Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal Antibodies
<b>Background/Objectives</b>: The stress testing of biotherapeutic products is a critical component of drug development, enabling the assessment of stability, biosimilarity, and degradation pathways. Subjecting biosimilar monoclonal antibodies to controlled stress conditions yields essen...
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2025-04-01
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| author | Merve Celik Yamaci Ceren Pamukcu Yigit Erdemgil Ahmet Emin Atik Zeynep Zulfiye Yildirim Keles Ozge Can |
| author_facet | Merve Celik Yamaci Ceren Pamukcu Yigit Erdemgil Ahmet Emin Atik Zeynep Zulfiye Yildirim Keles Ozge Can |
| author_sort | Merve Celik Yamaci |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: The stress testing of biotherapeutic products is a critical component of drug development, enabling the assessment of stability, biosimilarity, and degradation pathways. Subjecting biosimilar monoclonal antibodies to controlled stress conditions yields essential insights into their structural and functional integrity, informing formulation optimization and mitigating risks before clinical trials. In this study, biosimilar products were comprehensively characterized and compared with originator products under forced degradation. The aim was to expose the products to different stress conditions such as oxidative, pH, thermal, freeze/thaw, and agitation. The products were then tested at defined time points using validated analytical methods. <b>Methods</b>: This study employed size-exclusion chromatography to detect aggregated forms. Isoelectric focusing characterized protein charge variants (e.g., acidic/basic isoforms) from post-translational modifications, while capillary electrophoresis quantified product-related impurities (aggregates and fragments). In addition, a complement assay was used to determine the efficacy and potency under specific stress conditions. <b>Results</b>: Our findings showed that biosimilar and originator products exhibited similar degradation profiles. The biosimilar monoclonal antibody was found to be analytically similar to the originator product in terms of critical parameters related to efficacy and safety under various stress conditions such as aggregation profile, biological activity, and charge variant distribution. <b>Conclusions</b>: Forced degradation studies facilitated the comprehensive and well-validated characterization of the structure and biological activity of biosimilar monoclonal antibody products. |
| format | Article |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-ff7692f863da4745897824cbb47f43df2025-08-20T02:28:25ZengMDPI AGPharmaceuticals1424-82472025-04-0118457910.3390/ph18040579Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal AntibodiesMerve Celik Yamaci0Ceren Pamukcu1Yigit Erdemgil2Ahmet Emin Atik3Zeynep Zulfiye Yildirim Keles4Ozge Can5Department of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, 34638 Istanbul, TürkiyeBiotechnology Group, Turgut Ilaclari A.S., 41400 Kocaeli, TürkiyeBiotechnology Group, Turgut Ilaclari A.S., 41400 Kocaeli, TürkiyeBiotechnology Group, Turgut Ilaclari A.S., 41400 Kocaeli, TürkiyeBiotechnology Group, Turgut Ilaclari A.S., 41400 Kocaeli, TürkiyeDepartment of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Acibadem Mehmet Ali Aydinlar University, 34638 Istanbul, Türkiye<b>Background/Objectives</b>: The stress testing of biotherapeutic products is a critical component of drug development, enabling the assessment of stability, biosimilarity, and degradation pathways. Subjecting biosimilar monoclonal antibodies to controlled stress conditions yields essential insights into their structural and functional integrity, informing formulation optimization and mitigating risks before clinical trials. In this study, biosimilar products were comprehensively characterized and compared with originator products under forced degradation. The aim was to expose the products to different stress conditions such as oxidative, pH, thermal, freeze/thaw, and agitation. The products were then tested at defined time points using validated analytical methods. <b>Methods</b>: This study employed size-exclusion chromatography to detect aggregated forms. Isoelectric focusing characterized protein charge variants (e.g., acidic/basic isoforms) from post-translational modifications, while capillary electrophoresis quantified product-related impurities (aggregates and fragments). In addition, a complement assay was used to determine the efficacy and potency under specific stress conditions. <b>Results</b>: Our findings showed that biosimilar and originator products exhibited similar degradation profiles. The biosimilar monoclonal antibody was found to be analytically similar to the originator product in terms of critical parameters related to efficacy and safety under various stress conditions such as aggregation profile, biological activity, and charge variant distribution. <b>Conclusions</b>: Forced degradation studies facilitated the comprehensive and well-validated characterization of the structure and biological activity of biosimilar monoclonal antibody products.https://www.mdpi.com/1424-8247/18/4/579monoclonal antibodybiosimilar mAbforced degradationsize exclusion chromatographyisoelectric focusingcapillary electrophoresis |
| spellingShingle | Merve Celik Yamaci Ceren Pamukcu Yigit Erdemgil Ahmet Emin Atik Zeynep Zulfiye Yildirim Keles Ozge Can Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal Antibodies Pharmaceuticals monoclonal antibody biosimilar mAb forced degradation size exclusion chromatography isoelectric focusing capillary electrophoresis |
| title | Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal Antibodies |
| title_full | Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal Antibodies |
| title_fullStr | Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal Antibodies |
| title_full_unstemmed | Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal Antibodies |
| title_short | Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal Antibodies |
| title_sort | comparative forced degradation study of anticomplement c5 biosimilar and originator monoclonal antibodies |
| topic | monoclonal antibody biosimilar mAb forced degradation size exclusion chromatography isoelectric focusing capillary electrophoresis |
| url | https://www.mdpi.com/1424-8247/18/4/579 |
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