Host cell protein analysis in therapeutic protein bioprocessing - methods and applications

Biotechnology Journal

Volumn 8, Issue 6, 2013, Pages 655-670

  Tscheliessnig, Anne Luise ^a   Konrath, Julita ^a,d   Bates, Ron ^b   Jungbauer, Alois ^a,c  

^a UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES   (Austria)

^b Austrian Centre of Industrial Biotechnology ^*

^c AUSTRIAN CENTRE OF INDUSTRIAL BIOTECHNOLOGY   (Austria)

^d Baxter Life Science   (Austria)

Author keywords

Chinese hamster ovary (CHO) cells; ELISA; Escherichia coli; Host cell protein (HCP); Two dimensional difference gel electrophoresis (2D DIGE)

Indexed keywords

2D DIGE; BIOPROCESS DEVELOPMENT; CHINESE HAMSTER OVARY CELLS; ELISA; FERMENTATION CONDITIONS; HOST CELL PROTEIN; QUALITATIVE INFORMATION; THERAPEUTIC PROTEIN;

CELL CULTURE; CELLS; ELECTROPHORESIS; ESCHERICHIA COLI;

PROTEINS;

ANTIBODY; DISULFIDE; DITHIOTHREITOL; DODECYL SULFATE SODIUM; INTERLEUKIN 2; RECOMBINANT PROTEIN; STAPHYLOCOCCUS PROTEIN A;

BIOSENSOR; CELL CULTURE; CELL LINE; CELL LYSATE; CHO CELL; DOWNSTREAM PROCESSING; ENZYME LINKED IMMUNOSORBENT ASSAY; ESCHERICHIA COLI; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HOST CELL; HUMAN; HYDROPHOBIC INTERACTION CHROMATOGRAPHY; HYDROPHOBICITY; IMMUNOBLOTTING; ION EXCHANGE CHROMATOGRAPHY; LIMIT OF DETECTION; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MOLECULAR WEIGHT; PATIENT SAFETY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN GLYCOSYLATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PURIFICATION; REVIEW; SURFACE ENHANCED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; TWO DIMENSIONAL DIFFERENCE GEL ELECTROPHORESIS; TWO DIMENSIONAL GEL ELECTROPHORESIS; WESTERN BLOTTING;

ANIMALS; ANTIBODIES, MONOCLONAL; BACTERIAL PROTEINS; BIOLOGICAL PRODUCTS; BIOTECHNOLOGY; CHO CELLS; CRICETINAE; CRICETULUS; ESCHERICHIA COLI; RECOMBINANT PROTEINS; TWO-DIMENSIONAL DIFFERENCE GEL ELECTROPHORESIS;

CRICETULUS GRISEUS; ESCHERICHIA COLI;

EID: 84878989389     PISSN: 18606768     EISSN: 18607314     Source Type: Journal    
DOI: 10.1002/biot.201200018     Document Type: Review

References (78)

1. Simmerman, H., Donnelly, R. P., Defining your product profile and maintaining control over it. BioProcess Int. 2005, 3, 32-40.
2. Q6B, I., International Conference on Harmonisation; Draft guidance on specifications: Test procedures and acceptance criteria for biotechnological/biological products-FDA. Notice. Fed. Regist. 1998, 63, 31506-31513.
3. Garg, A., Solas, D. W., Takahashi, L. H., Cassella, J. V., Forced degradation of fentanyl: Identification and analysis of impurities and degradants. J. Pharm. Biomed. Anal. 2010, 53, 325-334.
4. Mehta, S., Shah, R. P., Priyadarshi, R., Singh, S., LC and LC-MS/TOF studies on stress degradation behaviour of candesartan cilexetil. J. Pharm. Biomed. Anal. 2010, 52, 345-354.
5. Pan, C., Liu, F., Motto, M., Identification of pharmaceutical impurities in formulated dosage forms. J. Pharm. Sci. 2010, 100, 1228-1259.
6. Raijada, D. K., Prasad, B., Paudel, A., Shah, R. P., Singh, S., Characterization of degradation products of amorphous and polymorphic forms of clopidogrel bisulphate under solid state stress conditions. J. Pharm. Biomed. Anal. 2010, 52, 332-344.
7. Debrauwer, L., Zalko, D., Bories, G., Tulliez, J., Electrospray ionization mass spectrometric study of N-oxidation products of clenbuterol. Rapid Commun. Mass Spectrom. 1997, 11, 1089-1094.
8. Walsh, G., Post-translational modifications of protein biopharmaceuticals. Drug Discovery Today 2010, 15, 773-780.
9. Singh, S., Handa, T., Narayanam, M., Sahu, A. et al., A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products. J. Pharm. Biomed. Anal. 2012, 69, 148-173.
10. Gao, S. X., Zhang, Y., Stansberry-Perkins, K., Buko, A. et al., Fragmentation of a highly purified monoclonal antibody attributed to residual CHO cell protease activity. Biotechnol. Bioeng. 2011, 108, 977-982.
11. Carter-Franklin, J. N., Victa, C., McDonald, P., Fahrner, R., Fragments of protein A eluted during protein A affinity chromatography. J. Chromatogr. A. 2007, 1163, 105-111.
12. Follman, D. K., Fahrner, R. L., Factorial screening of antibody purification processes using three chromatography steps without protein A. J. Chromatogr. A. 2004, 1024, 79-85.
13. Jungbauer, A., Boschetti, E., Manufacture of recombinant proteins with safe and validated chromatographic sorbents. J. Chromatogr., B: Biomed. Sci. Appl. 1994, 662, 143-179.
14. Pan, C., Harmon, F., Toscano, K., Liu, F., Vivilecchia, R., Strategy for identification of leachables in packaged pharmaceutical liquid formulations. J. Pharm. Biomed. Anal. 2008, 46, 520-527.
15. Jin, M., Szapiel, N., Zhang, J., Hickey, J., Ghose, S., Profiling of host cell proteins by two-dimensional difference gel electrophoresis (2D-DIGE): Implications for downstream process development. Biotechnol. Bioeng. 2009, 105, 306-316.
16. Bartlow, P., Uechi, G. T., Cardamone, J. J. Jr., Sultana, T. et al., Identification of native Escherichia coli BL21 (DE3) proteins that bind to immobilized metal affinity chromatography under high imidazole conditions and use of 2D-DIGE to evaluate contamination pools with respect to recombinant protein expression level. Protein Expression Purif. 2011, 78, 216-224.
17. Grzeskowiak, J. K., Tscheliessnig, A., Toh, P. C., Chusainow, J. et al., 2-D DIGE to expedite downstream process development for human monoclonal antibody purification. Protein Expression Purif. 2009, 66, 58-65.
18. Grzeskowiak, J. K., Tscheliessnig, A., Toh, P. C., Chusainow, J. et al., Two-dimensional fluorescence difference gel electrophoresis for comparison of affinity and non-affinity based downstream processing of recombinant monoclonal antibody. J. Chromatogr. A. 2009, 1216, 4902-4912.
19. Clark, K. J. R., Chaplin, F. W. R., Harcum, S. W., Temperature effects on product-quality-related enzymes in batch CHO cell cultures producing recombinant tPA. Biotechnol. Prog. 2004, 20, 1888-1892.
20. Wang, X., Hunter, A. K., Mozier, N. M., Host cell proteins in biologics development: Identification, quantitation and risk assessment. Biotechnol. Bioeng. 2009, 103, 446-458.
21. Godovac-Zimmermann, J., Brown, L. R., Perspectives for mass spectrumetry and functional proteomics. Mass Spectrom. Rev. 2001, 20, 1-57.
22. Shukla, A. A., Jiang, C., Ma, J., Rubacha, M. et al., Demonstration of robust host cell protein clearance in biopharmaceutical downstream processes. Biotechnol. Prog. 2008, 24, 615-622.
23. Champion, K., Madden, H., Dougherty, J., Shacter, E., Defining your product profile and maintaining control over it, part 2. BioProcess Int. 2005, 3, 52-57.
24. Pezzini, J., Joucla, G., Gantier, R., Toueille, M. et al., Antibody capture by mixed-mode chromatography: A comprehensive study from determination of optimal purification conditions to identification of contaminating host cell proteins. J. Chromatogr. A. 2011, 1218, 8197-8208.
25. Zhu, D., Saul, A. J., Miles, A. P., A quantitative slot blot assay for host cell protein impurities in recombinant proteins expressed in E. coli. J. Immunol. Methods 2005, 306, 40-50.
26. Savino, E., Hu, B., Sellers, J., Sobjak, A. et al., Development of an in-house, process-specific ELISA for detecting HCP in a therapeutic antibody, Part 2. BioProcess Int. 2011, 9, 68-75.
27. Briggs, J., Panfili, P. R., Quantitation of DNA and protein impurities in biopharmaceuticals. Anal. Chem. 1991, 63, 850-859.
28. Fortis, F. D., Guerrier, L., Areces, L. B., Antonioli, P. et al., A new approach for the detection and identification of protein impurities using combinatorial solid phase ligand libraries. J. Proteome Res. 2006, 5, 2577-2585.
29. Doneanu, C., Xenopoulos, A., Fadgen, K., Murphy, J. et al., Analysis of host-cell proteins in biotherapeutic proteins by comprehensive online two-dimensional liquid chromatography/mass spectrometry. mAbs 2012, 4, 24-44.
30. Liu, N., Brevnov, M., Furtado, M., Liu, J., Host cellular protein quantification: Using an automated solid-phase proximity ligation assay. BioProcess Int. 2012, 10, 44-50.
31. Teeparuksapun, K., Hedström, M., Kanatharana, P., Thavarungkul, P., Mattiasson, B., Capacitive immunosensor for the detection of host cell proteins. J. Biotechnol. 2010, 157, 207-213.
32. Sisodiya, V. N., Lequieu, J., Rodriguez, M., McDonald, P., Lazzareschi, K. P., Studying host cell protein interactions with monoclonal antibodies using high throughput protein A chromatography. Biotechnol. J. 2012, 7, 1233-1241.
33. Savino, E., Hu, B., Sellers, J., Sobjak, A. et al., Development of an in-house, process-specific ELISA for detecting HCP in a therapeutic antibody, part 1. BioProcess Int. 2011, 9, 38-47.
34. Wan, M., Wang, Y., Rabideau, S., Moreadith, R. et al., An enzyme-linked immunosorbent assay for host cell protein contaminants in recombinant PEGylated staphylokinase mutant SY161. J. Pharm. Biomed. Anal. 2002, 28, 953-963.
35. Whitmire, M. L., Eaton, L. C., An immunoligand assay for quantitation of process specific Escherichia coli host cell contaminant proteins in a recombinant bovine somatotropin. J. Immunoassay 1997, 18, 49-65.
36. Flatman, S., Alam, I., Gerard, J., Mussa, N., Process analytics for purification of monoclonal antibodies. J. Chromatogr. B. 2007, 848, 79-87.
37. Eaton, L. C., Host cell contaminant protein assay development for recombinant biopharmaceuticals. J. Chromatogr. A. 1995, 705, 105-114.
38. Champion, K. M., Nishihara, J. C., Aldor, I. S., Moreno, G. T. et al., Comparison of the Escherichia coli proteomes for recombinant human growth hormone producing and nonproducing fermentations. Proteomics 2003, 3, 1365-1373.
39. Krawitz, D. C., Forrest, W., Moreno, G. T., Kittleson, J., Champion, K. M., Proteomic studies support the use of multi-product immunoassays to monitor host cell protein impurities. Proteomics 2006, 6, 94-110.
40. Schwertner, D., Kirchner, M., Are generic HCP assays outdated? BioProcess Int. 2012, 8, 56-62.
41. Wang, X., Schomogy, T., Wells, K., Mozier, N. M., Improved HCP quantitation by minimizing antibody cross-reactivity to target proteins. BioProcess Int. 2010, 8, 18-24.
42. Dagouassat, N., Haeuw, J.-F. O., Robillard, V., Damien, F. et al., Development of a quantitative assay for residual host cell proteins in a recombinant subunit vaccine against human respiratory syncytial virus. J. Immunol. Methods 2001, 251, 151-159.
43. Mattiasson, B., Teeparuksapun, K., Hedström, M., Immunochemical binding assays for detection and quantification of trace impurities in biotechnological production. Trends Biotechnol. 2009, 28, 20-27.
44. Aldor, I. S., Krawitz, D. C., Forrest, W., Chen, C. et al., Proteomic profiling of recombinant Escherichia coli in high-cell-density fermentations for improved production of an antibody fragment biopharmaceutical. Appl. Environ. Microbiol. 2005, 71, 1717-1728.
45. Grzeskowiak, J. K., Tscheliessnig, A., Wu, M. W., Toh, P. C. et al., Two-dimensional difference fluorescence gel electrophoresis to verify the scale-up of a non-affinity-based downstream process for isolation of a therapeutic recombinant antibody. Electrophoresis 2010, 31, 1862-1872.
46. Ramasawmy, R., Cunha-Neto, E., Fae, K., Martello, F. et al., The monocyte chemoattractant protein-1 gene polymorphism is associated with cardiomyopathy in human chagas disease. Clin. Infect. Dis. 2006, 43, 305-311.
47. Görg, A., Advances in 2D gel techniques. Trends Biotechnol. 2000, 18, 3-6.
48. Berrill, A., Ho, S. V., Bracewell, D. G., Product and contaminant measurement in bioprocess development by SELDI-MS. Biotechnol. Prog. 2010, 26, 881-887.
49. Valente, K. N., Choe, L. H., Lenhoff, A. M., Lee, K. H., Optimization of protein sample preparation for two-dimensional electrophoresis. Electrophoresis 2012, 33, 1947-1957.
50. Nishihara, J. C., Champion, K. M., Quantitative evaluation of proteins in one- and two-dimensional polyacrylamide gels using a fluorescent stain. Electrophoresis 2002, 23, 2203-2215.
51. Marouga, R., David, S., Hawkins, E., The development of the DIGE system: 2D fluorescence difference gel analysis technology. Anal. Bioanal. Chem. 2005, 382, 669-678.
52. Alban, A., David, S. O., Bjorkesten, L., Andersson, C. et al., A novel experimental design for comparative two-dimensional gel analysis: Two-dimensional difference gel electrophoresis incorporating a pooled internal standard. Proteomics 2003, 3, 36-44.
53. Chevalier, F., Highlights on the capacities of 'Gel-based' proteomics. Proteome Sci. 2010, 8, 23.
54. Hrebicek, T., Dürrschmid, K., Auer, N., Bayer, K., Rizzi, A., Effect of CyDye minimum labeling in differential gel electrophoresis on the reliability of protein identification. Electrophoresis 2007, 28, 1161-1169.
55. Rabilloud, T., Chevallet, M., Luche, S., Lelong, C., Two-dimensional gel electrophoresis in proteomics: Past, present and future. J. Proteomics 2010, 73, 2064-2077.
56. Spandidos, A., Rabbitts, T. H., Sub-proteome differential display: Single gel comparison by 2D electrophoresis and mass spectrometry. J. Mol. Biol. 2002, 318, 21-31.
57. Stansfield, S. H., Allen, E. E., Dinnis, D. M., Racher, A. J. et al., Dynamic analysis of GS-NS0 cells producing a recombinant monoclonal antibody during fed-batch culture. Biotechnol. Bioeng. 2007, 97, 410-424.
58. Kumar, N., Maurya, P., Gammell, P., Dowling, P. et al., Proteomic profiling of secreted proteins from CHO cells using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. Biotechnol. Prog. 2008, 24, 273-278.
59. Ashe, M. P., Bill, R. M., Mapping the yeast host cell response to recombinant membrane protein production: Relieving the biological bottlenecks. Biotechnol. J. 2011, 6, 707-714.
60. Goncalves, G. A. L., Bower, D. M., Prazeres, D. M. F., Monteiro, G. A., Prather, K. L. J., Rational engineering of Escherichia coli strains for plasmid biopharmaceutical manufacturing. Biotechnol. J. 2012, 7, 251-261.
61. Dietmair, S., Nielsen, L. K., Timmins, N. E., Mammalian cells as biopharmaceutical production hosts in the age of omics. Biotechnol. J. 2012, 7, 75-89.
62. Tait, A. S., Hogwood, C. E. M., Smales, C. M., Bracewell, D. G., Host cell protein dynamics in the supernatant of a mAb producing CHO cell line. Biotechnol. Bioeng. 2012, 109, 971-982.
63. Smales, C. M., Dinnis, D. M., Stansfield, S. H., Alete, D. et al., Comparative proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate. Biotechnol. Bioeng. 2004, 88, 474-488.
64. Dinnis, D. M., Stansfield, S. H., Schlatter, S., Smales, C. M. et al., Functional proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate. Biotechnol. Bioeng. 2006, 94, 830-841.
65. Pascoe, D. E., Arnott, D., Papoutsakis, E. T., Miller, W. M., Andersen, D. C., Proteome analysis of antibody-producing CHO cell lines with different metabolic profiles. Biotechnol. Bioeng. 2007, 98, 391-410.
66. Underhill, M. F., Smales, C. M., The cold-shock response in mammalian cells: Investigating the HeLa cell cold-shock proteome. Cytotechnology 2007, 53, 47-53.
67. Champion, K. M., Nishihara, J. C., Joly, J. C., Arnott, D., Similarity of the Escherichia coli proteome upon completion of different biopharmaceutical fermentation processes. Proteomics 2001, 1, 1133-1148.
68. Hunter, A. K., Wang, X., Suda, E. J., Herberg, J. T. et al., Separation of product associating E. coli host cell proteins OppA and DppA from recombinant apolipoprotein A-IMilano in an industrial HIC unit operation. Biotechnol. Prog. 2009, 25, 446-453.
69. Carta, G., Jungbauer, A., Protein Chromatography: Process Development and Scale-Up Wiley-VCH, 2010.
70. Shukla, A. A., Hinckley, P., Host cell protein clearance during protein a chromatography: Development of an improved column wash Step. Biotechnol. Prog. 2008, 24, 1115-1121.
71. Nogal, B., Chhiba, K., Emery, J. C., Select host cell proteins coelute with monoclonal antibodies in protein a chromatography. Biotechnol. Prog. 2012, 28, 454-458.
72. Tarrant, R. D. R., Velez-Suberbie, M. L., Tait, A. S., Smales, C. M., Bracewell, D. G., Host cell protein adsorption characteristics during protein a chromatography. Biotechnol. Prog. 2012, 28, 1037-1044.
73. Shukla, A. A., Thömmes, J., Recent advances in large-scale production of monoclonal antibodies and related proteins. Trends Biotechnol. 2010, 28, 253-261.
74. Ferreira, G. M., Dembecki, J., Patel, K., Arunakumari, A., A two-column process to purify antibodies without protein A. BioPharm Int. 2007, 20, 32-43.
75. Xu, B., Lundgren, M., Magnusson, A. C., Fuentes, A., Expression, purification and characterization of the recombinant chimeric IgE Fc-fragment opossum-human-opossum (OSO), an active immunotherapeutic vaccine component. Protein Expression Purif. 2010, 74, 32-41.
76. Rey, G., Wendeler, M. W., Full automation and validation of a flexible ELISA platform for host cell protein and protein A impurity detection in biopharmaceuticals. J. Pharm. Biomed. Anal. 2012, 70, 580-586.
77. Righetti, P. G., Electrophoresis: The march of pennies, the march of dimes. J. Chromatogr. A. 2005, 1079, 24-40.
78. Hayduk, E. J., Choe, L. H., Lee, K. H., A two-dimensional electrophoresis map of Chinese hamster ovary cell proteins based on fluorescence staining. Electrophoresis 2004, 25, 2545-2556.