Host cell proteins in biologics development: Identification, quantitation and risk assessment
Article first published online: 22 APR 2009
Copyright © 2009 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 103, Issue 3, pages 446–458, 15 June 2009
How to Cite
Wang, X., Hunter, A. K. and Mozier, N. M. (2009), Host cell proteins in biologics development: Identification, quantitation and risk assessment. Biotechnol. Bioeng., 103: 446–458. doi: 10.1002/bit.22304
- Issue published online: 22 APR 2009
- Article first published online: 22 APR 2009
- Manuscript Accepted: 12 FEB 2009
- Manuscript Revised: 6 FEB 2009
- Manuscript Received: 7 NOV 2008
- host cell proteins;
- Western blot;
Host cell proteins (HCPs) are those produced or encoded by the organisms and unrelated to the intended recombinant product. Some are necessary for growth, survival, and normal cellular processing whereas others may be non-essential, simply carried along as baggage. Like the recombinant product, HCPs may also be modified by the host with a number of post-translational modifications. Regardless of the utility, or lack thereof, HCPs are undesirable in the final drug substance. Though commonly present in small quantities (parts per million expressed as nanograms per milligrams of the intended recombinant protein) much effort and cost is expended by industry to remove them. The purpose of this review is to summarize what is of relevance in regards to the biology, the impact of genomics and proteomics on HCP evaluation, the regulatory expectations, analytical approaches, and various methodologies to remove HCPs with bioprocessing. Historical data, bioinformatics approaches and industrial case study examples are provided. Finally, a proposal for a risk assessment tool is provided which brings these facets together and proposes a means for manufacturers to classify and organize a control strategy leading to meaningful product specifications. Biotechnol. Bioeng. 2009;103: 446–458. © 2009 Wiley Periodicals, Inc.