Analytical aspects of biosimilarity issues of protein drugs

Journal of Pharmaceutical and Biomedical Analysis

Volumn 69, Issue , 2012, Pages 185-195

  Kálmán Szekeres, Zsuzsanna ^a   Olajos, Marcell ^a   Ganzler, Katalin ^a  

^a GEDEON RICHTER LTD   (Hungary)

Author keywords

Biosimilar; Comparability; Immunogenicity; Protein analysis; Protein heterogeneity

Indexed keywords

BIOSIMILAR AGENT; DRUG ADDITIVE; GENETROPIN; HUMAN GROWTH HORMONE; RECOMBINANT ERYTHROPOIETIN; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; SILAPRO; UNCLASSIFIED DRUG;

AMINO ACID ANALYSIS; ANALYTIC METHOD; DRUG ACETYLATION; DRUG IMPURITY; DRUG STABILITY; DRUG STRUCTURE; GLYCOSYLATION; IMMUNOGENICITY; MASS SPECTROMETRY; MYRISTYLATION; PEPTIDE MAPPING; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN METHYLATION; PROTEIN PHOSPHORYLATION; PROTEIN PRENYLATION; PROTEIN QUATERNARY STRUCTURE; PROTEIN SECONDARY STRUCTURE; PROTEIN STRUCTURE; PROTEIN TERTIARY STRUCTURE; REVIEW; SPECTROSCOPY; STRUCTURE ACTIVITY RELATION; UBIQUITINATION; ULTRAVIOLET SPECTROPHOTOMETRY;

ANTIBODIES, MONOCLONAL; BIOLOGICAL AGENTS; BIOTECHNOLOGY; CHROMATOGRAPHY, AFFINITY; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DRUG APPROVAL; EUROPEAN UNION; GLYCOSYLATION; HUMANS; PHARMACEUTICAL PREPARATIONS; POLYSACCHARIDES; PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; THERAPEUTIC EQUIVALENCY; UNITED STATES;

EID: 84865077796     PISSN: 07317085     EISSN: 1873264X     Source Type: Journal    
DOI: 10.1016/j.jpba.2012.04.037     Document Type: Review

References (121)

1. Sheppard A. EGA Biosimilars International Symposium 2011.
2. So A.D., Katz S.L. Biologics Boondoggle. The New York Times 2010.
3. Perry G. 7th EGA Symposium on Biosimilar Medicines 2009.
4. Aradi I. EGA Symposium on Biosimilar Medicines 2011.
5. McCamish M., Woollett G. Worldwide experience with biosimilar development. mAbs 2011, 3:209-217.
6. CHMP, European Medicines Agency, 2011, Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Quality Issues, EMEA/CHMP/BWP/49348/2005, 30th September 2011.
7. Townsend R.R., Basa L.J., Spellman M.W. Identification and characterization of glycopeptides in tryptic maps by high-pH anion-exchange chromatography. Methods in Enzymology 1996, 135-147. Academic Press. W.S.H. Barry, L. Karger (Eds.).
8. Corthals G.L., Aebersold R., Goodlett D.R. Identification of phosphorylation sites using microimmobilized metal affinity chromatography. Methods in Enzymology 2005, 66-81. Academic Press. A.L. Burlingame (Ed.).
9. Smith D.L., Zhou Z. Strategies for locating disulfide bonds in proteins. Methods in Enzymology 1990, 374-389. Academic Press. A.M. James (Ed.).
10. Carr S.A., Annan R.S., Huddleston M.J. Mapping posttranslational modifications of proteins by MS-based selective detection: application to phosphoproteomics. Methods in Enzymology 2005, 82-115. Academic Press. A.L. Burlingame (Ed.).
11. Hogg P.J. Disulfide bonds as switches for protein function. Trends Biochem. Sci. 2003, 28:210-214.
12. Zhao X., Pan F., Cowsill B., Lu J.R., Garcia-Gancedo L., Flewitt A.J., Ashley G.M., Luo J. Interfacial immobilization of monoclonal antibody and detection of human prostate-specific antigen. Langmuir 2011, 27:7654-7662.
13. Schiestl M. EMEA Workshop on Biosimilar Monoclonal Antibodies 2009.
14. Haris P.I., Severcan F. FTIR spectroscopic characterization of protein structure in aqueous and non-aqueous media. J. Mol. Catal. B: Enzym. 1999, 7:207-221.
15. Kox S. IGPA 2011 Conference 2011.
16. Farley A.R., Link A.J. Chapter 40 Identification and quantification of protein posttranslational modifications. Methods in Enzymology 2009, 725-763. Academic Press. R.B. Richard, P.D. Murray (Eds.).
17. CBER, CDER, U.S. Food and Drug Administration (FDA), 1996, Demonstration of Comparability of Human Biological Products, Including Therapeutic Biotechnology-derived Products, April 1996.
18. CHMP, European Medicines Agency, London, 2009, Concept Paper on the Development of a Guideline on Similar Biological Medicinal Products Containing Monoclonal Antibodies.
19. Streicher W.W., Lopez M.M., Makhatadze G.I. Modulation of quaternary structure of S100 proteins by calcium ions. Biophys. Chem. 2010, 151:181-186.
20. Staub A., Guillarme D., Schappler J., Veuthey J.-L., Rudaz S. Intact protein analysis in the biopharmaceutical field. J. Pharm. Biomed. Anal. 2011, 55:810-822.
21. Lundblad R.L. Approaches to the Conformational Analysis of Biopharmaceuticals 2009, Chapman and Hall/CRC.
22. Bax A. Two-dimensional NMR and protein structure. Annu. Rev. Biochem. 1989, 58:223-256.
23. Handbook of Pharmaceutical Biotechnology 2006, John Wiley & Sons, Inc.
24. Yates J.R., Speicher S., Griffin P.R., Hunkapiller T. Peptide mass maps: a highly informative approach to protein identification. Anal. Biochem. 1993, 214:397-408.
25. Steen H., Mann M. The abc's (and xyz's) of peptide sequencing. Nat. Rev. Mol. Cell Biol. 2004, 5:699-711.
26. Edman P. Method for determination of the amino acid sequence in peptides. Acta Chem. Scand. 1950, 4:283-293.
27. Aschermann K., Lutter P., Wattenberg A. Current status of protein quantification technologies. Bioprocess Int. 2008, 6:44-53.
28. Feige M.J., Hagn F., Esser J., Kessler H., Buchner J. Influence of the internal disulfide bridge on the folding pathway of the CL antibody domain. J. Mol. Biol. 2007, 365:1232-1244.
29. Wedemeyer W.J., Welker E., Narayan M., Scheraga H.A. Disulfide bonds and protein folding. Biochemistry 2000, 39:4207-4216.
30. Almagro J.C., Raghunathan G., Beil E., Janecki D.J., Chen Q., Dinh T., LaCombe A., Connor J., Ware M., Kim P.H., Swanson R.V., Fransson J. Characterization of a high-affinity human antibody with a disulfide bridge in the third complementarity-determining region of the heavy chain. J. Mol. Recognit. 2012, 25:125-135.
31. Bagal D., Valliere-Douglass J.F., Balland A., Schnier P.D. Resolving disulfide structural isoforms of IgG2 monoclonal antibodies by ion mobility mass spectrometry. Anal. Chem. 2010, 82:6751-6755.
32. Hawe A., Sutter M., Jiskoot W. Extrinsic fluorescent dyes as tools for protein characterization. Pharm. Res. 2008, 25:1487-1499.
33. Poole R.A., Hawe A., Jiskoot W., Braeckmans K. Fluorescence spectroscopy to characterize protein aggregates and particles. Analysis of Aggregates and Particles in Protein Pharmaceuticals 2012, John Wiley & Sons, Inc., pp. 201-226.
34. Manjasetty B.A., Turnbull A.P., Panjikar S., Büssow K., Chance M.R. Automated technologies and novel techniques to accelerate protein crystallography for structural genomics. Proteomics 2008, 8:612-625.
35. Kozlowski S., Woodcock J., Midthun K., Behrman Sherman R. Developing the Nation's Biosimilars Program. N. Eng. J. Med. 2011, 365:385-388.
36. CBER, CDER, U.S. Food and Drug Administration (FDA), 1999, Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products.
37. Aitken A., Learmonth M.P. Protein determination by UV absorption the protein protocols handbook 2002, 3-6. Humana Press. J.M. Walker (Ed.).
38. Bradford M.M. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72:248-254.
39. Lowry O.H., Farr N.J., Randall R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 1951, 193:265-275.
40. Smith P.K., Krohn R.I., Hermanson G.T., Mallia A.K., Gartner F.H., Provenzano M.D., Fujimoto E.K., Goeke N.M., Olson B.J., Klenk D.C. Measurement of protein using bicinchoninic acid. Anal. Biochem. 1985, 150:76-85.
41. Schellekens H. Biosimilar therapeutics-what do we need to consider?. Clin. Kidney J. 2008, 2:27-36.
42. Skrlin A., Krnic E.K., Gosak D., Prester B., Mrsa V., Vuletic M., Runac D. Correlation of liquid chromatographic and biological assay for potency assessment of filgrastim and related impurities. J. Pharm. Biomed. Anal. 2010, 53:262-268.
43. Park S.S., Park J., Ko J., Chen L., Meriage D., Crouse-Zeineddini J., Wong W., Kerwin B.A. Biochemical assessment of erythropoietin products from Asia versus US Epoetin alfa manufactured by Amgen. J. Pharm. Sci. 2009, 98:1688-1699.
44. Combe C., Tredree R.L., Schellekens H. Biosimilar epoetins: an analysis based on recently implemented European medicines evaluation agency guidelines on comparability of biopharmaceutical proteins. Pharmacotherapy 2005, 25:954-962.
45. Meager A., Dolman C., Dilger P., Bird C., Giovannoni G., Schellekens H., Thorpe R., Wadhwa M. An assessment of biological potency and molecular characteristics of different innovator and noninnovator interferon-beta products. J. Interferon Cytokine Res. 2011, 31:383-392.
46. Brockmeyer C., Seidl A. Binocrit: assessment of quality, safety and efficacy of biopharmaceuticals. Eur. J. Hosp. Pharm. Practice 2009, 15:34-40.
47. Schellekens H. Biosimilar epoetins: how similar are they?. Eur. J. Hosp. Pharm. 2004, 3:43-47.
48. Skrlin A., Radic I., Vuletic M., Schwinke D., Runac D., Kusalic T., Paskvan I., Krsic M., Bratos M., Marinc S. Comparison of the physicochemical properties of a biosimilar filgrastim with those of reference filgrastim. Biologicals 2010, 38:557-566.
49. Sörgel F., Lerch H., Lauber T. Physicochemical and biologic comparability of a biosimilar granulocyte colony-stimulating factor with its reference product. BioDrugs 2010, 24:347-357.
50. Doyle H.A., Mamula M.J. Post-translational protein modifications in antigen recognition and autoimmunity. Trends Immunol. 2001, 22:443-449.
51. Meadows L., Wang W., den Haan J.M.M., Blokland E., Reinhardus C., Drijfhout J.W., Shabanowitz J., Pierce R., Agulnik A.I., Bishop C.E., Hunt D.F., Goulmy E., Engelhard V.H. The HLA-A*0201-restricted H-Y antigen contains a posttranslationally modified cysteine that significantly affects T cell recognition. Immunity 1997, 6:273-281.
52. Arnold J.N., Wormald M.R., Sim R.B., Rudd P.M., Dwek R.A. The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu. Rev. Immunol. 2007, 25:21-50.
53. Wadhwa M., Thorpe R. The challenges of immunogenicity in developing biosimilar products. IDrugs 2009, 12:440-444.
54. Porter S. Human immune response to recombinant human proteins. J. Pharm. Sci. 2001, 90:1-11.
55. Hendrickson Jeanne E., Desmarets M., Deshpande Seema S., Chadwick T.E., Hillyer Christopher D., Roback John D., Zimring James C. Recipient inflammation affects the frequency and magnitude of immunization to transfused red blood cells. Transfusion (Paris) 2006, 46:1526-1536.
56. Ross C., Clemmesen K.M., Svenson M., Sörensen P.S., Koch-Henriksen N., Skovgaard G.L., Bendtzen K. Immunogenicity of interferon-beta in multiple sclerosis patients: influence of preparation, dosage, dose frequency, and route of administration. Danish Multiple Sclerosis Study Group. Ann. Neurol. 2000, 48:706-712.
57. Hermeling S., Crommelin D., Schellekens H., Jiskoot W. Structure-immunogenicity relationships of therapeutic proteins. Pharm. Res. 2004, 21:897-903.
58. Schellekens H. The immunogenicity of therapeutic proteins. Discov. Med. 2010, 9:560-564.
59. Mikulskis A., Yeung D., Subramanyam M., Amaravadi L., Solution ELISA as a platform of choice for development of robust, drug tolerant immunogenicity assays in support of drug development. J. Immunol. Methods 2011, 365:38-49.
60. Putnam W.S., Prabhu S., Zheng Y., Subramanyam M., Wang Y.-M.C. Pharmacokinetic, pharmacodynamic and immunogenicity comparability assessment strategies for monoclonal antibodies. Trends Biotechnol. 2010, 28:509-516.
61. Koren E., Smith H.W., Shores E., Shankar G., Finco-Kent D., Rup B., Barrett Y.-C., Devanarayan V., Gorovits B., Gupta S., Parish T., Quarmby V., Moxness M., Swanson S.J., Taniguchi G., Zuckerman L.A., Stebbins C.C., Mire-Sluis A. Recommendations on risk-based strategies for detection and characterization of antibodies against biotechnology products. J. Immunol. Methods 2008, 333:1-9.
62. Gupta S., Indelicato S.R., Jethwa V., Kawabata T., Kelley M., Mire-Sluis A.R., Richards S.M., Rup B., Shores E., Swanson S.J., Wakshull E. Recommendations for the design, optimization, and qualification of cell-based assays used for the detection of neutralizing antibody responses elicited to biological therapeutics. J. Immunol. Methods 2007, 21:1-18.
63. De Groot A.S., McMurry J., Moise L. Prediction of immunogenicity: in silico paradigms, ex vivo and in vivo correlates. Curr. Opin. Pharmacol. 2008, 8:620-626.
64. Harding F.A., Stickler M.M., Razo J., DuBridge R. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. mAbs 2010, 2:256-265.
65. Koren E., De Groot A.S., Jawa V., Beck K.D., Boone T., Rivera D., Li L., Mytych D., Koscec M., Weeraratne D., Swanson S., Martin W. Clinical validation of the in silico prediction of immunogenicity of a human recombinant therapeutic protein. Clin. Immunol. 2007, 124:26-32.
66. Bryson C.J., Jones T.D., Baker M.P. Prediction of immunogenicity of therapeutic proteins: validity of computational tools. BioDrugs 2010, 24:1-8.
67. Beers M.M.C., Sauerborn M., Gilli F., Brinks V., Schellekens H., Jiskoot W. Oxidized and aggregated recombinant human interferon beta is immunogenic in human interferon beta transgenic mice. Pharm. Res. 2011, 28:2393-2402.
68. Jaber A., Driebergen R., Giovannoni G., Schellekens H., Simsarian J., Antonelli M. The Rebif(R) new formulation story: it's not trials and error. Drugs R&D 2007, 8:335-348.
69. Gowthaman U., Agrewala J.N. In silico methods for predicting T-cell epitopes: Dr Jekyll or Mr Hyde?. Expert Rev. Proteomics 2009, 6:527-537.
70. Rosenberg A.S. Effects of protein aggregates: an immunologic perspective. AAPS J. 2006, 8:E501-E507.
71. Casadevall N., Nataf J., Viron B., Kolta A., Kiladjian J.-J., Martin-Dupont P., Michaud P., Papo T., Ugo V., Teyssandier I., Varet B., Mayeux P. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N. Eng. J. Med. 2002, 346:469-475.
72. Gershon S.K., Luksenburg H., Coté T.R., Braun M.M. Pure red-cell aplasia and recombinant erythropoietin. N. Eng. J. Med. 2002, 346:1584-1586.
73. Boven K., Knight J., Bader F., Rossert J., Eckardt K.-U., Casadevall N. Epoetin-associated pure red cell aplasia in patients with chronic kidney disease: solving the mystery. Nephrol. Dial. Transplant. 2005, 20:iii33-iii40.
74. Schellekens H. Relationship between biopharmaceutical immunogenicity of epoetin alfa and pure red cell aplasia. Curr. Med. Res. Opin. 2003, 19:433-434.
75. Epogen. Full Prescribing Information 2012, Amgen, Thousand Oaks, CA, 6th January 2012.
76. Procrit. Full Prescribing Information 2012, OrthoBiotechProducts, 6th January 2012.
77. Schellekens H. How to predict and prevent the immunogenicity of therapeutic proteins. Biotechnol. Ann. Rev. 2008, 191-202. Elsevier. M.R. El-Gewely (Ed.).
78. Macdougall I.C. Antibody-mediated pure red cell aplasia (PRCA): epidemiology, immunogenicity and risks. Nephrol. Dial. Transplant. 2005, 20:iv9-iv15.
79. A. Breckenridge, MHRA, 2010, Eprex® (Epoetin Alfa) and pure red cell aplasia-contraindication of subcutaneous administration to patients with chronic renal disease.
80. CHMP, European Medicines Agency, London, 2006, Questions and Ansvers on Recommendation for Refusal of Marketing Application for Alferon, EMEA/190896/2006.
81. Haag-Weber M., Vetter A., Thyroff-Friesinger U., Group I.-S. Therapeutic equivalence, long-term efficacy and safety of HX575 in the treatment of anemia in chronic renal failure patients receiving hemodialysis. Clin. Nephrol. 2009, 72:380-390.
82. Berghout A. Clinical programs in the development of similar biotherapeutic products: rationale and general principles. Biologicals 2011, 39:293-296.
83. EMEA, 2006, Omnitrope: scientific discussion, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000607/WC500043692.pdf.
84. Neupogen. Full prescribing information 2009, Amgen, 6th January 2012, http://pi.amgen.com/united_states/neupogen/neupogen_pi_hcp_english.pdf.
85. Praditpornsilpa K., Tiranathanagul K., Kupatawintu P., Jootar S., Intragumtornchai T., Tungsanga K., Teerapornlertratt T., Lumlertkul D., Townamchai N., Susantitaphong P., Katavetin P., Kanjanabuch T., Avihingsanon Y., Eiam-Ong S. Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies. Kidney Int. 2011, 80:88-92.
86. Windisch J. FDA Public Hearing: Approval Pathway for Biosimilar and Interchangeable Biological Products Comments by the European Generic medicines Association (EGA) 2010, FDA White Oak Campus.
87. CDER, CBER, U.S. Food and Drug Administration (FDA), Rockville, MD, USA, 2012, Biosimilars: Questions and Ansvers Regarding Implementation of the Biologics Price Competition Innovation Act of 2009, pp. 15.
88. Jeong J.-S., Lim H.-M., Kim S.-K., Ku H.-K., Oh K.-H., Park S.-R. Quantification of human growth hormone by amino acid composition analysis using isotope dilution liquid-chromatography tandem mass spectrometry. J. Chromatogr. A 2011, 1218:6596-6602.
89. Gallagher S.R. One-dimensional SDS gel electrophoresis of proteins. Current Protocols in Protein Science 2001, John Wiley & Sons, Inc.
90. Laue T.M., Stafford Iii W.F. Modern applications of analytical ultracentrifugation. Annu. Rev. Biophys. Biomol. Struct. 1999, 28:75-100.
91. Noble J.E., Bailey M.J.A. Chapter 8 quantitation of protein. Methods in Enzymology 2009, 73-95. Academic Press. R.B. Richard, P.D. Murray (Eds.).
92. Konermann L., Tong X., Pan Y. Protein structure and dynamics studied by mass spectrometry: H/D exchange, hydroxyl radical labeling, and related approaches. J. Mass Spectrometry 2008, 3:1021-1036.
93. Thiede B., Höhenwarter W., Krah A., Mattow J., Schmid M., Schmidt F., Jungblut P.R. Peptide mass fingerprinting. Methods 2005, 35:237-247.
94. Zhu Z., Lu J.J., Liu S. Protein separation by capillary gel electrophoresis: a review. Anal. Chim. Acta 2012, 709:21-31.
95. Cohen A.S., Smisek D.L., Keohavong P. Capillary gel electrophoresis of biopolymers. TrAC Trends Anal. Chem. 1993, 12:195-202.
96. Righetti P.G., Fasoli E., Righetti S.C. Conventional isoelectric focusing in gel slabs and capillaries and immobilized pH gradients. Protein Purification 2011, John Wiley & Sons, Inc., pp. 379-409.
97. Görg A., Obermaier C., Boguth G., Harder A., Scheibe B., Wildgruber R., Weiss W. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 2000, 21:1037-1053.
98. Llop E., Gallego R.G., Belalcazar V., Gerwig G.J., Kamerling J.P., Segura J., Pascual J.A. Evaluation of protein N-glycosylation in 2-DE: erythropoietin as a study case. Proteomics 2007, 7:4278-4291.
99. Thormann W. Capillary electrophoretic separations. Methods Biochem. Anal. 2011, 54:451-485.
100. Nikolin B., Imamovic B., Medanhodzic-Vuk S., Sober M. High performance liquid chromatography in pharmaceutical analyses. Bosn. J. Basic Med. Sci. 2004, 4:5-9.
101. Edelmann M.J. Strong cation exchange chromatography in analysis of posttranslational modifications: innovations and perspectives. J. Biomed. Biotechnol. 2011, 2011.
102. Cutler P. Size-exclusion chromatography. Methods Mol. Biol. 1996, 59:255-267.
103. Alpert A.J. Hydrophilic-interaction chromatography for the separation of peptides, nucleic acids and other polar compounds. J. Chromatogr. A 1990, 499:177-196.
104. Buszewski B., Noga S. Hydrophilic interaction liquid chromatography (HILIC)-a powerful separation technique. Anal. Bioanalyt. Chem. 2012, 402:231-247.
105. Fausnaugh J.L., Kennedy L.A., Regnier F.E. Comparison of hydrophobic-interaction and reversed-phase chromatography of proteins. J. Chromatogr. A 1984, 317:141-155.
106. Kramarczyk J.F., Kelley B.D., Coffman J.L. High-throughput screening of chromatographic separations. II. Hydrophobic interaction. Biotechnol. Bioengin. 2008, 100:707-720.
107. Clore G.M., Martin S.R., Gronenborn A.M. Solution structure of human growth hormone releasing factor: combined use of circular dichroism and nuclear magnetic resonance spectroscopy. J. Mol. Biol. 1986, 191:553-561.
108. Jones C. Applications of nuclear magnetic resonance, circular dichroism and fluorescence spectroscopy to the characterization of biological products. Biologicals 1993, 21:119-124.
109. Böhm G., Muhr R., Jaenicke R. Quantitative analysis of protein far UV circular dichroism spectra by neural networks. Protein Eng. 1992, 5:191-195.
110. Doglia S.M., Ami D., Natalello A., Gatti-Lafranconi P., Lotti M. Fourier transform infrared spectroscopy analysis of the conformational quality of recombinant proteins within inclusion bodies. Biotechnol. J. 2008, 3:193-201.
111. Ladokhin A.S. Fluorescence Spectroscopy in Peptide and Protein Analysis. Encyclopedia of Analytical Chemistry 2006, John Wiley & Sons, Ltd.
112. Schuler B. Single-molecule fluorescence spectroscopy of protein folding. ChemPhysChem 2005, 6:1206-1220.
113. Lakowicz J.R., Masters B.R. Principles of fluorescent spectroscopy, third edition. J. Biomed. Opt. 2008, 13:1-2.
114. Hempe J.M., McGehee A.M., Hsia D., Chalew S.A. Characterization of unstable hemoglobin A1c complexes by dynamic capillary isoelectric focusing. Anal. Biochem. 2012, 424:149-155.
115. Yang C., Zhang W., Zhang J., Duan J., Zhang Y. Protocol of capillary isoelectric focusing to separate extremely acidic and basic proteins. J. Sep. Sci. 2005, 28:78-86.
116. Giddings J. Field-flow fractionation: analysis of macromolecular, colloidal, and particulate materials. Science 1993, 260:1456-1465.
117. Trivedi V.D., Yu C., Veeramuthu B., Francis S., Chang D.K. Fusion induced aggregation of model vesicles studied by dynamic and static light scattering. Chem. Phys. Lipids 2000, 107:99-106.
118. Rathore A.S., Sobacke S.E., Kocot T.J., Morgan D.R., Dufield R.L., Mozier N.M. Analysis for residual host cell proteins and DNA in process streams of a recombinant protein product expressed in Escherichia coli cells. J. Pharm. Biomed. Anal. 2003, 32:1199-1211.
119. Wan M., Wang Y., Rabideau S., Moreadith R., Schrimsher J., Conn G. An enzyme-linked immunosorbent assay for host cell protein contaminants in recombinant PEGylated staphylokinase mutant SY161. J. Pharm. Biomed. Anal. 2002, 28:953-963.
120. 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.
121. O'Keefe D.O., DePhillips P., Will M.L. Identification of an Escherichia coli protein impurity in preparations of a recombinant pharmaceutical. Pharm. Res. 1993, 10:975-979.