Method Validation of Methodology Similarity between Rituximab and Its Biosimilar by ELISA
WANG Meng-jia1, DONG Li-hou2, LI Wan-wan3, LÜ Xiao-long3, WANG Bian-zhen3*, GE Zhi-qiang1*
1. School of Chemical Engineering and Technology, Tianjing University, Tianjin 300072, China; 2. Institute of Military Medicine, Academy of Military Sciences, Beijing 102206, China; 3. United-Power Pharma Tech Co., Ltd., Beijing 102206, China
Abstract:OBJECTIVE To validate the methodology similarity of the biosimilar (recombinant anti-human CD20 chimeric monoclonal antibody, B) and the reference (rituximab, R). METHODS The biosimilar and the reference were measured by a sandwich enzyme-linked immunosorbent assay (ELISA), and the concentration of the analytes were back-calculated with Watson LIMSTM V.7.3.0.01 (Thermo Scientific Inc.). The comparison of similarity between B and T were investigated with a balanced experiment design, and the results of the standard curves were evaluated with a statistic method, square of sum, using the statistic tool, Allfit. Systematic validation of the method from accuracy, precision, specificity, sensitivity, selectivity, dilution linearity, and stability etc. aspects. RESULTS The results of the standard curves from the balanced designed experiments of the biosimilar and the reference were compared, and the statistical result was P=0.050 7, which showed no significant statistic difference (P>0.05). The systematic validation results showed that the intra-assay accuracy and precision of the method between the biosimilar and the reference were within the range of 5.6%-7.7% and -9.0%--0.8%, respectively; the inter-assay accuracy and precision of the method between the B and the T were within the range of 6.5%-7.2% and -7.3%--3.2%, respectively; the total error of the method was not more than 13.9%, which met the methodological acceptance criteria. The results of selectivity, specificity, dilution linearity, and stability were within the acceptance criteria. CONCLUSION The ELISA method, which was systematically validated with the balanced experimental design meets the acceptance criteria of biosimilar methodology requirement, and could be used to support the pharmacokinetic study of rituximab and its biosimilar.
王梦佳, 董立厚, 李弯弯, 吕晓龙, 王变珍, 葛志强. 运用ELISA对利妥昔单抗及其生物类似药在方法学上进行相似性验证[J]. 中国药学杂志, 2020, 55(19): 1622-1628.
WANG Meng-jia, DONG Li-hou, LI Wan-wan, LÜ Xiao-long, WANG Bian-zhen, GE Zhi-qiang. Method Validation of Methodology Similarity between Rituximab and Its Biosimilar by ELISA. Chinese Pharmaceutical Journal, 2020, 55(19): 1622-1628.
CFDA. Guideline on Development and Evaluation of Biosimilars ( 2015) . 2015.
[2]
EMA. Guideline on similar biological medicinal products. . (2005-10-30). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/-09/WC500003517.pdf.
[3]
GAO C Y, XIE S M, BAI Y, et al. VConsiderations on clinical study of biosimilars. Chin Pharm J(中国药学杂志), 2015,50(6):494-496.
[4]
LIU B N, BAI Y, LUO J H. Biosimilarity study regarding product quality of candidate monoclonal antibodies as biosimilars. Chin Pharm J(中国药学杂志), 2017, 52(13):1194-1200.
[5]
WHO. Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs). . (2009-10). http://www.who int/biologicals/areas/biological_therepeutics/BIOTHERA-PEUTICS_TOR_WEB_22APRIL2010.pdf.
[6]
FDA. Scientific considerations in demonstrating biosimilarity to a reference product. . (2015-04) . https://www.fda.gov/downloads/ drugs/guidance compliance regulat-ory information/guidances/ucm 291128.pdf.
[7]
EMA. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1) (EMA/CHMP/BWP/247713/2012) . (2015-04). . http://www. ema. europa. eu/docs/en_GB/document_librar-y/Scientific_guideline/2014/06/WC500167838. pdf.
[8]
US Food and Drugs Administration. Scientific considerations in demonstrating biosimilarity to a reference product: Guidance for industry . 2015. https://www.fda.g-ov/downloads/ drugs/guidances/ucm291128.pdf. Accessed 31May2018.
[9]
ANTONIA M S MÜLLER, IHORST G, MERTELSMANN R, et al. Epidemiology of non-Hodgkin′s lymphoma (NHL):trends, geographic distribution, and etiology. Ann Hematol, 2005, 84(1):1-12.
[10]
HALLEK, MICHAEL. Chronic lymphocytic leukemia: 2013 update on diagnosis, risk stratification and treatment. Am J Hematol, 2013, 88(9):803-816.
[11]
BANCHEREAU J. Human B lymphocytes: phenotype, proliferation, and differentiation. Adv Immunol, 1992, 52:125-262.
[12]
MALONEY D G. Anti-CD20 antibody therapy for B-cell lymphomas. N Engl J Med, 2012, 366:2008-2016.
[13]
ZELENETZ A D, GORDON L I, ABRAMSON, et al. NCCN guidelines insights: B-cell lymphomas, version 3.2019. J Natl Comprehensive Cancer Network, 2019, 17(6):650-661.
[14]
DREYLING M, GHIELMINI M, RULE S, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2016, 27(15):83-90.
[15]
International Pharmaceutical Regulators Forum Biosimilars working Group. Reflection paper on extrapolation of indications in authorization of biosimilar products version1. 3 . (2016). . www.i-p-r-f.org/files/1614/7315/4963/160725 IPRF BWG Reflection paper final draftver 1.3 IPRF MC Circulation.pdf.
[16]
MARINI J C, ANDERSON M, CAI X Y, et al. Systematic verification of bioanalytical similarity between a biosimilar and a reference biotherapeutic: committee recommendations for the development and validation of a single ligand-binding assay to support pharmacokinetic assessments. AAPS, 2014, 16(6):1149-1158.
[17]
FDA. Assay development and validation for immunogenicity testing of therapeutic protein products. . April 2016. https://www.fda.gov.
[18]
UNITED STATES PHARMACOPEIA. Immunogenicity assays-design and validation of immunoassays to detect antidrug neutralizing antibody. . http://www.usp.org.
[19]
SHANKAR G, DEVANARAYAN V, AMARAVADI L, et al. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. J Pharm Biomed Anal, 2008, 48(5):1267-1281.
[20]
GUPTA S, DEVANARAYAN V, FINCO D, et al. Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics. J Pharm Biomed Anal, 2011, 55(5):878-888.
[21]
EMEA/CHMP/BMWP/14327/2006 Rev.1Guideline on immunogenicity assessment of biotechnology-derived therapeutic Proteins. . . https://www.ema.europa.eu/en/documents/scientific-guideline
[22]
DESILVA B, SMITH W, WEINER R, et al. Recommendations for the bioanalytical method validation of ligand-binding assays to support pharmacokinetic assessments of macromolecules. Pharm Res, 2003, 20(11):1885-1900.
[23]
CAI X Y, GOUTY D, BAUGHMAN S, et al. Recommendations and requirements for the design of bioanalytical testing used in comparability studies for biosimilar drug development. Bioanalysis, 2011, 3(5):535-540.