Industry Need

Host-cell proteins (HCPs) are a major class of impurities in biopharmaceutical manufacturing.
The removal of HCPs is complicated by the need to reduce both the total HCP content and the amounts of individual species that can be harmful to the product and/or patients.

Approach

Led by the University of Delaware, the team will develop new and complementary technologies for achieving and monitoring the removal of host-cell proteins (HCPs) in purification of monoclonal antibodies (mAbs) made by Chinese hamster ovary (CHO) cells.

Impacts

characterize HCP aggregates that contribute to HCP persistence in process streams and hence develop new methods to improve their removal.

HCP removal in multiple applications by employing novel LigaGuardTM materials that specifically capture CHO HCPs.

Benchmark and standardize liquid chromatography-mass spectrometry (LC-MS) technology to monitor HCP levels in biomanufacturing

This project will address the need to remove HCPs and to measure the amounts of individual HCPs in process streams. Once completed, the project will enable more robust processes in which HCP removal is achieved and monitored efficiently and in versatile process configurations.

This will be accomplished by improving HCP removal in multiple applications by employing novel LigaGuardTM materials that specifically capture CHO HCPs while allowing the mAb product to flow through unbound, characterizing HCP aggregates that contribute to HCP persistence in process streams and develop new methods to improve their removal, and benchmarking and standardizing liquid chromatography-mass spectrometry (LC-MS) technology to monitor HCP levels in biomanufacturing.

Value Statement/Outcomes

By utilizing LigaGuard™ materials for targeted capture, this initiative significantly improves host-cell protein (HCP) removal, reducing the risk of batch failures that can cost manufacturers between $1M and $5M per lost lot. The project’s standardization of LC-MS technology replaces traditional days-long ELISA testing with a species-specific monitoring system that provides detailed results in just hours, accelerating the purification validation cycle. Together, these advancements enable a more efficient flow-through process that maintains ultra-low impurity levels, directly protecting product margins and reducing the time required for complex CMC (Chemistry, Manufacturing, and Controls) regulatory reporting.

Posters

Lenhoff, A., Conference Participant, 5.2-133: Modernizing Clearance and Quantification of Host-Cell Proteins in mAb Manufacture, NIIMBL National Meeting, Washington, D.C., June 26, 2025.

Presentations

Lenhoff, A., Understanding and Mitigating Persistence of CHO Host-Cell Proteins in MAb Bioprocessing, ISPPP 2023 (Intl. Symposium on Separations of Proteins, Peptides and Polynucleotides, Vienna, Austria, November 7, 2023.

Menegatti, S., Mouchahoir, T., Lenhoff, A., Cramer, S., Bill, J., Li, S. X., Xu, X., Tully, T., & Crapanzano, M., Modernizing Clearance and Quantification of Host-Cell Proteins in mAb Manufacture, NIIMBL National Meeting, Washington, DC, June 27, 2024.