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Review

Forced degradation of recombinant monoclonal antibodies: A practical guide

, , , , , , , , , & show all
Pages 1217-1230 | Received 22 Jun 2017, Accepted 11 Aug 2017, Published online: 21 Sep 2017

References

  • Blessy M, Patel R, Prajapati P, Agrawal Y. Develpment of forced degradation and stability indicating studies of drugs- a review. J Pharm Anal. 2014;4(3):159-65. doi:10.1016/j.jpha.2013.09.003
  • Hawe A, Wiggenhorn M, van de Weert M, Garbe JH, Mahler HC, Jiskoot W. Forced degradation of therapeutic proteins. J Pharm Sci. 2012;101(3):895-913. doi:10.1002/jps.22812. PMID:22083792
  • Kilck S, Muijselaar P, Waterval J, Eichinger T, Korn C, Gerding T, Debets A, Sanger-van de Griend C, Van den Beld C, Somsen G., et al. Toward a generic approach for stress testing of drug substances and drug products. Pharm Technol. 2005, February, 48-66
  • Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res. 2010;27(4):544-75. doi:10.1007/s11095-009-0045-6. PMID:20143256
  • Tamizi E, Jouyban A. Forced degradation studies of biopharmaceuticals: Selection of stress conditions. Eur J Pharm Biopharm. 2016;98:26-46. doi:10.1016/j.ejpb.2015.10.016. PMID:26542454
  • Alexander AJ, Hughes DE Monitoring of IgG antibody thermal stability by micellar electrokinetic capillary chromatography and matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem. 1995;67(20):3626-32. doi:10.1021/ac00116a002. PMID:8644915
  • Andya JD, Maa YF, Costantino HR, Nguyen PA, Dasovich N, Sweeney TD, Hsu CC, Shire SJ. The effect of formulation excipients on protein stability and aerosol performance of spray-dried powders of a recombinant humanized anti-IgE monoclonal antibody. Pharm Res. 1999;16(3):350-58. doi:10.1023/A:1018805232453. PMID:10213364
  • Banks DD, Hambly DM, Scavezze JL, Siska CC, Stackhouse NL, Gadgil HS. The effect of sucrose hydrolysis on the stability of protein therapeutics during accelerated formulation studies. J Pharm Sci. 2009;98(12):4501-10. doi:10.1002/jps.21749. PMID:19388069
  • Fesinmeyer RM, Hogan S, Saluja A, Brych SR, Kras E, Narhi LO, Brems DN, Gokarn YR. Effect of ions on agitation- and temperature-induced aggregation reactions of antibodies. Pharm Res. 2009;26(4):903-13. doi:10.1007/s11095-008-9792-z. PMID:19104916
  • Franey H, Brych SR, Kolvenbach CG, Rajan RS. Increased aggregation propensity of IgG2 subclass over IgG1: Role of conformational changes and covalent character in isolated aggregates. Protein Sci. 2010;19(9):1601-15. doi:10.1002/pro.434. PMID:20556807
  • Hawe A, Kasper JC, Friess W, Jiskoot W. Structural properties of monoclonal antibody aggregates induced by freeze-thawing and thermal stress. Eur J Pharm Sci. 2009;38(2):79-87. doi:10.1016/j.ejps.2009.06.001. PMID:19540340
  • Jiskoot W, Beuvery EC, De Koning AA, Herron JN, Crommelin DJ. Analytical approaches to the study of monoclonal antibody stability. Pharm Res. 1990;7(12):1234-41.doi:10.1023/A:1015925519154. PMID:2095560
  • Joubert MK, Luo Q, Nashed-Samuel Y, Wypych J, Narhi LO. Classification and characterization of therapeutic antibody aggregates. J Biol Chem. 2011;286(28):25118-33. doi:10.1074/jbc.M110.160457. PMID:21454532
  • Liu H, Gaza-Bulseco G, Sun J. Characterization of the stability of a fully human monoclonal IgG after prolonged incubation at elevated temperature. J Chromatogr B Analyt Technol Biomed Life Sci. 2006;837(1–2):35-43. doi:10.1016/j.jchromb.2006.03.053. PMID:16644295
  • Luo Q, Joubert MK, Stevenson R, Ketchem RR, Narhi LO, Wypych J Chemical modifications in therapeutic protein aggregates generated under different stress conditions. J Biol Chem. 2011;286(28):25134-44. doi:10.1074/jbc.M110.160440. PMID:21518762
  • Telikepalli SN, Kumru OS, Kalonia C, Esfandiary R, Joshi SB, Middaugh CR, Volkin D B. Structural characterization of IgG1 mAb aggregates and particles generated under various stress conditions. J Pharm Sci. 2014;103(3):796-809. doi:10.1002/jps.23839. PMID:24452866
  • Van BN, Rehder D, Gadgil H, Matsumura M, Jacob J. Elucidation of two major aggregation pathways in an IgG2 antibody. J Pharm Sci. 2009;98(9):3013-30. doi:10.1002/jps.21514. PMID:18680168
  • Zhang A, Singh SK, Shirts MR, Kumar S, Fernandez EJ. Distinct aggregation mechanisms of monoclonal antibody under thermal and freeze-thaw stresses revealed by hydrogen exchange. Pharm Res. 2012;29(1):236-50. doi:10.1007/s11095-011-0538-y. PMID:21805212
  • Paborji M, Pochopin NL, Coppola WP, Bogardus JB Chemical and physical stability of chimeric L6, a mouse-human monoclonal antibody. Pharm Res. 1994;11(5):764-71. doi:10.1023/A:1018948901599. PMID:8058650
  • Cordoba AJ, Shyong BJ, Breen D, Harris RJ. Non-enzymatic hinge region fragmentation of antibodies in solution. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;818(2):115-21. doi:10.1016/j.jchromb.2004.12.033. PMID:15734150
  • Dillon TM, Bondarenko PV, Speed RM Development of an analytical reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry method for characterization of recombinant antibodies. J Chromatogr A 2004;1053(1–2):299-305. doi:10.1016/S0021-9673(04)01410-4. PMID:15543996
  • Dillon TM, Bondarenko PV, Rehder DS, Pipes GD, Kleemann GR, Ricci MS. Optimization of a reversed-phase high-performance liquid chromatography/mass spectrometry method for characterizing recombinant antibody heterogeneity and stability. J Chromatogr A. 2006;1120(1–2):112-20. doi:10.1016/j.chroma.2006.01.016. PMID:16448656
  • Gaza-Bulseco G., Liu H. Fragmentation of a recombinant monoclonal antibody at various pH. Pharm Res. 2008;25(8):1881-90. doi:10.1007/s11095-008-9606-3. PMID:18473123
  • Liu H, Gaza-Bulseco G, Lundell E Assessment of antibody fragmentation by reversed-phase liquid chromatography and mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;876(1):13-23. doi:10.1016/j.jchromb.2008.10.015. PMID:18993120
  • Xiang T, Lundell E, Sun Z, Liu H Structural effect of a recombinant monoclonal antibody on hinge region peptide bond hydrolysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;858(1–2):254-62. doi:10.1016/j.jchromb.2007.08.043. PMID:17901002
  • Smith MA, Easton M, Everett P, Lewis G, Payne M, Riveros-Moreno V, Allen G. Specific cleavage of immunoglobulin G by copper ions. Int J Pept Protein Res. 1996;48(1):48-55. doi:10.1111/j.1399-3011.1996.tb01105.x. PMID:8844262
  • Ouellette D, Alessandri L, Piparia R, Aikhoje A, Chin A, Radziejewski C, Correia I. Elevated cleavage of human immunoglobulin gamma molecules containing a lambda light chain mediated by iron and histidine. Anal Biochem. 2009;389(2):107-17. doi:10.1016/j.ab.2009.03.027. PMID:19318085
  • Xiao G, Bondarenko PV. Identification and quantification of degradations in the Asp-Asp motifs of a recombinant monoclonal antibody. J. Pharm Biomed Anal. 2008;47(1):23-30. doi:10.1016/j.jpba.2007.11.050. PMID:18201853
  • Li W, Yang B, Zhou D, Xu J, Li W, Suen WC. Identification and characterization of monoclonal antibody fragments cleaved at the complementarity determining region using orthogonal analytical methods. J Chromatogr B Analyt Technol Biomed Life Sci. 2017;1048:121-29. doi:10.1016/j.jchromb.2017.02.019. PMID:28242491
  • Kroon DJ, Baldwin-Ferro A, Lalan P. Identification of sites of degradation in a therapeutic monoclonal antibody by peptide mapping. Pharm. Res. 1992;9(11):1386-93. doi:10.1023/A:1015894409623. PMID:1475223
  • Yan B, Steen S, Hambly D, Valliere-Douglass J, Vanden Bos T, Smallwood S, Yates Z, Arroll T, Han Y, Gadgil H., et al. Succinimide formation at Asn 55 in the complementarity determining region of a recombinant monoclonal antibody IgG1 heavy chain. J Pharm Sci. 2009;98(10):3509-21. doi:10.1002/jps.21655. PMID:19475547
  • Zhang YT, Hu J, Pace AL, Wong R, Wang YJ, Kao YH. Characterization of asparagine 330 deamidation in an Fc-fragment of IgG1 using cation exchange chromatography and peptide mapping. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;965:65-71. doi:10.1016/j.jchromb.2014.06.018. PMID:24999246
  • Lam XM, Yang JY, Cleland JL. Antioxidants for prevention of methionine oxidation in recombinant monoclonal antibody HER2. J Pharm Sci. 1997;86(11):1250-55. doi:10.1021/js970143s. PMID:9383735
  • Chu GC, Chelius D, Xiao G, Khor HK, Coulibaly S, Bondarenko PV. Accumulation of succinimide in a recombinant monoclonal antibody in mildly acidic buffers under elevated temperatures. Pharm Res. 2007;24(6):1145-56. doi:10.1007/s11095-007-9241-4. PMID:17385019
  • Huang HZ, Nichols A, Liu D Direct identification and quantification of aspartyl succinimide in an IgG2 mAb by RapiGest assisted digestion. Anal Chem. 2009;81(4):1686-92. doi:10.1021/ac802708s. PMID:19146457
  • Yu XC, Joe K, Zhang Y, Adriano A, Wang Y, Gazzano-Santoro H, Keck RG, Deperalta G, Ling V. Accurate determination of succinimide degradation products using high fidelity trypsin digestion peptide map analysis. Anal Chem. 2011;83(15):5912-19. doi:10.1021/ac200750u. PMID:21692515
  • Valliere-Douglass J, Jones L, Shpektor D, Kodama P, Wallace A, Balland A, Bailey R, Zhang Y. Separation and characterization of an IgG2 antibody containing a cyclic imide in CDR1 of light chain by hydrophobic interaction chromatography and mass spectrometry. Anal Chem. 2008;80(9):3168-74. doi:10.1021/ac702245c. PMID:18355059
  • Cacia J, Keck R, Presta LG, Frenz J. Isomerization of an aspartic acid residue in the complementarity-determining regions of a recombinant antibody to human IgE: identification and effect on binding affinity. Biochemistry. 1996;35(6):1897-903. doi:10.1021/bi951526c. PMID:8639672
  • Kueltzo LA, Wang W, Randolph TW, Carpenter JF. Effects of solution conditions, processing parameters, and container materials on aggregation of a monoclonal antibody during freeze-thawing. J Pharm Sci. 2008;97(5):1801-12. doi:10.1002/jps.21110. PMID:17823949
  • Brych SR, Gokarn YR, Hultgen H, Stevenson RJ, Rajan R, Matsumura M. Characterization of antibody aggregation: role of buried, unpaired cysteines in particle formation. J Pharm Sci. 2010;99(2):764-81. doi:10.1002/jps.21868. PMID:19691118
  • Ghazvini S, Kalonia C, Volkin DB, Dhar P. Evaluating the role of the air-solution interface on the mechanism of subvisible particle formation caused by mechanical agitation for an IgG1 mAb. J Pharm Sci. 2016;105(5):1643-56. doi:10.1016/j.xphs.2016.02.027. PMID:27025981
  • Kiese S, Papppenberger A, Friess W, Mahler HC. Shaken, not stirred: mechanical stress testing of an IgG1 antibody. J Pharm Sci. 2008;97(10):4347-66. doi:10.1002/jps.21328. PMID:18240293
  • Mahler HC, Muller R, Friess W, Delille A, Matheus S. Induction and analysis of aggregates in a liquid IgG1-antibody formulation. Eur J Pharm Biopharm. 2005;59(3):407-17. doi:10.1016/j.ejpb.2004.12.004. PMID:15760721
  • Serno T, Carpenter JF, Randolph TW, Winter G. Inhibition of agitation-induced aggregation of an IgG-antibody by hydroxypropyl-beta-cyclodextrin. J Pharm Sci. 2010;99(3):1193-1206. doi:10.1002/jps.21931. PMID:19774651
  • Huh JH, White AJ, Brych SR, Franey H, Matsumura M. The identification of free cysteine residues within antibodies and a potential role for free cysteine residues in covalent aggregation because of agitation stress. J Pharm Sci. 2013;102(6):1701-11. doi:10.1002/jps.23505. PMID:23559428
  • Brady LJ, Martinez T, Balland A. Characterization of nonenzymatic glycation on a monoclonal antibody. Anal Chem. 2007;79(24):9403-13. doi:10.1021/ac7017469. PMID:17985928
  • Eppler A., Weigandt M., Hanefeld A., Bunjes H. Relevant shaking stress conditions for antibody preformulation development. Eur J Pharm Biopharm. 2010;74(2):139-47. doi:10.1016/j.ejpb.2009.11.005. PMID:19922795
  • Sharma DK, Oma P, Pollo MJ, Sukumar, M. Quantification and characterization of subvisible proteinaceous particles in opalescent mAb formulations using micro-flow imaging. J Pharm Sci. 2010;99(6):2628-42. doi:10.1002/jps.22046. PMID:20049937
  • Arosio P, Rima S, Morbidelli M. Aggregation mechanism of an IgG2 and two IgG1 monoclonal antibodies at low pH: from oligomers to larger aggregates. Pharm Res. 2013;30(3):641-54. doi:10.1007/s11095-012-0885-3. PMID:23054090
  • Cohen SL, Price C, Vlasak J. Beta-elimination and peptide bond hydrolysis: two distinct mechanisms of human IgG1 hinge fragmentation upon storage. J Am Chem Soc. 2007;129(22):6976-77. doi:10.1021/ja0705994. PMID:17500521
  • Nowak C, Ponniah G, Neill A, Liu H. Characterization of succinimide stability during trypsin digestion for LC-MS analysis. Anal Biochem. 2017;526:1-8. doi:10.1016/j.ab.2017.03.005. PMID:28274724
  • Liu YD, van Enk JZ, Flynn, GC. Human antibody Fc deamidation in vivo. Biologicals. 2009;37(5):313-22. doi:10.1016/j.biologicals.2009.06.001. PMID:19608432
  • Wang L, Amphlett G, Lambert JM, Blattler W, Zhang W. Structural characterization of a recombinant monoclonal antibody by electrospray time-of-flight mass spectrometry. Pharm Res. 2005;22(8):1338-49. doi:10.1007/s11095-005-5267-7. PMID:16078144
  • Chelius D, Rehder DS, Bondarenko PV. Identification and characterization of deamidation sites in the conserved regions of human immunoglobulin gamma antibodies. Anal Chem. 2005;77(18):6004-11. doi:10.1021/ac050672d. PMID:16159134
  • Sinha S, Zhang L, Duan S, Williams TD, Vlasak J, Ionescu R, Top, EM. Effect of protein structure on deamidation rate in the Fc fragment of an IgG1 monoclonal antibody. Protein Sci. 2009;18(8):1573-84. doi:10.1002/pro.173. PMID:19544580
  • Huang L, Lu J, Wroblewski VJ, Beals JM, Riggin RM. In vivo deamidation characterization of monoclonal antibody by LC/MS/MS. Anal Chem. 2005;77(5):1432-39. doi:10.1021/ac0494174. PMID:15732928
  • Harris RJ, Kabakoff B, Macch FD, Shen FJ, Kwong M, Andya JD, Shire SJ, Bjork N, Totpal K, Chen AB. Identification of multiple sources of charge heterogeneity in a recombinant antibody. J Chromatogr B Biomed Sci Appl. 2001;752(2):233-45. doi:10.1016/S0378-4347(00)00548-X. PMID:11270864
  • Vlasak J, Bussat MC, Wang S, Wagner-Rousset E, Schaefer M, Klinguer-Hamour C, Kirchmeier M, Corvaia N, Ionescu R, Beck A. Identification and characterization of asparagine deamidation in the light chain CDR1 of a humanized IgG1 antibody. Anal Biochem. 2009;392(2):145-54. doi:10.1016/j.ab.2009.05.043. PMID:19497295
  • Creed D. The photophysics and photochemistry of the near-UV absorbing amino acids-I, Tryptophan and its simple derivatives. Photochem Photobiol. 1984;39(4):537-62. doi:10.1111/j.1751-1097.1984.tb03890.x
  • Holt LA, Milligan B, Rivett DE, Stewart FH. The photodecomposition of tryptophan peptides. Biochim Biophys Acta. 1977;499(1):131-38. doi:10.1016/0304-4165(77)90235-5. PMID:889893
  • Kerwin BA, Remmele RL, Jr. Protect from light: photodegradation and protein biologics. J Pharm Sci. 2007;96(6):1468-79. doi:10.1002/jps.20815. PMID:17230445
  • Singh SR, Zhang J, O'Dell C, Hsieh MC, Goldstein J, Liu J, Srivastava A. Effect of polysorbate 80 quality on photostability of a monoclonal antibody. AAPS PharmSciTech. 2012;13(2):422-30. doi:10.1208/s12249-012-9759-6. PMID:22362139
  • Qi P, Volkin DB, Zhao H, Nedved ML, Hughes R, Bass R, Yi SC, Panek ME, Wang D, Dalmonte P, et al. Characterization of the photodegradation of a human IgG1 monoclonal antibody formulated as a high-concentration liquid dosage form. J Pharm Sci. 2009;98(9):3117-30. doi:10.1002/jps.21617. PMID:19009595
  • Nowak C, Ponniah G, Cheng G, Kita A, Neill A, Kori Y, Liu H. Liquid chromatography-fluorescence and liquid chromatography-mass spectrometry detection of tryptophan degradation products of a recombinant monoclonal antibody. Anal Biochem. 2016;496:4-8. doi:10.1016/j.ab.2015.12.004. PMID:26717898
  • Wei Z, Feng J., Lin HY, Mullapudi S, Bishop E, Tous GI, Casas-Finet J, Hakki F, Strouse R, Schenerman MA. Identification of a single tryptophan residue as critical for binding activity in a humanized monoclonal antibody against respiratory syncytial virus. Anal Chem. 2007;79(7):2797-2805. doi:10.1021/ac062311j. PMID:17319649
  • Liu H, Gaza-Bulseco G, Zhou L. Mass spectrometry analysis of photo-induced methionine oxidation of a recombinant human monoclonal antibody. J Am Soc Mass Spectrom. 2009;20(3):525-28. doi:10.1016/j.jasms.2008.11.011. PMID:19103498
  • Li Y, Polozova A, Gruia F, Feng J. Characterization of the degradation products of a color-changed monoclonal antibody: tryptophan-derived chromophores. Anal Chem. 2014;86(14):6850-57. doi:10.1021/ac404218t. PMID:24937252
  • Reubsaet JL, Beijnen JH, Bult A, van Maanen RJ, Marchal JA, Underberg WJ. Analytical techniques used to study the degradation of proteins and peptides: chemical instability. J Pharm Biomed Anal. 1998;17(6–7):955-78. doi:10.1016/S0731-7085(98)00063-6. PMID:9884187
  • Chumsae C, Gaza-Bulseco G, Sun J, Liu H. Comparison of methionine oxidation in thermal stability and chemically stressed samples of a fully human monoclonal antibody. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;850(1–2):285-94. doi:10.1016/j.jchromb.2006.11.050. PMID:17182291
  • Valliere-Douglass JF, Connell-Crowley L, Jensen R, Schnier PD, Trilisky E, Leith M, Follstad B D, Kerr J, Lewis N, Vunnum S, et al. Photochemical degradation of citrate buffers leads to covalent acetonation of recombinant protein therapeutics. Protein Sci. 2010;19(11):2152-63. doi:10.1002/pro.495. PMID:20836085
  • Keck RG The use of t-butyl hydroperoxide as a probe for methionine oxidation in proteins. Anal Biochem. 1996;236(1):56-62. doi:10.1006/abio.1996.0131. PMID:8619496
  • Folzer E, Diepold K, Bomans K, Finkler C, Schmidt R, Bulau P, Huwyler J, Mahler HC, Koulov AV. Selective oxidation of methionine and tryptophan residues in a therapeutic igg1 molecule. J Pharm Sci. 2015;104(9):2824-31. doi:10.1002/jps.24509. PMID:26010344
  • Ma Y, Chao C, Stadtman ER. Oxidative modification of glutamine synthetase by 2,2′-Azobis(2-amidinopropane) dihydrochloride. Arch Biochem Biophys. 1999;363(1):129-34. doi:10.1006/abbi.1998.1076. PMID:10049507
  • Bertolotti-Ciarlet A, Wang W, Lownes R, Pristatsky P, Fang Y, McKelvey T, Li Y, Li Y, Drummond J, Prueksaritanont T, Vlasak J. Impact of methionine oxidation on the binding of human IgG1 to Fc Rn and Fc gamma receptors. Mol Immunol. 2009;46(8–9):1878-82. doi:10.1016/j.molimm.2009.02.002. PMID:19269032
  • Pan H, Chen K, Chu L, Kinderman F, Apostol I, Huang G. Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn. Protein Sci. 2009;18(2):424-33. doi:10.1002/pro.45. PMID:19165723
  • Wang W, Vlasak J, Li Y, Pristatsky P, Fang Y, Pittman T, Roman J, Wang Y, Prueksaritanont T, Ionescu R. Impact of methionine oxidation in human IgG1 Fc on serum half-life of monoclonal antibodies. Mol Immunol. 2011;48(6–7):860-66. doi:10.1016/j.molimm.2010.12.009. PMID:21256596
  • Yang R, Jain T, Nobrega RP, Lu X, Boland T, Burnina I, Sun T, Caffry I, Brown M, Zhi X, et al. Rapid assessment of oxidation via middle-down LCMS correlates with methionine side-chain solvent-accessible surface area for 121 clinical stage monoclonal antibodies. MAbs. 2017;9(4):646-53. doi:10.1080/19420862.2017.1290753
  • Liu D, Ren D, Huang H, Dankberg J, Rosenfeld R, Cocco MJ, Li L, Brems DN, Remmele RL, Jr. Structure and stability changes of human IgG1 Fc as a consequence of methionine oxidation. Biochemistry. 2008;47(18):5088-5100. doi:10.1021/bi702238b. PMID:18407665
  • Yan B, Yates Z, Balland A, Kleemann GR. Human IgG1 hinge fragmentation as the result of H2O2-mediated radical cleavage. J Biol Chem. 2009;284(51):35390-402. doi:10.1074/jbc.M109.064147. PMID:19850927
  • Goetze AM, Liu YD, Arroll T, Chu L, Flynn GC. Rates and impact of human antibody glycation in vivo. Glycobiology. 2012;22(2):221-34. doi:10.1093/glycob/cwr141. PMID:21930650
  • Gadgil HS, Bondarenko PV, Pipes G, Rehder D, McAuley A, Perico N, Dillon T, Ricci M, Treuheit M. The LC/MS analysis of glycation of IgG molecules in sucrose containing formulations. J Pharm Sci. 2007;96(10):2607-21. doi:10.1002/jps.20966. PMID:17621682
  • Quan C, Alcala E, Petkovska I, Matthews D, Canova-Davis E, Taticek R, Ma S. A study in glycation of a therapeutic recombinant humanized monoclonal antibody: where it is, how it got there, and how it affects charge-based behavior. Anal Biochem. 2008;373(2):179-91. doi:10.1016/j.ab.2007.09.027. PMID:18158144
  • Zhang B, Yang Y, Yuk I, Pai R, McKay P, Eigenbrot C, Dennis M, Katta V, Francissen K C. Unveiling a glycation hot spot in a recombinant humanized monoclonal antibody. Anal Chem. 2008;80(7):2379-90. doi:10.1021/ac701810q. PMID:18307322
  • Butko M, Pallat H, Cordoba A, Yu XC Recombinant antibody color resulting from advanced glycation end product modifications. Anal Chem. 2014;86(19):9816-23. doi:10.1021/ac5024099. PMID:25181536
  • Miller AK, Hambly DM, Kerwin BA, Treuheit MJ, Gadgil HS. Characterization of site-specific glycation during process development of a human therapeutic monoclonal antibody. J Pharm Sci. 2011;100(7):2543-50. doi:10.1002/jps.22504. PMID:21287557
  • Yuk IH, Zhang B, Yang Y, Dutina G, Leach KD, Vijayasankaran N, Shen AY, Andersen DC, Snedecor BR, Joly JC. Controlling glycation of recombinant antibody in fed-batch cell cultures. Biotechnol Bioeng. 2011;108(11):2600-10. doi:10.1002/bit.23218. PMID:21618472
  • Fischer S, Hoernschemeyer J, Mahler H C. Glycation during storage and administration of monoclonal antibody formulations. Eur J Pharm. Biopharm. 2008;70(1):42-50. doi:10.1016/j.ejpb.2008.04.021. PMID:18583113
  • Beck A, Wurch T, Bailly C, Corvaia N. Strategies and challenges for the next generation of therapeutic antibodies. Nat Rev Immunol. 2010;10(5):345-52. doi:10.1038/nri2747. PMID:20414207
  • Yang X, Xu W, Dukleska S, Benchaar S, Mengisen S, Antochshuk V, Cheung J, Mann L, Babadjanova Z, Rowand J, et al. Developability studies before initiation of process development: improving manufacturability of monoclonal antibodies. MAbs. 2013;5(5):787-94. doi:10.4161/mabs.25269. PMID:23883920
  • Jarasch A, Koll H, Regula JT, Bader M, Papadimitriou A, Kettenberger H. Developability assessment during the selection of novel therapeutic antibodies. J Pharm Sci. 2015;104(6):1885-98. doi:10.1002/jps.24430. PMID:25821140
  • Liu H, Ponniah G, Zhang HM, Nowak C, Neill A, Gonzalez-Lopez N, Patel R, Cheng G, Kita AZ, Andrien B. In vitro and in vivo modifications of recombinant and human IgG antibodies. MAbs. 2014;6(5):1145-54. doi:10.4161/mabs.29883. PMID:25517300
  • Rizzo JM, Shi S, Li Y, Semple A, Esposito JJ, Yu S, Richardson D, Antochshuk V, Shameem M. Application of a high-throughput relative chemical stability assay to screen therapeutic protein formulations by assessment of conformational stability and correlation to aggregation propensity. J Pharm Sci. 2015;104(5):1632-40. doi:10.1002/jps.24408. PMID:25757872
  • Wang T, Kumru OS, Yi L., Wang YJ., Zhang J., Kim JH., Joshi SB., Middaugh CR., Volkin D B. Effect of ionic strength and pH on the physical and chemical stability of a monoclonal antibody antigen-binding fragment. J Pharm Sci. 2013;102(8):2520-37. doi:10.1002/jps.23645. PMID:23824562
  • Liu H, Gaza-Bulseco G, Faldu D, Chumsae C, Sun J. Heterogeneity of monoclonal antibodies. J Pharm Sci. 2008;97(7):2426-47. doi:10.1002/jps.21180. PMID:17828757
  • Ponniah G, Kita A, Nowak C, Neill A, Kori Y, Rajendran S, Liu H. Characterization of the acidic species of a monoclonal antibody using weak cation exchange chromatography and LC-MS. Anal Chem. 2015;87(17):9084-92. doi:10.1021/acs.analchem.5b02385
  • Alt N, Zhang TY, Motchnik P, Taticek R, Quarmby V, Schlothauer T, Beck H, Emrich T, Harris RJ. Determination of critical quality attributes for monoclonal antibodies using quality by design principles. Biologicals. 2016;44(5):291-305. doi:10.1016/j.biologicals.2016.06.005. PMID:27461239
  • Haberger M, Bomans K, Diepold K, Hook M, Gassner J, Schlothauer T, Zwick A, Spick C, Kepert JF, Hienz B, et al. Assessment of chemical modifications of sites in the CDRs of recombinant antibodies: Susceptibility vs. functionality of critical quality attributes. MAbs. 2014;6(2):327-39. doi:10.4161/mabs.27876. PMID:24441081
  • Pisupati K, Benet A, Tian Y, Okbazghi S, Kang J, Ford M, Saveliev S, Sen KI, Carlson E, Tolbert TJ, et al. Biosimilarity under stress: a forced degradation study of Remicade® and Remsima™. MAbs. 2017;9(7): in press.

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