Host cell proteins in biologics development: Identification, quantitation and risk assessment

@article{Wang2009HostCP,
  title={Host cell proteins in biologics development: Identification, quantitation and risk assessment},
  author={Xing Wang and Alan K. Hunter and Ned M. Mozier},
  journal={Biotechnology and Bioengineering},
  year={2009},
  volume={103}
}
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… Expand
Host cell proteins in biotechnology‐derived products: A risk assessment framework
TLDR
Factors to be considered in an assessment of risk of residual host cell protein(s) detected and identified in the drug product will lead to an overall risk assessment that informs decision‐making around how to control the levels of host cell proteins. Expand
The future of host cell protein (HCP) identification during process development and manufacturing linked to a risk‐based management for their control
TLDR
A nascent approach to risk assessment of HCPs based upon such data is described, drawing attention to timeliness in relation to biosimilar initiatives. Expand
Identification of a host cell protein impurity in therapeutic protein, P1
TLDR
The presence of CHO‐catalase subunit protein as an impurity present in purified P1 protein, P1 was identified and the identity confirmed using liquid chromatography‐mass spectrometry (LC‐MS/MS) analysis. Expand
Targeted Capture of Chinese Hamster Ovary Host Cell Proteins: Peptide Ligand Discovery
TLDR
Development of synthetic peptide ligands capable of capturing a broad spectrum of Chinese hamster ovary (CHO) HCPs with a combination of peptide species that allow for advanced mixed-mode binding is described. Expand
Improved HCP Quantitation By Minimizing Antibody Cross-Reactivity to Target Proteins
level: interMediate H ost cell proteins (HCPs) are process-related impurities derived from a host cell expression system that may be present in trace amounts in a final drug substance. DuringExpand
Toward the complete characterization of host cell proteins in biotherapeutics via affinity depletions, LC-MS/MS, and multivariate analysis
TLDR
Clustering analysis using these measures of dissimilarity between HCP profiles enabled high resolution differentiation of commercial grade monoclonal antibody samples generated from different cell lines, cell culture, and purification processes. Expand
Host cell protein analysis in therapeutic protein bioprocessing – methods and applications
TLDR
Different methods for the comparison of bioprocessing strategies during scale‐up and purification development are compared and include immunospecific methods, such as ELISA, western blot, and threshold, and non‐specific methods,such as 2D‐DIGE and2D‐HPLC combined with MS. Expand
Host cell protein dynamics in recombinant CHO cells
TLDR
Understanding the HCP dynamics will in the future help provide a platform to rationally manipulate and engineer and/or select suitable recombinant CHO cell lines and downstream processing steps to limit problematic HCPs. Expand
A mass spectrometry-based approach to host cell protein identification and its application in a comparability exercise.
TLDR
The workflow was successfully implemented in a comparability exercise assessing HCP populations in drug substance samples before and after a process change, and the results suggest that size can be an important factor in the copurification of HCPs and API. Expand
Profiling the effects of process changes on residual host cell proteins in biotherapeutics by mass spectrometry
TLDR
An advanced liquid chromatography/mass spectrometry platform was used to identify and quantify residual Escherichia coli host cell proteins (HCPs) in the drug substance (DS) of several peptibodies, demonstrating that HCPs that carry through purification processes to be detectable in DS are not always among those that are the most abundant upstream. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 45 REFERENCES
Host cell contaminant protein assay development for recombinant biopharmaceuticals.
  • L. Eaton
  • Chemistry, Medicine
  • Journal of chromatography. A
  • 1995
TLDR
An HCP immunoassay may be thought of as a necessary quantitative tool for the optimization and validation of biopharmaceutical purification process efficiency and consistency, rather than as an end in itself. Expand
Analysis for residual host cell proteins and DNA in process streams of a recombinant protein product expressed in Escherichia coli cells.
TLDR
The study described herein will describe the technical rationale for measuring the clearance of HCP and DNA in the entire bioprocessing to purification from an Escherichia coli-derived expression system and the development of three robust methods that provide the essential process data needed. Expand
Demonstration of Robust Host Cell Protein Clearance in Biopharmaceutical Downstream Processes
TLDR
The demonstration of robust HCP clearance through this comprehensive strategy can potentially be used to eliminate the need for routine analytical testing or for establishing acceptance criteria for these impurities as well as to demonstrate robust operation of the entire downstream purification process. Expand
Proteomic studies support the use of multi‐product immunoassays to monitor host cell protein impurities
TLDR
A comparative proteomics study of three independently generated CHO cell lines was performed and results suggest that multi‐product immunoassays are suitable for monitoring host cell proteins in biopharmaceuticals produced in different CHO cell Lines. Expand
Development of a quantitative assay for residual host cell proteins in a recombinant subunit vaccine against human respiratory syncytial virus.
TLDR
A process-specific immunoligand assay based on the Threshold system for the quantification of residual host cell proteins (HCPs) in a recombinant subunit vaccine candidate against the human respiratory syncytial virus is developed and validated, becoming the first sensitive HCP assay reported for a vaccine. Expand
A quantitative slot blot assay for host cell protein impurities in recombinant proteins expressed in E. coli.
TLDR
A novel means of host cell protein quantitation is described, in which a slot blot system was employed together with scanning laser densitometry to allow picogram level sensitivity in detection of residual host cell proteins in unpurified fermentation products and final purified bulk samples. Expand
Measurement of cytokines by bioassays: theory and application.
TLDR
This review addresses the practical and statistical considerations for the development of valid bioassays, the preparation and use of WHO IS and RR and, in brief, the types of bioassay methods applicable to potency measurements of individual cytokines. Expand
Identification of cellular changes associated with increased production of human growth hormone in a recombinant Chinese hamster ovary cell line
A proteomics approach was used to identify the proteins potentially implicated in the cellular response concomitant with elevated production levels of human growth hormone in a recombinant ChineseExpand
Comparative proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate.
TLDR
Data reveal both the adaptive responses and molecular mechanisms enabling mammalian cells in culture to achieve high-level recombinant monoclonal antibody production. Expand
Host cell protein clearance during protein a chromatography: Development of an improved column wash step
TLDR
A significant mechanistic finding presented in this work is that HCP contaminants that persist following Protein A capture predominantly comprise species that associate with the product in preference to direct interaction with the chromatographic resin, suggesting that the development of improved column wash techniques to maximize HCP clearance ought to focus on disrupting protein–HCP interactions rather than Protein A–H CP interactions. Expand
...
1
2
3
4
5
...