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/Unit :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
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.
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