Red colored IgG4 caused by vitamin B12from cell culture media combined with disulfide reduction at harvest

mAbs

Volumn 6, Issue 3, 2014, Pages 679-688

  Derfus, Gayle E ^a   Dizon Maspat, Jemelle ^a   Broddrick, Jared T ^a   Velayo, Arleene C ^a   Toschi, Josh D ^a   Santuray, Rodell T ^a   Hsu, Stephen K ^a   Winter, Charles M ^a   Krishnan, Rajesh ^a   Amanullah, Ashraf ^a  

^a Biologics Development   (United States)

Author keywords

Bioprocess; Chinese hamster ovary; Color; High concentration; Monoclonal antibody

Indexed keywords

COBALT; CYANOCOBALAMIN; DISULFIDE; HYDROXOCOBALAMIN; IMMUNOGLOBULIN G4; CULTURE MEDIUM; IMMUNOGLOBULIN G; MONOCLONAL ANTIBODY;

ALKYLATION; ANALYTIC METHOD; ANIMAL CELL; ANIMAL EXPERIMENT; ANTIBODY BLOOD LEVEL; ARTICLE; CELL CULTURE; CHEMICAL REACTION; COLOR; EXPERIMENTAL MODEL; HARVEST; HUMAN; LIGHT EXPOSURE; NONHUMAN; ANIMAL; CHEMISTRY; CHO CELL LINE; COLORIMETRY; CRICETULUS; CULTURE MEDIUM; ISOLATION AND PURIFICATION; LIGHT; MEDICINAL CHEMISTRY; OXIDATION REDUCTION REACTION;

ANIMALS; ANTIBODIES, MONOCLONAL; CHEMISTRY, PHARMACEUTICAL; CHO CELLS; COBALT; COLOR; COLORIMETRY; CRICETULUS; CULTURE MEDIA; DISULFIDES; HUMANS; IMMUNOGLOBULIN G; LIGHT; OXIDATION-REDUCTION; VITAMIN B 12;

EID: 84899768673     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.4161/mabs.28257     Document Type: Article

References (16)

1. Shire SJ, Shahrokh Z, Liu J. Challenges in the development of high protein concentration formulations. J Pharm Sci 2004; 93:1390-402; PMID:15124199; http://dx.doi.org/10.1002/jps.20079
2. Neergaard MS, Kalonia DS, Parshad H, Nielsen AD, Møller EH, van de Weert M. Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - prediction of viscosity through protein-protein interaction measurements. Eur J Pharm Sci 2013; 49:400-10; PMID:23624326; http://dx.doi.org/10.1016/j.ejps.2013.04.019
3. Parenteral Drug Association. PDA comments: ICH Q6A; draft guidance on specifications. PDA J Pharm Sci Technol 1998; 52:232-3; PMID:9846071
4. Vijayasankaran N, Varma S, Yang Y, Mun M, Arevalo S, Gawlitzek M, Swartz T, Lim A, Li F, Zhang B, et al. Effect of cell culture medium components on color of formulated monoclonal antibody drug substance. Biotechnol Prog 2013; In press; http://dx.doi.org/10.1002/btpr.1772.
5. Zhu X, Wentworth P Jr., Kyle RA, Lerner RA, Wilson IA. Cofactor-containing antibodies: crystal structure of the original yellow antibody. Proc Natl Acad Sci U S A 2006; 103:3581-5; PMID:16537445; http://dx.doi.org/10.1073/pnas.0600251103
6. Color ASL. United States Food and Drug Administration, 2009. http://www.fda.gov/forindustry/coloradditives /coloradditiveinventories/ ucm115641.htm
7. Pamidi PV, DeAbreu M, Kim D, Mansouri S. Hydroxocobalamin and cyanocobalamin interference on co-oximetry based hemoglobin measurements. Clin Chim Acta 2009; 401:63-7; PMID:19041637; http://dx.doi.org/10.1016/j.cca.2008. 11.007
8. Gagnon P. Production of Biobetter IgG wtih Enhanced Wash and Elution of Protein A. BIT 2nd International Congress of Antibodies. Beijing, China, 2010.
9. Trexler-Schmidt M, Sargis S, Chiu J, Sze-Khoo S, Mun M, Kao YH, Laird MW. Identification and prevention of antibody disulfide bond reduction during cell culture manufacturing. Biotechnol Bioeng 2010; 106:452-61; PMID:20178122
10. Kao YH, Hewitt DP, Trexler-Schmidt M, Laird MW. Mechanism of antibody reduction in cell culture production processes. Biotechnol Bioeng 2010; 107:622-32; PMID:20589844; http://dx.doi.org/10.1002/bit.22848
11. Schwertner HA, Valtier S, Bebarta VS. Liquid chromatographic mass spectrometric (LC/MS/MS) determination of plasma hydroxocobalamin and cyanocobalamin concentrations after hydroxocobalamin antidote treatment for cyanide poisoning. J Chromatogr B Analyt Technol Biomed Life Sci 2012; 905:10-6; PMID:22939270; http://dx.doi.org/10.1016/j.jchromb.2012.07.012
12. Juzeniene A, Nizauskaite Z. Photodegradation of cobalamins in aqueous solutions and in human blood. J Photochem Photobiol B 2013; 122:7-14; PMID:23558034; http://dx.doi.org/10.1016/j.jphotobiol.2013.03.001
13. Prentice KM, Gillespie R, Lewis N, Fujimori K, McCoy R, Bach J, Connell-Crowley L, Eakin CM. Hydroxocobalamin association during cell culture results in pink therapeutic proteins. MAbs 2013; 5:972-9; PMID:23924851; http://dx.doi.org/10.4161/mabs.25921
14. Adler N, Medwick T, Poznanski T. Reaction of hydroxocobalamin with thiols. J Am Chem Soc 1966; 88:5018-20; http://dx.doi.org/10.1021/ja00973a044
15. HunterLab. The Basics of Color Perception and Measurement. 2001. www.elscolab.nl/pdf/color.pdf
16. 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; 83:5912-9; PMID:21692515; http://dx.doi.org/10.1021/ac200750u