MAb manufacturing platform processes have evolved that are capable of achieving target levels of key impurities, including HCPs, DNA and product-related impurities such as HMW aggregates. The HCP assays used – typically ELISA methods – leave open the possibility that although overall HCP levels may meet target specifications, the residual concentrations of individual HCPs may be undesirably high.
We propose to develop a consistent, comprehensive approach to identify and clear problematic host-cell proteins (HCPs) in monoclonal antibody (mAb) biomanufacturing.
Database of CHO host cell proteins (HCPs) and their biophysical properties, particularly those that are difficult to remove during manufacturing.
Database will include characterization of HCP interactions with mAb products and typical resins.
Improved PepMix(es) for capturing a broad spectrum of HCPs from CHO cell lines, including the clearance of problematic HCPs.
By implementing peptide-ligand resins and a comprehensive CHO HCP database, an organization could reduce downstream purification costs and failed campaign risks by millions of dollars, enabling higher mAb yields (>85%), improved process robustness, and accelerated clinical and commercial launches.
Database of CHO HCPs, including patterns of removal in typical mAb platform process steps.
Knowledge base of HCP interactions with mAb products and significance for HCP tracking in existing commercial processes.
Resins based on peptide ligands for capturing broad spectrum of HCPs from CHO cell lines.
Oh, Y. H., Becker, M. L., Mendola, K. M., Choe, L. H., Min, L., Lee, K. H., Yigzaw, Y., Seay, A., Bill, J., Li, X., Roush, D. J., Cramer, S. M., Menegatti, S., & Lenhoff, A. M. (2024). Factors affecting product association as a mechanism of host-cell protein persistence in bioprocessing. Biotechnology and Bioengineering, 121(4), 1284–1297. https://doi.org/10.1002/bit.28658
Becker, M., Oh, Y., Mendola, K., Seay, A., Li, S. X., Roush, D., Cramer, S., Menegatti, S., & Lenhoff, A., Biophysical Characterization of Problematic Host Cell Proteins in Monoclonal Antibody Processes, ACS National Meeting, Virtual, August 26, 2021.
Lenhoff, A., Identification and Impact of Individual Host-Cell Proteins in CHO-Based Biomanufacturing, Bioprocessing Summit, Boston, MA, August 13, 2019.
Lenhoff, A., Mechanisms of Persistence of CHO Host-Cell Proteins in mAb Bioprocessing, Bioprocessing Summit, Boston, MA, August 17, 2021.
Lenhoff, A., Menegatti, S., Yigzaw, Y., Roush, D., & Cramer, S., Identification, Characterization and Removal of Host-Cell Proteins in Chinese Hamster Ovary Monoclonal Antibody Biomanufacturing Processes, NIIMBL National Meeting, Washington, DC, June 28, 2019.
Lenhoff, A., Patterns and Determinants of Persistence of CHO Host-Cell Proteins in mAb Bioprocessing, Bioprocessing Summit, Virtual, August 25, 2020.
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.
Oh, Y., Mendola, K., Becker, M., Choe, L., Lee, K., Yigzaw, Y., Roush, D., Cramer, S., Menegatti, S., & Lenhoff, A., Problematic CHO host-cell proteins: Identification and binding to monoclonal antibodies, Winter Research Review, Newark, DE, January 22, 2020.
Oh, Y., Mendola, K., Becker, M., Choe, L., Roush, D., Yigzaw, Y., Lee, K., & Lenhoff, A., Binding of CHO host-cell proteins to monoclonal antibodies, ACS National Meeting, Philadelphia, PA, March 22, 2020.
Oh, Y., Mendola, K., Choe, L., Lee, K., Seay, A., Roush, D., Cramer, S., Menegatti, S., & Lenhoff, A., Aggregate- and particle-associated host-cell proteins in monoclonal antibody bioprocessing, ACS National Meeting, Virtual, August 22, 2021.
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University of Delaware
Genentech, Inc.
Merck Sharp & Dohme LLC
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Rensselaer Polytechnic Institute
Repligen Corporation
