Establishment of System Suitability Standard for N-glycan Profile Analysis of Monoclonal Antibodies
WANG Wen-bo, WU Gang, YU Chuan-fei, ZHANG Feng, WANG Lan*
Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing 102629, China
Abstract：OBJECTIVE To establish the system suitability standard for N-glycan profile analysis of monoclonal antibodies. METHODS LC-MS was used to characterize the N-linked glycoform of the system suitability standard, and the stability was evaluated. The acceptance criteria of system suitability was set according to the method property and the data from method validation. RESULTS The data of accelerated and long-term stability test indicated that the system suitability standard was stable under storage condition. The N-glycoform of this standard was representative, which covered the main glycoform of monoclonal antibodies. The acceptance criteria of system suitability set for the three analytical METHODS were as below: the detected chromatogram should be visually similar to representative chromatogram; the resolution between G1F(1, 6) and G1F(1, 3), and G0F percentage should meet the specific requirements; the RSD of G0F retention time should be ≤4%. CONCLUSION The standard substance for system suitability test and acceptance criteria for three N-glycan profile analytical METHODS are established.
王文波, 武刚, 于传飞, 张峰, 王兰. 单抗N糖分析系统适用性对照品的建立[J]. 中国药学杂志, 2020, 55(4): 317-321.
WANG Wen-bo, WU Gang, YU Chuan-fei, ZHANG Feng, WANG Lan. Establishment of System Suitability Standard for N-glycan Profile Analysis of Monoclonal Antibodies. Chinese Pharmaceutical Journal, 2020, 55(4): 317-321.
GOETZE A M, SCHENAUER M R, FLYNN G C. Assessing monoclonal antibody product quality attribute criticality through clinical studies [J]. mAbs, 2010, 2(5): 500-507.
[2]
LONARDO A, SAXENA PAREKH B, SRIVASTAVA A. Bio-CoDa: a new analysis class to ensure accurate and precise monoclonal antibody CQA estimation and control [J]. Biotechnol Bioeng, 2017, 114(9): 2001-2010.
[3]
BRISCOE C J, STILES M R, HAGE D S. System suitability in bioanalytical LC-MS/MS [J]. J Pharm Biomed Anal, 2007, 44(2):484-491.
[4]
COLEMAN J, WRZOSEK T, ROMAN R, et al. Setting system suitability criteria for detectability in high-performance liquid chromatography methods using signal-to-noise ratio statistical tolerance intervals [J]. J Chromatogr A, 2001, 917(1-2):23-27.
[5]
HUND E, VANDER HEYDEN Y, MASSART D L, et al. Derivation of system suitability test limits from a robustness test on an LC assay with complex antibiotic samples [J]. J Pharm Biomed Anal, 2002, 30(4):1197-1206.
[6]
KAMINSKI L, DEGENHARDT M, ERMER J, et al. Efficient and economic HPLC performance qualification [J]. J Pharm Biomed Anal, 2010, 51(3):557-564.
[7]
MATEJTSCHUK P, DURU C, BRISTOW A F, et al. Establishment of an erythropoietin CRS with stable measurable dimer content for SEC system suitability qualification [J]. Pharmeur Bio Sci Notes, 2019,(2019):11-26.
[8]
LIU H, NOWAK C, ANDRIEN B, et al. Impact of IgG Fc-Oligosaccharides on recombinant monoclonal antibody structure, stability, safety, and efficacy [J]. Biotechnol Prog, 2017, 33(5):1173-1181.
[9]
RAJU T S. Terminal sugars of Fc glycans influence antibody effector functions of IgGs [J]. Curr Opin Immunol, 2008, 20(4):471-478.
[10]
SZIGETI M, CHAPMAN J, BORZA B, et al. Quantitative assessment of mAb Fc glycosylation of CQA importance by capillary electrophoresis [J]. Electrophoresis, 2018, 39(18):2340-2343.
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