Case studies applying biophysical techniques to better characterize protein aggregates and particulates of varying size

Biophysics for Therapeutic Protein Development

Volumn , Issue , 2013, Pages 205-243

  Wang, Tingting ^a   Joshi, Sangeeta B ^a   Kumru, Ozan S ^a   Telikepalli, Srivalli ^a   Russell Middaugh, C ^a   Volkin, David B ^a  

^a UNIVERSITY OF KANSAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84894465635     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4614-4316-2_9     Document Type: Chapter

References (157)

1. Aguzzi A, O'Connor T (2010) Protein aggregation diseases: pathogenicity and therapeutic perspectives. Nat Rev Drug Discov 9(3):237-248.
2. Ahrer K, Buchacher A, Iberer G, Josic D, Jungbauer A (2003) Analysis of aggregates of human immunoglobulin G using size-exclusion chromatography, static and dynamic light scattering. J Chromatogr A 1009(1-2):89-96.
3. Arakawa T, Ejima D, Li T, Philo JS (2010) The critical role of mobile phase composition in size exclusion chromatography of protein pharmaceuticals. J Pharm Sci 99(4):1674-1692.
4. Barnard JG, Singh S, Randolph TW, Carpenter JF (2010) Subvisible particle counting provides a sensitive method of detecting and quantifying aggregation of monoclonal antibody caused by freeze-thawing: insights into the roles of particles in the protein aggregation pathway. J Pharm Sci 100(2):492-503.
5. Barnard JG, Rhyner MN, Carpenter JF (2012) Critical evaluation and guidance for using the coulter method for counting subvisible particles in protein solutions. J Pharm Sci 101(1):140-153.
6. Berkowitz SA (2006) Role of analytical ultracentrifugation in assessing the aggregation of protein biopharmaceuticals. AAPS J 8(3):E590-E605.
7. Bhambhani A, Kissmann JM, Joshi SB, Volkin DB, Kashi RS, Middaugh CR (2012) Formulation design and high-throughput excipient selection based on structural integrity and conformational stability of dilute and highly concentrated IgG1 monoclonal antibody solutions. J Pharm Sci 101(3):1120-1135.
8. Bond MD, Panek ME, Zhang Z et al (2010) Evaluation of a dual-wavelength size exclusion HPLC method with improved sensitivity to detect protein aggregates and its use to better characterize degradation pathways of an IgG1 monoclonal antibody. J Pharm Sci 99(6):2582-2597.
9. Burg TP, Godin M, Knudsen SM et al (2007) Weighing of biomolecules, single cells and single nanoparticles in fluid. Nature 446(7139):1066-1069.
10. Calamai M, Canale C, Relini A, Stefani M, Chiti F, Dobson CM (2005) Reversal of protein aggregation provides evidence for multiple aggregated States. J Mol Biol 346(2):603-616.
11. Cao S, Pollastrini J, Jiang Y (2009) Separation and characterization of protein aggregates and particles by field flow fractionation. Curr Pharm Biotechnol 10(4):382-390.
12. Cao X, Masatani P, Torraca G, Wen ZQ (2010) Identification of a mixed microparticle by combined microspectroscopic techniques: a real forensic case study in the biopharmaceutical industry. Appl Spectrosc 64(8):895-900.
13. Carpenter JF, Randolph TW, Jiskoot W et al (2009) Overlooking subvisible particles in therapeutic protein products: gaps that may compromise product quality. J Pharm Sci 98(4):1201-1205.
14. Carpenter JF, Randolph TW, Jiskoot W, Crommelin DJ, Middaugh CR, Winter G (2010a) Potential inaccurate quantitation and sizing of protein aggregates by size exclusion chromatography:essential need to use orthogonal methods to assure the quality of therapeutic protein products. J Pharm Sci 99(5):2200-2208.
15. Carpenter J, Cherney B, Lubinecki A et al (2010b) Meeting report on protein particles and immunogenicity of therapeutic proteins: filling in the gaps in risk evaluation and mitigation. Biologicals 38(5):602-611.
16. Chait BT (2011) Mass spectrometry in the postgenomic era. Annu Rev Biochem 80:239-246.
17. Cheng X, van Breemen RB (2005) Mass spectrometry-based screening for inhibitors of betaamyloid protein aggregation. Anal Chem 77(21):7012-7015.
18. Chrai S, Clayton R, Mestrandrea L et al (1987) Limitations in the use of HIAC for product particle counting. J Parenter Sci Technol 41(6):209-214.
19. Colton RJ, Baselt DR, Dufrene YF, Green JB, Lee GU (1997) Scanning probe microscopy. Curr Opin Chem Biol 1(3):370-377.
20. Costello MA, Woititz C, Defeo J et al (1992) Characterization of humanized anti-tac monoclonalantibody by traditional separation techniques and capillary electrophoresis. J Liq Chromatogr 15(6-7):1081-1097.
21. Cram LS (2002) Flow cytometry, an overview. Methods Cell Sci 24(1-3):1-9.
22. Dam J, Schuck P (2004) Calculating sedimentation coefficient distributions by direct modeling of sedimentation velocity concentration profiles. Meth Enzymol 384:185-212.
23. David Bernard Williams CBC (2009) The transmission electron microscope. Springer, New York.
24. Demeule B, Gurny R, Arvinte T (2007a) Detection and characterization of protein aggregates by fluorescence microscopy. Int J Pharm 329(1-2):37-45.
25. Demeule B, Lawrence MJ, Drake AF, Gurny R, Arvinte T (2007b) Characterization of protein aggregation: the case of a therapeutic immunoglobulin. Biochim Biophys Acta 1774(1):146-153.
26. Demeule B, Palais C, Machaidze G, Gurny R, Arvinte T (2009) New methods allowing the detection of protein aggregates: a case study on trastuzumab. MAbs 1(2):142-150.
27. Demeule B, Messick S, Shire SJ, Liu J (2010) Characterization of particles in protein solutions:reaching the limits of current technologies. AAPS J 12(4):708-715.
28. Engelhard M, Evans PA (1995) Kinetics of interaction of partially folded proteins with a hydrophobic dye: evidence that molten globule character is maximal in early folding intermediates. Protein sci 4(8):1553-1562.
29. Engelsman J, Garidel P, Smulders R et al (2011) Strategies for the assessment of protein aggregates in pharmaceutical biotech product development. Pharm Res 28(4):920-933.
30. Erukhimovitch V, Talyshinsky M, Souprun Y, Huleihel M (2002) Spectroscopic characterization of human and mouse primary cells, cell lines and malignant cells. Photochem Photobiol 76(4):446-451.
31. Esue O, Kanai S, Liu J, Patapoff TW, Shire SJ (2009) Carboxylate-dependent gelation of a monoclonal antibody. Pharm Res 26(11):2478-2485.
32. Ferreira GN, da-Silva AC, Tome B (2009) Acoustic wave biosensors: physical models and biological applications of quartz crystal microbalance. Trends Biotechnol 27(12):689-697.
33. Filipe V, Hawe A, Jiskoot W (2010) Critical evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res 27(5):796-810.
34. Filipe V, Poole R, Kutscher M, Forier K, Braeckmans K, Jiskoot W (2011) Fluorescence single particle tracking for the characterization of submicron protein aggregates in biological fluids and complex formulations. Pharm Res 28(5):1112-1120.
35. Flores-Fernandez GM, Sola RJ, Griebenow K (2009) The relation between moisture-induced aggregation and structural changes in lyophilized insulin. J Pharm Pharmacol 61(11):1555-1561.
36. Fradkin AH, Carpenter JF, Randolph TW (2011) Glass particles as an adjuvant: a model for adverse immunogenicity of therapeutic proteins. J Pharm Sci 100(11):4953-4964.
37. Fraunhofer W, Winter G (2004) The use of asymmetrical flow field-flow fractionation in pharmaceutics and biopharmaceutics. Eur J Pharm Biopharm 58(2):369-383.
38. Gabrielson JP, Arthur KK (2011) Measuring low levels of protein aggregation by sedimentation velocity. Methods 54(1):83-91.
39. Gabrielson JP, Brader ML, Pekar AH et al (2007) Quantitation of aggregate levels in a recombinant humanized monoclonal antibody formulation by size-exclusion chromatography, asymmetrical flow field flow fractionation, and sedimentation velocity. J Pharm Sci 96(2):268-279.
40. Ginsberg MH, Frelinger AL, Lam SC et al (1990) Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein IIb-IIIa with conformation-specific monoclonal antibodies. Blood 76(10):2017-2023.
41. Giselle M, Flores-Fernandez G, Solá R, Griebenow K (2009) The relation between moistureinduced aggregation and structural changes in lyophilized insulin. J Pharm Pharmacol 61(11):1555-1561.
42. Greenwood R (2003) Review of the measurement of zeta potentials in concentrated aqueous suspensions using electroacoustics. Adv Colloid Interface Sci 106:55-81.
43. Grillberger L, Kreil TR, Nasr S, Reiter M (2009) Emerging trends in plasma-free manufacturing of recombinant protein therapeutics expressed in mammalian cells. Biotechnol J 4(2):186-201.
44. Han M, Phan D, Nightlinger N et al (2006) Optimization of CE-SDS method for antibody separation based on multi-users experimental practices. Chromatographia 64:334-342.
45. Harding SA, Din JN, Sarma J et al (2007) Flow cytometric analysis of circulating plateletmonocyte aggregates in whole blood: methodological considerations. Thromb Haemost 98(2):451-456.
46. Harper JD, Lieber CM, Lansbury PT Jr (1997) Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer's disease amyloid-beta protein. Chem Biol 4(12):951-959.
47. Hawe A, Friess W, Sutter M, Jiskoot W (2008a) Online fluorescent dye detection method for the characterization of immunoglobulin G aggregation by size exclusion chromatography and asymmetrical flow field flow fractionation. Anal Biochem 378(2):115-122.
48. Hawe A, Sutter M, Jiskoot W (2008b) Extrinsic fluorescent dyes as tools for protein characterization. Pharm Res 25(7):1487-1499.
49. Hawe A, Hulse WL, Jiskoot W, Forbes RT (2011) Taylor dispersion analysis compared to dynamic light scattering for the size analysis of therapeutic peptides and proteins and their aggregates. Pharm Res 28(9):2302-2310.
50. He F, Phan DH, Hogan S et al (2010) Detection of IgG aggregation by a high throughput method based on extrinsic fluorescence. J Pharm Sci 99(6):2598-2608.
51. Heldt CL, Sorci M, Posada D, Hirsa A, Belfort G (2011) Detection and reduction of microaggregates in insulin preparations. Biotechnol Bioeng 108(1):237-241.
52. Hillger F, Nettels D, Dorsch S, Schuler B (2007) Detection and analysis of protein aggregation with confocal single molecule fluorescence spectroscopy. J Fluoresc 17(6):759-765.
53. Houde D, Arndt J, Domeier W, Berkowitz S, Engen JR (2009) Characterization of IgG1 conformation and conformational dynamics by hydrogen/deuterium exchange mass spectrometry. Anal Chem 81(14):5966.
54. Huang C-T, Sharma D, Oma P, Krishnamurthy R (2009) Quantitation of protein particles in parenteral solutions using micro-flow imaging. J Pharm Sci 98(9):3058-3071.
55. Hughes H, Morgan C, Brunyak E et al (2009) A multi-tiered analytical approach for the analysis and quantitation of high-molecular-weight aggregates in a recombinant therapeutic glycoprotein. AAPS J 11(2):335-341.
56. Hunt G, Moorhouse KG, Chen AB (1996) Capillary isoelectric focusing and sodium dodecyl sulfate- capillary gel electrophoresis of recombinant humanized monoclonal antibody HER2. J Chromatogr A 744(1-2):295-301.
57. Jorio H, Tran R, Meghrous J, Bourget L, Kamen A (2006) Analysis of baculovirus aggregates using flow cytometry. J Virol Methods 134(1-2):8-14.
58. Joseph Goldstein DN, Joy D, Lyman C, Echlin P, Lifshin E, Sawyer L, Michael J (2003) Scanning electron microscopy and X-ray microanalysis, 3rd edn. Plenum, New York.
59. Joubert MK, Luo Q, Nashed-Samuel Y, Wypych J, Narhi LO (2011) Classification and characterization of therapeutic antibody aggregates. J Biol Chem 286(28):25118-25133.
60. Kaddis CS, Lomeli SH, Yin S et al (2007) Sizing large proteins and protein complexes by electrospray ionization mass spectrometry and ion mobility. J Am Soc Mass Spectrom 18(7):1206-1216.
61. Kaltashov IA, Bobst CE, Abzalimov RR, Wang G, Baykal B, Wang S (2012) Advances and challenges in analytical characterization of biotechnology products: mass spectrometry-based approaches to study properties and behavior of protein therapeutics. Biotechnol Adv 30(1):210-222.
62. Kamerzell TJ, Esfandiary R, Joshi SB, Middaugh CR, Volkin DB (2011) Protein-excipient interactions:mechanisms and biophysical characterization applied to protein formulation development. Adv Drug Deliv Rev 63(13):1118-1159.
63. Kheterpal I, Wetzel R (2006) Hydrogen/deuterium exchange mass spectrometry-a window into amyloid structure. Acc Chem Res 39(9):584-593.
64. Khurana R, Uversky VN, Nielsen L, Fink AL (2001) Is Congo red an amyloid-specific dye? J Biol Chem 276(25):22715-22721.
65. Kiese S, Papppenberger A, Friess W, Mahler HC (2008) Shaken, not stirred: mechanical stress testing of an IgG1 antibody. J Pharm Sci 97(10):4347-4366.
66. Kiese S, Pappenberger A, Friess W, Mahler H-C (2010) Equilibrium studies of protein aggregates and homogeneous nucleation in protein formulation. J Pharm Sci 99(2):632-644.
67. Kilar F (2003) Recent applications of capillary isoelectric focusing. Electrophoresis 24(22-23):3908-3916.
68. Kim YS, Randolph TW, Manning MC, Stevens FJ, Carpenter JF (2003) Congo red populates partially unfolded states of an amyloidogenic protein to enhance aggregation and amyloid fibril formation. J Biol Chem 278(12):10842-10850.
69. Knowles TPJ, Devlin GL, Dobson CM, Welland ME (2011) Probing protein aggregation with quartz crystal microbalances. In: Hill AF, Barnham KJ, Bottomley SP, Cappai R (eds) Protein folding, misfolding, and disease, vol 752, 1st edn. Humana Press, New York.
70. Konermann L, Pan J, Liu YH (2011) Hydrogen exchange mass spectrometry for studying protein structure and dynamics. Chem Soc Rev 40(3):1224-1234.
71. Kraly J, Fazal MA, Schoenherr RM et al (2006) Bioanalytical applications of capillary electrophoresis. Anal Chem 78(12):4097-4110.
72. Kukrer B, Filipe V, van Duijn E et al (2010) Mass spectrometric analysis of intact human monoclonal antibody aggregates fractionated by size-exclusion chromatography. Pharm Res 27(10):2197-2204.
73. Lee H, Kirchmeier M, Mach H (2011) Monoclonal antibody aggregation intermediates visualized by atomic force microscopy. J Pharm Sci 100(2):416-423.
74. Li B, Flores J, Corvari V (2007) A simple method for the detection of insoluble aggregates in protein formulations. J Pharm Sci 96(7):1840-1843.
75. Li Y, Mach H, Blue JT (2011) High throughput formulation screening for global aggregation behaviors of three monoclonal antibodies. J Pharm Sci 100(6):2120-2135.
76. Lichtman JW, Conchello JA (2005) Fluorescence microscopy. Nat Methods 2(12):910-919.
77. Liu J, Shire SJ (1999) Analytical ultracentrifugation in the pharmaceutical industry. J Pharm Sci 88(12):1237-1241.
78. Liu J, Andya JD, Shire SJ (2006) A critical review of analytical ultracentrifugation and field flow fractionation methods for measuring protein aggregation. AAPS J 8(3):E580-E589.
79. Liu W, Swift R, Torraca G et al (2010) Root cause analysis of tungsten-induced protein aggregation in pre-filled syringes. PDA J Pharm Sci Technol 64(1):11-19.
80. Liu L, Ammar DA, Ross LA, Mandava N, Kahook MY, Carpenter JF (2011) Silicone oil microdroplets and protein aggregates in repackaged bevacizumab and ranibizumab: effects of long-term storage and product mishandling. Invest Ophthalmol Vis Sci 52(2):1023-1034.
81. Lomakin A, Benedek GB, Teplow DB (1999) Monitoring protein assembly using quasielastic light scattering spectroscopy. Methods Enzymol 309:429-459.
82. Lubiniecki A, Volkin DB, Federici M et al (2010) Comparability assessments of process and product changes made during development of two different monoclonal antibodies. Biologicals 39(1):9-22.
83. Ludwig DB, Trotter JT, Gabrielson JP, Carpenter JF, Randolph TW (2011) Flow cytometry:a promising technique for the study of silicone oil-induced particulate formation in protein formulations. Anal Biochem 410(2):191-199.
84. Luo Y, Lu Z, Raso SW, Entrican C, Tangarone B (2009) Dimers and multimers of monoclonal IgG1 exhibit higher in vitro binding affinities to Fcgamma receptors. MAbs 1(5):491-504.
85. Luo Q, Joubert MK, Stevenson R, Ketchem RR, Narhi LO, Wypych J (2011) Chemical modifications in therapeutic protein aggregates generated under different stress conditions. J Biol Chem 286(28):25134-25144.
86. Maas C, Hermeling S, Bouma B, Jiskoot W, Gebbink MF (2007) A role for protein misfolding in immunogenicity of biopharmaceuticals. J Biol Chem 282(4):2229-2236.
87. Mach H, Arvinte T (2011) Addressing new analytical challenges in protein formulation development. Eur J Pharm Biopharm 78(2):196-207.
88. Mach H, Middaugh CR (2011) Ultraviolet spectroscopy as a tool in therapeutic protein development. J Pharm Sci 100(4):1214-1227.
89. Mach H, Bhambhani A, Meyer BK et al (2011) The use of flow cytometry for the detection of subvisible particles in therapeutic protein formulations. J Pharm Sci 100(5):1671-1678.
90. Maddux NR, Joshi SB, Volkin DB, Ralston JP, Middaugh CR (2011) Multidimensional methods for the formulation of biopharmaceuticals and vaccines. J Pharm Sci 100(10):4171-4197.
91. Madsen R, Cherris R, Shabushnig JG, Hunt DG (2009) Visible particulates in injections-a history and a proposal to revise USP general chapter injections (1). Pharmacop Forum 35:1383-1387.
92. Mahler HC, Muller R, Friess W, Delille A, Matheus S (2005) Induction and analysis of aggregates in a liquid IgG1-antibody formulation. Eur J Pharm Biopharm 59(3):407-417.
93. Mahler H-C, Friess W, Grauschopf U, Kiese S (2009) Protein aggregation: pathways, induction factors and analysis. J Pharm Sci 98(9):2909-2934.
94. Majumdar S, Ford BM, Mar KD, Sullivan VJ, Ulrich RG, D'souza AJM (2011) Evaluation of the effect of syringe surfaces on protein formulations. J Pharm Sci 100(7):2563-2573.
95. Marcsisin SR, Engen JR (2010) Hydrogen exchange mass spectrometry: what is it and what can it tell us? Anal Bioanal Chem 397(3):967-972.
96. Markovich RJ, Taylor AK, Rosen J (1997) Drug migration from the adhesive matrix to the polymer film laminate facestock in a transdermal nitroglycerin system. J Pharm Biomed Anal 16(4):651-660.
97. Michel Godin AKB, Burg TP, Babcock K, Manalis SR (2007) Measuring the mass, density, and size of particles and cells using a suspended microchannel resonator. Appl Phys Lett 91:3.
98. Michels DA, Brady LJ, Guo A, Balland A (2007) Fluorescent derivatization method of proteins for characterization by capillary electrophoresis-sodium dodecyl sulfate with laser-induced fluorescence detection. Anal Chem 79(15):5963-5971.
99. Middaugh CR, Joshi SB (2011) Spectroscopy of vaccines. In: Singh M, Srivastava IK (eds) Development of vaccines, from discovery to clinical testing. Wiley, Hoboken, pp 263-292.
100. Mire-Sluis A, Cherney B, Madsen R, Polozova A, Rosenberg A, Smith H, Arora T, Narhi L (2011) Analysis and immunogenic potential of aggregates and particles. BioProcess Int 9(10):38-43.
101. Murphy RM (1997) Static and dynamic light scattering of biological macromolecules: what can we learn? Curr Opin Biotechnol 8(1):25-30.
102. Naiki H, Higuchi K, Hosokawa M, Takeda T (1989) Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, thioflavin T1. Anal Biochem 177(2):244-249.
103. Narhi LO, Schmit J, Bechtold-Peters K, Sharma D (2011) Classification of protein aggregates. J Pharm Sci 101(2):493-498.
104. Nayak A, Colandene J, Bradford V, Perkins M (2011) Characterization of subvisible particle formation during the filling pump operation of a monoclonal antibody solution. J Pharm Sci 100(10):4198-4204.
105. Nettleton EJ, Tito P, Sunde M, Bouchard M, Dobson CM, Robinson CV (2000) Characterization of the oligomeric states of insulin in self-assembly and amyloid fibril formation by mass spectrometry. Biophys J 79(2):1053-1065.
106. O'Sullivan CK, Guilbault GG (1999) Commercial quartz crystal microbalances - theory and applications. Biosens Bioelectron 14(8-9):663-670.
107. Oliva A, Llabres M, Farina JB (2001) Comparative study of protein molecular weights by sizeexclusion chromatography and laser-light scattering. J Pharm Biomed Anal 25:833-841.
108. Pease LF 3rd, Elliott JT, Tsai DH, Zachariah MR, Tarlov MJ (2008) Determination of protein aggregation with differential mobility analysis: application to IgG antibody. Biotechnol Bioeng 101(6):1214-1222.
109. Philo JS (2006) Is any measurement method optimal for all aggregate sizes and types? AAPS J 8(3):E564-E571.
110. Philo JS (2009) A critical review of methods for size characterization of non-particulate protein aggregates. Curr Pharm Biotechnol 10(4):359-372.
111. Philo JS, Arakawa T (2009) Mechanisms of protein aggregation. Curr Pharm Biotechnol 10(4):348-351.
112. Prati S, Joseph E, Sciutto G, Mazzeo R (2010) New advances in the application of FTIR microscopy and spectroscopy for the characterization of artistic materials. Acc Chem Res 43(6):792-801.
113. Qi P, Volkin DB, Zhao H et al (2009) Characterization of the photodegradation of a human IgG1 monoclonal antibody formulated as a high-concentration liquid dosage form. J Pharm Sci 98(9):3117-3130.
114. Remmele RL Jr, Callahan WJ, Krishnan S et al (2006) Active dimer of Epratuzumab provides insight into the complex nature of an antibody aggregate. J Pharm Sci 95(1):126-145.
115. Reschiglian P, Zattoni A, Roda B, Michelini E, Roda A (2005) Field-flow fractionation and biotechnology. Trends Biotechnol 23(9):475-483.
116. Rhyner MN (2011) The Coulter principle for analysis of subvisible particles in protein formulations. AAPS J 13(1):54-58.
117. Roberts GS, Yu S, Zeng Q et al (2012) Tunable pores for measuring concentrations of synthetic and biological nanoparticle dispersions. Biosens Bioelectron 31(1):17-25.
118. Roda B, Zattoni A, Reschiglian P et al (2009) Field-flow fractionation in bioanalysis: a review of recent trends. Anal Chim Acta 635(2):132-143.
119. Rosenberg AS (2006) Effects of protein aggregates: an immunologic perspective. AAPS J 8(3):E501-E507.
120. Rosenberg E, Hepbildikler S, Kuhne W, Winter G (2009) Ultrafiltration concentration of monoclonal antibody solutions: development of an optimized method minimizing aggregation. J Membr Sci 342(1-2):50-59.
121. Ross S, Morrison ID (2002) Colloidal dispersions. Wiley Interscience, New York.
122. Rumi Chunara MG, Knudsen SM, Manalis SR (2007) Mass-based readout for agglutination assays. Appl Phys Lett 91:3.
123. Rustandi RR, Washabaugh MW, Wang Y (2008) Applications of CE SDS gel in development of biopharmaceutical antibody-based products. Electrophoresis 29(17):3612-3620.
124. Salas-Solano O, Tomlinson B, Du S, Parker M, Strahan A, Ma S (2006) Optimization and validation of a quantitative capillary electrophoresis sodium dodecyl sulfate method for quality control and stability monitoring of monoclonal antibodies. Anal Chem 78(18):6583-6594.
125. Salman A, Erukhimovitch V, Talyshinsky M, Huleihil M, Huleihel M (2002) FTIR spectroscopic method for detection of cells infected with herpes viruses. Biopolymers 67(6):406-412.
126. Saluja A, Kalonia DS (2008) Nature and consequences of protein-protein interactions in high protein concentration solutions. Int J Pharm 358(1-2):1-15.
127. Sauerbrey G (1959) Use of quartz vibration for weighing thin films on a microbalance. J Phys 155:206-212.
128. Schmitt C, Bovay C, Rouvet M, Shojaei-Rami S, Kolodziejczyk E (2007) Whey protein soluble aggregates from heating with NaCl: physicochemical, interfacial, and foaming properties. Langmuir 23(8):4155-4166.
129. Schuck P (2000) Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and Lamm equation modeling. Biophys J 78(3):1606-1619.
130. Schuck P (2004) A model for sedimentation in inhomogeneous media. II. Compressibility of aqueous and organic solvents. Biophys Chem 108(1-3):201-214.
131. Sejersen M, Salomonsena T, Ipsen R, Clark R, Rolin C, Engelsen S (2007) Zeta potential of pectinstabilised casein aggregates in acidified milk drinks. Int Dairy J 17:302-307.
132. Shapiro HM (1995) Practical flow cytometry. Wiley-Liss, New york.
133. Sharma DK, Oma P, Pollo MJ, Sukumar M (2010a) Quantification and characterization of subvisible proteinaceous particles in opalescent mAb formulations using micro-flow imaging. J Pharm Sci 99(6):2628-2642.
134. Sharma DK, King D, Oma P, Merchant C (2010b) Micro-flow imaging: flow microscopy applied to sub-visible particulate analysis in protein formulations. AAPS J 12(3):455-464.
135. Singh SK, Afonina N, Awwad M et al (2010) An industry perspective on the monitoring of subvisible particles as a quality attribute for protein therapeutics. J Pharm Sci 99(8):3302-3321.
136. Strehl R, Rombach-Riegraf V, Diez M et al (2011) Discrimination between silicone oil droplets and protein aggregates in biopharmaceuticals: a novel multiparametric image filter for subvisible particles in microflow imaging analysis. Pharm Res 27:1-9.
137. Sutter M, Oliveira S, Sanders NN et al (2007) Sensitive spectroscopic detection of large and denatured protein aggregates in solution by use of the fluorescent dye Nile red. J Fluoresc 17(2):181-192.
138. Thillaivinayagalingam P, Gommeaux J, McLoughlin M, Collins D, Newcombe AR (2010) Biopharmaceutical production: Applications of surface plasmon resonance biosensors. J Chromatogr B Analyt Technol Biomed Life Sci 878(2):149-153.
139. Tobler SA, Fernandez EJ (2002) Structural features of interferon-gamma aggregation revealed by hydrogen exchange. Protein sci 11(6):1340-1352.
140. Torraca G, Wen Z (2005) Forensic investigation of biopharmaceutical manufacturing incidents by light microscopy, ftir microscopy, scanning electron microscopy and energy dispersive X-ray spectrometry. Microsc Microanal 11:1224-1225.
141. Tyagi AK, Randolph TW, Dong A, Maloney KM, Hitscherich C Jr, Carpenter JF (2009) IgG particle formation during filling pump operation: a case study of heterogeneous nucleation on stainless steel nanoparticles. J Pharm Sci 98(1):94-104.
142. Uetrecht C, Rose RJ, van Duijn E, Lorenzen K, Heck AJ (2010) Ion mobility mass spectrometry of proteins and protein assemblies. Chem Soc Rev 39(5):1633-1655.
143. Uskokovic V, Castiglione Z, Cubas P, Zhu L, Li W, Habelitz S (2010) Zeta-potential and particle size analysis of human amelogenins. J Dent Res 89(2):149-153.
144. Van Buren N, Rehder D, Gadgil H, Matsumura M, Jacob J (2009) Elucidation of two major aggregation pathways in an IgG2 antibody. J Pharm Sci 98(9):3013-3030.
145. van Duijn E (2010) Current limitations in native mass spectrometry based structural biology. J Am Soc Mass Spectrom 21(6):971-978.
146. Wall J, Solomon A (1999) Flow cytometric characterization of amyloid fibrils. Methods Enzymol 309:460-466.
147. Wang W, Nema S, Teagarden D (2010) Protein aggregation-pathways and influencing factors. Int J Pharm 390(2):89-99.
148. Wang G, Abzalimov RR, Kaltashov IA (2011) Direct monitoring of heat-stressed biopolymers with temperature-controlled electrospray ionization mass spectrometry. Anal Chem 83(8):2870-2876.
149. Wang G, Johnson AJ, Kaltashov IA (2012) Evaluation of electrospray ionization mass spectrometry as a tool for characterization of small soluble protein aggregates. Anal Chem 84(3):1718-1724.
150. Watson JT, Sparkman OD (2008) Introduction to mass spectrometry: instrumentation, applications, and strategies for data interpretation. Wiley, Chichester.
151. Wear MA, Patterson A, Malone K, Dunsmore C, Turner NJ, Walkinshaw MD (2005) A surface plasmon resonance-based assay for small molecule inhibitors of human cyclophilin A. Anal Biochem 345(2):214-226.
152. Wen J, Arakawa T, Philo JS (1996) Size-exclusion chromatography with on-line light-scattering, absorbance and refractive index detectors for studying proteins and their interactions. Anal Biochem 240:155-166.
153. Wuchner K, Büchler J, Spycher R, Dalmonte P, Volkin DB (2010) Development of a microflow digital imaging assay to characterize protein particulates during storage of a high concentration IgG1 monoclonal antibody formulation. J Pharm Sci 99(8):3343-3361.
154. Ye H (2006) Simultaneous determination of protein aggregation, degradation, and absolute molecular weight by size exclusion chromatography-multiangle laser light scattering. Anal Biochem 356(1):76-85.
155. Yohannes G, Jussila M, Hartonen K, Riekkola ML (2011) Asymmetrical flow field-flow fractionation technique for separation and characterization of biopolymers and bioparticles. J Chromatogr A 1218:4104-4116.
156. Zhang A, Qi W, Singh SK, Fernandez EJ (2011) A new approach to explore the impact of freezethaw cycling on protein structure: hydrogen/deuterium exchange mass spectrometry (HX-MS). Pharm Res 28(5):1179-1193.
157. Zhang A, Singh SK, Shirts MR, Kumar S, Fernandez EJ (2012) Distinct aggregation mechanisms of monoclonal antibody under thermal and freeze-thaw stresses revealed by hydrogen exchange. Pharm Res 29(1):236-250.