Preview

Fine Chemical Technologies

Advanced search

Development and validation of a method for the determination of the specific activity of recombinant monoclonal antibody eculizumab

https://doi.org/10.32362/2410-6593-2020-15-2-77-85

Full Text:

Abstract

Objectives. Developing reliable and accurate analytical methods is necessary for comparative pharmaceutical analysis using physicochemical, biological (in vitro), preclinical, and clinical trials. The main objective of this study was to develop and validate an in vitro method for determining the specific activity of the recombinant monoclonal antibody eculizumab.

Methods. The method of indirect enzyme immunoassay was used in the study.

Results. A method for determining the specific activity of the humanized recombinant monoclonal antibody eculizumab was described and validated for the first time. A comparative evaluation of the specific activity of Soliris® (Alexion Pharmaceuticals Inc., USA), and its biosimilar PRK-001 (Pharmapark, Russia) was performed using the developed method.

Conclusions. The similarity of PRK-001 and the original Soliris® in relation to their specific activity, that is, binding to the human complement system C5 protein, was proved. 

About the Authors

D. I. Zybin
PHARMAPARK
Russian Federation

Dmitry I. Zybin, Chief Chemist-Analyst

8, b. 1, Nauchnyi proezd, Moscow, 117246



A. S. Seregin
Scientific Center “Kurchatov Institute,” Research Institute for Genetics and Selection of Industrial Microorganisms
Russian Federation

Aleksandr S. Seregin, Postgraduate Student

1, 1st Dorozhnyi pr., Moscow, 117545



A. D. Askretkov
PHARMAPARK
Russian Federation

Aleksandr D. Askretkov, Chief Chemist-Analyst

8, b. 1, Nauchnyi proezd, Moscow, 117246



N. V. Orlova
Scientific Center “Kurchatov Institute,” Research Institute for Genetics and Selection of Industrial Microorganisms
Russian Federation

Natalya V. Orlova, Cand. of Sci., Head of Research Laboratory

1, 1st Dorozhnyi pr., Moscow, 117545



Yu. A. Seregin
Scientific Center “Kurchatov Institute,” Research Institute for Genetics and Selection of Industrial Microorganisms
Russian Federation

Yuri A. Seregin, Cand. of Sci., Deputy Director

1, 1st Dorozhnyi pr., Moscow, 117545



A. I. Prostyakova
M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Russian Federation

Anna I. Prostyakova, Cand. of Sci., Researcher, Laboratory of Polymers for Biology

16/10, Miklukho-Maklaya ul., Moscow, 117997



D. V. Kapustin
M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Russian Federation

Dmitry V. Kapustin, Cand. of Sci., Head of Polymeric Sorbent Laboratory

16/10, Miklukho-Maklaya ul., Moscow, 117997



References

1. Hill A., Platts P.J., Smith A. The incidence and prevalence of paroxysmal nocturnal hemoglobinuria (PNH) and survival of patients in Yorkshire. Blood. 2006;108(11):985. https://doi.org/10.1182/blood.V108.11.985.985

2. Pu J.J., Brodsky R.A. Paroxysmal nocturnal hemoglobinuria from bench to bedside. ClinTranslSci. 2011;4(3):219‐224. https://doi.org/10.1111/j.17528062.2011.00262.x

3. Devalet B., Mullier F., Chatelain B., Dogne J.M., Chatelain C. Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria: a review. Eur. J. Haematol. 2015;95(3):190‐198. https://doi.org/10.1111/ejh.12543

4. Höchsmann B., Rojewski M., Schrezenmeier H. Paroxysmal nocturnal hemoglobinuria (PNH): higher sensitivity and validity in diagnosis and serial monitoring by flow cytometric analysis of reticulocytes. Ann. Hematol. 2011;90(8):887-899. https://doi.org/10.1007/s00277-011-1177-4

5. Brodsky R.A., Young N.S., Antonioli E. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008;111(4):1840-1847. https://doi.org/10.1182/blood-2007-06-094136

6. Tegla C.A., Cudrici C., Patel S. Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol. Res. 2011;51(1):45–60. https://doi.org/10.1007/s12026011-8239-5

7. Ricklin D., Hajishengallis G., Yang K., Lambris J.D. Complement: a key system for immune surveillance and homeostasis. Nat. Immunol. 2010;11(9):785-797. https://doi.org/10.1038/ni.1923

8. Dubois E.A., Cohen A.F. Eculizumab. Br. J. Clin. Pharmacol. 2009;68(3):318-319. https://doi.org/10.1111/j.1365-2125.2009.03491.x

9. Khedraki R., Noor Z., Rick J. The Most Expensive Drug in the World: To Continue or Discontinue, That Is the Question. Fed. Pract. 2016;33(7):22-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366567/

10. Harder M. J., Kuhn N., Schrezenmeier H., et al. Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation. Blood. 2016;129(8):970-980. https://doi.org/10.1182/blood-2016-08-732800

11. Kelly R. J., Höchsmann B., Szer J., et al. Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria. N. Engl. J. Med. 2015;373(11):1032-1039. https://doi.org/10.1056/NEJMoa1502950

12. Wehling C., Amon O., Bommer M. Monitoring of complement activation biomarkers and eculizumab in complement-mediated renal disorders. Clin. Exp. Immunol. 2016;187(2):304-315. https://doi.org/10.1111/cei.12890

13. Validation of Analytical Procedures: Text and Methodology Q2(R1). In: International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. Geneva. 2005;6-13. https://www.gmp-compliance.org/guidemgr/files/Q2(R1).pdf

14. Tijssen P. Practice and Theory of Enzyme Immunoassays. Canada: Elsevier Science; 1985. 548 p.

15. Исакова О.П., Тарасевич Ю.Ю. Обработка и визуализация данных физических экспериментов с помощью пакета Origin. Учебно-методическое пособие. Астрахань: Издательство ОГОУ ДПО «АИПКП»; 2007. 67 c. [Isakova O.P., Tarasevich Yu.Yu. Obrabotka i vizualizatsiya dannykh fizicheskikh eksperimentov s pomoshchʼyu paketa Origin (Processing and visualization of physical experiment data using the Origin package). Educational and methodological guide. Astrakhan: DPO AIPKP Publ.; 2007; 67 p. (in Russ.).]

16. Guideline on similar biological medicinal products. Committee for Medicinal Products for Human Use; 2014. 16 p. URL: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-similar-biological-medicinal-products-rev1_en.pdf


Supplementary files

1. Specific activity of three series Soliris® and PRK-001.
Subject
Type Research Instrument
View (49KB)    
Indexing metadata
2. This is to certify that the paper titled Development and validation of a method for the determination of the specific activity of recombinant monoclonal antibody eculizumab commissioned to Enago by Dmitry I. Zybin, Aleksandr S. Seregin, Aleksandr D. Askretkov, Natalya V. Orlova, Yuri A. Seregin, Anna I. Prostyakova, Dmitry V. Kapustin has been edited by Enago, an editing brand of Crimson Interactive Inc.
Subject CERTIFICATE OF EDITING
Type Other
View (423KB)    
Indexing metadata

A method for determining the specific activity of the humanized recombinant monoclonal antibody eculizumab was designed and validated. A comparative evaluation of the specific activity of Soliris® (Alexion Pharmaceuticals Inc., USA) as well as biosimilar PRK-001 (Pharmapark, Russia) was performed using the developed method. The similarity between PRK-001 and Soliris® in relation to their specific activity, i.e., binding to the human complement system C5 protein, was confirmed.

For citation:


Zybin D.I., Seregin A.S., Askretkov A.D., Orlova N.V., Seregin Yu.A., Prostyakova A.I., Kapustin D.V. Development and validation of a method for the determination of the specific activity of recombinant monoclonal antibody eculizumab. Fine Chemical Technologies. 2020;15(2):77-85. https://doi.org/10.32362/2410-6593-2020-15-2-77-85

Views: 103


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2410-6593 (Print)
ISSN 2686-7575 (Online)