Comparison of Three Complementary Analytical Techniques for the Evaluation of the Biosimilar Comparability of a Monoclonal Antibody and an Fc-Fusion Protein.
Demelenne, Alice; Ben Yahia, Arij; Lempereur, Delphineet al.
adalimumab; capillary gel electrophoresis; etanercept; reversed-phase liquid chromatography; size-exclusion chromatography; Chemistry (all); General Chemistry
Abstract :
[en] In this work, a monoclonal antibody, adalimumab, and an Fc-fusion protein, etanercept, were studied and compared to one of their biosimilars. Samples submitted to stress conditions (agitation and high temperature) were used for method development. The developed methods were also applied to samples reduced by beta-mercaptoethanol to evaluate their capability to distinguish the expected species. Capillary gel electrophoresis (CGE), reversed-phase liquid chromatography (RPLC), and size-exclusion chromatography (SEC) methods coupled with UV detection were used to analyze the biopharmaceuticals. Their complementarity was investigated. For further molecular weight determination, SEC-multi angle light scattering and RPLC-quadrupole time-of-flight were occasionally used. For adalimumab, a larger amount of fragments and aggregates was observed in the biosimilar compared with the reference product. For etanercept, more related species were found in the reference product. Those three separation techniques showed good complementarity. Indeed, RPLC enabled the separation of hydrophilic and hydrophobic degradation products. CGE provided good selectivity for several adalimumab fragments, and SEC was useful for the analysis of aggregates and certain fragments that cannot be separated by the other approaches. Moreover, those formulations were submitted to mild stress conditions (30°C, 300 rpm for 4 h) that mimic shipping conditions. No additional peak was found under these conditions for the two studied biopharmaceuticals.
Research center :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège [BE]
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Demelenne, Alice ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Ben Yahia, Arij ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Laboratory of Chemical, Pharmaceutical and Pharmacological Development of Drugs, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia
Lempereur, Delphine; Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), Quartier Hôpital, University of Liege, Liege, Belgium
Crommen, Jacques ; Université de Liège - ULiège > Département de pharmacie
Servais, Anne-Catherine ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Fradi, Ines; Laboratory of Chemical, Pharmaceutical and Pharmacological Development of Drugs, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia
Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Language :
English
Title :
Comparison of Three Complementary Analytical Techniques for the Evaluation of the Biosimilar Comparability of a Monoclonal Antibody and an Fc-Fusion Protein.
The authors acknowledge the research grants from the Walloon Region of Belgium and EU Commission (project FEDER-PHARE) for the funding of the DTIMS-QTOF instrument.
Antibody society (2021). An International Non-Profit Supporting Antibody-Related Research and Development. Antibody Therapeutics Approved or in Regulatory Review in the EU or US. Available at: https://www.antibodysociety.org/resources/approved-antibodies/(Accessed June 27, 2021).
Bang L. M. Keating G. M. (2004). Adalimumab. BioDrugs. 18, 121–139. 10.2165/00063030-200418020-00005
Berkowitz S. A. Engen J. R. Mazzeo J. R. Jones G. B. (2012). Analytical Tools for Characterizing Biopharmaceuticals and the Implications for Biosimilars. Nat. Rev. Drug Discov. 11, 527–540. 10.1038/nrd3746
Bobály B. D'Atri V. Lauber M. Beck A. Guillarme D. Fekete S. (2018). Characterizing Various Monoclonal Antibodies With Milder Reversed Phase Chromatography Conditions. J. Chromatogr. B. 1096, 1–10. 10.1016/j.jchromb.2018.07.039
Davies H. D. (2016). Infectious Complications With the Use of Biologic Response Modifiers in Infants and Children. Pediatrics. 138, e20161209. 10.1542/peds.2016-1209
Davis J. D. Deng R. Boswell C. A. Zhang Y. Li J. Fielder P. et al. (2013). Monoclonal Antibodies: From Structure to Therapeutic Application. Editors Crommelin D. J. A. Sindelar R. Meibohm B. (springer: Pharm. Biotechnol), 1–544.
Demelenne A. Napp A. Bouillenne F. Crommen J. Servais A.-C. Fillet M. (2019). Insulin Aggregation Assessment by Capillary Gel Electrophoresis without Sodium Dodecyl Sulfate: Comparison With Size-Exclusion Chromatography. Talanta. 199, 457–463. 10.1016/j.talanta.2019.02.074
Duivelshof B. L. Murisier A. Camperi J. Fekete S. Beck A. Guillarme D. et al. (2021). Therapeutic Fc‐Fusion Proteins: Current Analytical Strategies. J. Sep. Sci. 44, 35–62. 10.1002/jssc.202000765
EMEA (2003). Humira - Scientific Discussion.
European Medicines Agency, Medicines (2021). Available at: https://www.ema.europa.eu/en/medicines/field_ema_web_categories%253Aname_field/Human/ema_group_types/ema_medicine/field_ema_med_status/authorised-36/ema_medicine_types/field_ema_med_biosimilar/search_api_aggregation_ema_medicine_types/field_ema_med_biosim (Accessed June 26, 2021).
European Medicines Agency (2014). Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Quality Issues. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/01/WC500180219.pdf.
FDA (2021). Available at: https://www.fda.gov/(Accessed April 22, 2021).
Fekete S. Beck A. Veuthey J.-L. Guillarme D. (2015). Ion-Exchange Chromatography for the Characterization of Biopharmaceuticals. J. Pharm. Biomed. Anal. 113, 43–55. 10.1016/j.jpba.2015.02.037
Food and Drug administration (2021). Biosimilar Drug Information. Available at: https://www.fda.gov/drugs/biosimilars/biosimilar-product-information (Accessed June 26, 2021).
François Y. Guillarme D. (2020). “Facing the Complexity of Biopharmaceuticals Characterization,” in 36th Int. Symp. Microscale Sep. Bioanal, 36.
Füssl F. Trappe A. Cook K. Scheffler K. Fitzgerald O. Bones J. (2019). Comprehensive Characterisation of the Heterogeneity of Adalimumab via Charge Variant Analysis Hyphenated On-Line to Native High Resolution Orbitrap Mass Spectrometry. MAbs 11, 116–128. 10.1080/19420862.2018.1531664
Gherghescu I. Delgado-Charro M. B. (2021). The Biosimilar Landscape: An Overview of Regulatory Approvals by the EMA and FDA. Pharmaceutics. 13, 1–16. 10.3390/pharmaceutics13010048
Gokarn Y. Agarwal S. Arthur K. Bepperling A. Day E. S. Filoti D. et al. (2015). “Biophysical Techniques for Characterizing the Higher Order Structure and Interactions of Monoclonal Antibodies,” in State-of-the-Art Emerg. Technol. Ther. Monoclon. Antib. Charact. (ACS Symposium Series), 285–327. 10.1021/bk-2015-1201.ch006
Goldenberg M. M. (1999). Etanercept, a Novel Drug for the Treatment of Patients With Severe, Active Rheumatoid Arthritis. Clin. Ther. 21, 75–87. 10.1016/s0149-2918(00)88269-7
ICH (1996). Q2B: Validation of Analytical Procedures: Methodology, n.D. Available at: www.ich.org.
ICH (2021). ICH Official Web Site. ICH. Available at: https://www.ich.org/(Accessed January 24, 2021).
Kerr R. A. Keire D. A. Ye H. (2019). The Impact of Standard Accelerated Stability Conditions on Antibody Higher Order Structure as Assessed by Mass Spectrometry. MAbs. 11, 930–941. 10.1080/19420862.2019.1599632
Le Basle Y. Chennell P. Tokhadze N. Astier A. Sautou V. (2020). Physicochemical Stability of Monoclonal Antibodies: A Review. J. Pharm. Sci. 109, 169–190. 10.1016/j.xphs.2019.08.009
Lee N. Lee J. J. Yang H. Baek S. Kim S. Kim S. et al. (2019). Evaluation of Similar Quality Attribute Characteristics in SB5 and Reference Product of Adalimumab. MAbs. 11, 129–144. 10.1080/19420862.2018.1530920
Liddell E. (2013) Antibodies. in Immunoass. Handb (Elsevier), 245–265. 10.1016/b978-0-08-097037-0.00017-8
Liu Y. Parameswara R. Ratnayake C. Koh E. (2008). Methods and Compositions for Capillary Electrophoresis. Beckman Coulter Inc.
Miranda-hernández M. P. Valle-gonzález E. R. Ferreira-gómez D. (2015). Theoretical Approximations and Experimental Extinction Coefficients of Biopharmaceuticals. Anal. Bioanal. Chem. 408 (5), 1523–1530. 10.1007/s00216-015-9261-6
Mitoma H. Horiuchi T. Tsukamoto H. Ueda N. (2018). Molecular Mechanisms of Action of Anti-TNF-α Agents - Comparison Among Therapeutic TNF-α Antagonists. Cytokine. 101, 56–63. 10.1016/j.cyto.2016.08.014
Müller T. Winter D. (2017). Systematic Evaluation of Protein Reduction and Alkylation Reveals Massive Unspecific Side Effects by Iodine-Containing Reagents. Mol. Cell Proteomics. 16, 1173–1187. 10.1074/mcp.m116.064048
Nowak C. K. Cheung J. M. Dellatore S. Katiyar A. Bhat R. Sun J. et al. (2017). Forced Degradation of Recombinant Monoclonal Antibodies: A Practical Guide. MAbs. 9, 1217–1230. 10.1080/19420862.2017.1368602
Oshinbolu S. Wilson L. J. Lewis W. Shah R. Bracewell D. G. (2018). Measurement of Impurities to Support Process Development and Manufacture of Biopharmaceuticals. Trac Trends Anal. Chem. 101, 120–128. 10.1016/j.trac.2017.10.026
Pedersen-Bjergaard S. Gammelgaard B. Gronhaug Halvorsen T. (2019). Introduction to Pharmaceutical Analytical Chemistry. John Wiley & Sons Ltd.
Salas-Solano O. Tomlinson B. Du S. Parker M. Strahan A. Ma S. (2006). Optimization and Validation of a Quantitative Capillary Electrophoresis Sodium Dodecyl Sulfate Method for Quality Control and Stability Monitoring of Monoclonal Antibodies. Anal. Chem. 78, 6583–6594. 10.1021/ac060828p
Schmid M. Prinz T. K. Stäbler A. Sängerlaub S. (2017). Effect of Sodium Sulfite, Sodium Dodecyl Sulfate, and Urea on the Molecular Interactions and Properties of Whey Protein Isolate-Based Films. Front. Chem. 4, 49–15. 10.3389/fchem.2016.00049
Some D. Amartely H. Tsadok A. Lebendiker M. (2019). Characterization of Proteins by Size-Exclusion Chromatography Coupled to Multi-Angle Light Scattering (SEC-MALS). J. Vis. Exp. 148, 1–9. 10.3791/59615
Tamizi E. Jouyban A. (2016). Forced Degradation Studies of Biopharmaceuticals: Selection of Stress Conditions. Eur. J. Pharmaceutics Biopharmaceutics. 98, 26–46. 10.1016/j.ejpb.2015.10.016
Tebbey P. W. Varga A. Naill M. Clewell J. Venema J. (2015). Consistency of Quality Attributes for the Glycosylated Monoclonal Antibody Humira (Adalimumab). MAbs. 7, 805–811. 10.1080/19420862.2015.1073429
Venkataraman S. Manasa M. (2018). Forced Degradation Studies: Regulatory Guidance, Characterization of Drugs, and Their Degradation Products - A Review. Drug Invent. Today. 10, 137–146.
Wang G. De Jong R. N. Van Den Bremer E. T. J. Parren P. W. H. I. Heck A. J. R. (2017). Enhancing Accuracy in Molecular Weight Determination of Highly Heterogeneously Glycosylated Proteins by Native Tandem Mass Spectrometry. Anal. Chem. 89, 4793–4797. 10.1021/acs.analchem.6b05129
Waters (2020). BioResolve SEC mAb Guard and Columns.
Wen J. Arakawa T. Philo J. S. (1996). Size-Exclusion Chromatography With On-Line Light-Scattering, Absorbance, and Refractive Index Detectors for Studying Proteins and Their Interactions. Anal. Biochem. 240, 155–166. 10.1006/abio.1996.0345
Zhang J. Burman S. Gunturi S. Foley J. P. (2010). Method Development and Validation of Capillary Sodium Dodecyl Sulfate Gel Electrophoresis for the Characterization of a Monoclonal Antibody. J. Pharm. Biomed. Anal. 53, 1236–1243. 10.1016/j.jpba.2010.07.029
Zhu L. Guo Q. Guo H. Liu T. Zheng Y. Gu P. et al. (2014). Versatile Characterization of Glycosylation Modification in CTLA4-Ig Fusion Proteins by Liquid Chromatography-Mass Spectrometry. MAbs. 6, 1474–1485. 10.4161/mabs.36313
