biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Productsbiopreparat-63Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESТест-система для определения наличия связывающих антител к интерферону бета-1а для клинического примененияTest system for the detection of binding antibodies to interferon beta-1a for clinical useКузьминоваЕ. А.KuzminovaE. A.

Старший научный сотрудник лаборатории иммунологических методов отдела доклинических испытаний лекарственных средств

Senior researcher of the laboratory of immunological methods of the Department of preclinical trials drug products

biocad@biocad.ruОстроуховаТ. Ю.OstroukhovaT. Yu.

Руководитель лаборатории иммунологических методов отдела доклинических испытаний лекарственных средств, канд. биол. наук

Head of the laboratory of immunological methods of the Department of preclinical trials of drug products. Candidate of Biological Sciences

noemail@neicon.ruГрачевА. В.GrachevA. V.

Старший научный сотрудник отдела иммунохимии

Senior researcher of the Department of immunochemistry

noemail@neicon.ruМорозоваЕ. Л.MorozovaE. L.

Руководитель отдела доклинических испытаний лекарственных средств

Head of the Department of preclinical trials of drug products

noemail@neicon.ruЗАО «БИОКАД»РоссияCJSC «BIOCAD»Russian Federation201620022018163182188Copyright © Кузьминова Е.А., Остроухова Т.Ю., Грачев А.В., Морозова Е.Л., 20182018Кузьминова Е.А., Остроухова Т.Ю., Грачев А.В., Морозова Е.Л.Kuzminova E.A., Ostroukhova T.Y., Grachev A.V., Morozova E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.biopreparations.ru/jour/article/view/63

Разработана тест-система для определения наличия связывающих антител к интерферону бета 1а (САт к ИФН бета-1а) в сыворотке крови человека с использованием метода твердофазного иммуноферментного анализа. С целью описания характеристик тест-системы проведены валидационные мероприятия, включающие исследование чувствительности, селективности, специфичности, прецизионности и точности, робастности, стабильности, пригодности тест-системы. Показана применимость данной тест-системы для использования в рамках клинических исследований - оценка иммуногенности препаратов интерферона бета-1а (пегилированных и непегилированных форм).

Test system for determining the presence of binding antibodies to interferon beta-1a (BAB to IFN beta-1a) in serum using ELISA has been developed. The validation included sensitivity, selectivity, specificity, precision and accuracy, robustness, stability, suitability of the test system studies. The applicability of the mentioned test system has been approved for the use in clinical studies for the evaluation of interferon beta-1a immunogenicity (pegylated and non-pegylated forms).

интерферон бета 1аиммуногенностьтвердофазный иммуноферментный анализ (ИФА)связывающие антитела (САт)антитела к препаратурассеянный склерозбиоаналитические методы исследованияклинические исследованияinterferon beta-1aimmunogenicityenzyme linked immunosorbent assay (ELISA)binding antibodies (BAB)anti-drug antibodies (ADAs)multiple sclerosis (MS)bioanalytical methodsclinical studiesReferencesBarnard JG, Babcock K, Carpenter JF. Characterization and quantitation of aggregates and particles in interferon-β products: potential links between product quality attributes and immunogenicity. Journal of Pharmaceutical Sciences 2013; 102(3): 915-28.Barnard JG, Babcock K, Carpenter JF. Characterization and quantitation of aggregates and particles in interferon-â products: potential links between product quality attributes and immunogenicity. Journal of Pharmaceutical Sciences 2013; 102(3): 915–28.Mastrangeli R, Rossi M, Mascia M, Palinsky W, Datola A, Terlizzese M, Bierau H. In vitro biological characterization of IFN-β-1a major glycoforms. Glycobiology 2015; 25(1): 21-9.Mastrangeli R, Rossi M, Mascia M, Palinsky W, Datola A, Terlizzese M, Bierau H. In vitro biological characterization of IFN-â-1a major glycoforms. Glycobiology 2015; 25(1): 21–9.Ahn SH, Lee HW, Kim YS, Kim JK, Han KH, Chon CY, Moon YM. Recombinant interferon-Beta-1alpha plus ribavirin for the treatment of chronic HCV infection: a prospective, randomized, comparative pilot study. Gut Liver 2009; 3(1): 20-5.Ahn SH, Lee HW, Kim YS, Kim JK, Han KH, Chon CY, Moon YM. Recombinant interferon-Beta-1alpha plus ribavirin for the treatment of chronic HCV infection: a prospective, randomized, comparative pilot study. Gut Liver 2009; 3(1): 20–5.Zare N, Zarkesh-Esfahani SH, Gharagozloo M, Shaygannejad V. Antibodies to interferon beta in patients with multiple sclerosis receiving CinnoVex, rebif, and betaferon. Journal of Korean Medical Science 2013; 28(12): 1801-6.Zare N, Zarkesh-Esfahani SH, Gharagozloo M, Shaygannejad V. Antibodies to interferon beta in patients with multiple sclerosis receiving CinnoVex, rebif, and betaferon. Journal of Korean Medical Science 2013; 28(12): 1801–6.Gneiss C, Tripp P, Reichartseder F, Egg R, Ehling R, Lutterotti A, Khalil M, Kuenz B, Mayringer I, Reindl M, Berger T, Deisenhammer F. Differing immunogenic potentials of interferon beta preparations in multiple sclerosis patients. Journal of Multiple Sclerosis 2006; 12(6): 731-7.Gneiss C, Tripp P, Reichartseder F, Egg R, Ehling R, Lutterotti A, Khalil M, Kuenz B, Mayringer I, Reindl M, Berger T, Deisenhammer F. Differing immunogenic potentials of interferon beta preparations in multiple sclerosis patients. Journal of Multiple Sclerosis 2006; 12(6): 731–7.Cakal B, Uygunoglu U, Saip S, Altintas A, Siva A, Badur S. BAb and MxA as functional biomarkers in routine clinical laboratories for the determination of anti-IFN-beta antibodies and their bioactivity levels in multiple sclerosis patients. Journal Immunoassay Immunochem 2014; 35(4): 398-411.Cakal B, Uygunoglu U, Saip S, Altintas A, Siva A, Badur S. BAb and MxA as functional biomarkers in routine clinical laboratories for the determination of anti-IFN-beta antibodies and their bioactivity levels in multiple sclerosis patients. Journal Immunoassay Immunochem 2014; 35(4): 398–411.Pachner AR. An improved ELISA for screening for neutralizing anti-IFN-beta antibodies in MS patients. Neurology 2003; 61(10): 1444-6.Pachner AR. An improved ELISA for screening for neutralizing anti-IFN-beta antibodies in MS patients. Neurology 2003; 61(10): 1444–6.Lapé Nixon M, Matud J, Yeh C, Prince HE. Evaluation of a multiplex bead-based screening assay for detection of binding antibodies to interferon-beta. Journal of Neuroimmunology 2009; 210(1-2): 104-7.Lapé Nixon M, Matud J, Yeh C, Prince HE. Evaluation of a multiplex bead-based screening assay for detection of binding antibodies to interferon-beta. Journal of Neuroimmunology 2009; 210(1–2): 104–7.White JT, Crossman M, Richter K, Berman M, Goyal J, Subramanyam M. Immunogenicity evaluation strategy for a second-generation therapeutic, PEG-IFN-β-1a. Bioanalysis 2015; 7(21): 2801-11.White JT, Crossman M, Richter K, Berman M, Goyal J, Subramanyam M. Immunogenicity evaluation strategy for a second-generation therapeutic, PEG-IFN-â-1a. Bioanalysis 2015; 7(21): 2801–11.Ohta M, Ohta K, Ma J, Takeuchi J, Saida T, Nishimura M, Itoh N. Clinical and Analytical Evaluation of an Enzyme Immunoassay for Myelin Basic Protein in Cerebrospinal Fluid. Clinical Chemistry 2000; 46(9): 1326-30.Ohta M, Ohta K, Ma J, Takeuchi J, Saida T, Nishimura M, Itoh N. Clinical and Analytical Evaluation of an Enzyme Immunoassay for Myelin Basic Protein in Cerebrospinal Fluid. Clinical Chemistry 2000; 46(9): 1326–30.Zoghbi J, Xu J, Grabert R, Theobald V, Richards S. A breakthrough novel method to resolve the drug and target interference problem in immunogenicity assays. Journal of Immunological Methods 2015; 426: 62-9.Zoghbi J, Xu J, Grabert R, Theobald V, Richards S. A breakthrough novel method to resolve the drug and target interference problem in immunogenicity assays. Journal of Immunological Methods 2015; 426: 62–9.Schmidt E, Hennig K, Mengede C, Zillikens D, Kromminga A. Immunogenicity of rituximab in patients with severe pemphigus. Clinical Immunology 2009; 132(3): 334-41.Schmidt E, Hennig K, Mengede C, Zillikens D, Kromminga A. Immunogenicity of rituximab in patients with severe pemphigus. Clinical Immunology 2009; 132(3): 334–41.Patton A, Mullenix MC, Swanson SJ, Koren E. An acid dissociation bridging ELISA for detection of antibodies directed against therapeutic proteins in the presence of antigen. Journal of Immunological Methods 2005; 304: 189-95.Patton A, Mullenix MC, Swanson SJ, Koren E. An acid dissociation bridging ELISA for detection of antibodies directed against therapeutic proteins in the presence of antigen. Journal of Immunological Methods 2005; 304: 189–95.Shankar G, Devanarayan V, Amaravadi L, Barrett YC, Bowsher R, Finco-Kent D, Fiscella M, Gorovits B, Kirschner S, Moxness M, Parish T, Quarmby V, Smith H, Smith W, Zuckerman LA, Koren E. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. Journal of Pharmaceutical and Biomedical Analysis 2008; 48(5): 1267-81.Shankar G, Devanarayan V, Amaravadi L, Barrett YC, Bowsher R, Finco-Kent D, Fiscella M, Gorovits B, Kirschner S, Moxness M, Parish T, Quarmby V, Smith H, Smith W, Zuckerman LA, Koren E. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. Journal of Pharmaceutical and Biomedical Analysis 2008; 48(5): 1267–81.Guidance for Industry Immunogenicity Assessment for Therapeutic Protein Products. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM338856.pdf.Guidance for Industry Immunogenicity Assessment for Therapeutic Protein Products. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM338856.pdf

The authors declare that there are no conflicts of interest present.