Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation
Therapeutic mAbs show a specific “charge fingerprint” that may affect safety and efficacy, and, as such, it is often identified as a critical quality attribute (CQA). Capillary iso-electric focusing (cIEF), commonly used for the evaluation of such CQA, provides an analytical tool to investigate mAb...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2313737 |
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| author | Alessandro Ascione Marcello Belfiore Jaana Vesterinen Mihaela Buda Wolf Holtkamp Francesca Luciani |
| author_facet | Alessandro Ascione Marcello Belfiore Jaana Vesterinen Mihaela Buda Wolf Holtkamp Francesca Luciani |
| author_sort | Alessandro Ascione |
| collection | DOAJ |
| description | Therapeutic mAbs show a specific “charge fingerprint” that may affect safety and efficacy, and, as such, it is often identified as a critical quality attribute (CQA). Capillary iso-electric focusing (cIEF), commonly used for the evaluation of such CQA, provides an analytical tool to investigate mAb purity and identity across the product lifecycle. Here, we discuss the results of an analysis of a panel of antibody products by conventional and whole-column imaging cIEF systems performed as part of European Pharmacopoeia activities related to development of “horizontal standards” for the quality control of monoclonal antibodies (mAbs). The study aimed at designing and verifying an independent and transversal cIEF procedure for the reliable analysis of mAbs charge variants. Despite the use of comparable experimental conditions, discrepancies in the charge profile and measured isoelectric points emerged between the two cIEF systems. These data suggest that the results are method-dependent rather than absolute, an aspect known to experts in the field and pharmaceutical industry, but not suitably documented in the literature. Critical implications from analytical and regulatory perspectives, are herein thoughtfully discussed, with a special focus on the context of market surveillance and identification of falsified medicines. |
| format | Article |
| id | doaj-art-90b4b78ca43542ea9001ea85f6de584f |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-90b4b78ca43542ea9001ea85f6de584f2025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2313737Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situationAlessandro Ascione0Marcello Belfiore1Jaana Vesterinen2Mihaela Buda3Wolf Holtkamp4Francesca Luciani5National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, ItalyNational Centre for Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, ItalyLaboratory Department, Finnish Medicines Agency, Helsinki, FinlandEuropean Pharmacopoeia Department, European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe, Strasbourg, FranceSection IMG 3 “Product Testing of Immunological Biomedicines”, Paul-Ehrlich-Institut, Langen, GermanyNational Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, ItalyTherapeutic mAbs show a specific “charge fingerprint” that may affect safety and efficacy, and, as such, it is often identified as a critical quality attribute (CQA). Capillary iso-electric focusing (cIEF), commonly used for the evaluation of such CQA, provides an analytical tool to investigate mAb purity and identity across the product lifecycle. Here, we discuss the results of an analysis of a panel of antibody products by conventional and whole-column imaging cIEF systems performed as part of European Pharmacopoeia activities related to development of “horizontal standards” for the quality control of monoclonal antibodies (mAbs). The study aimed at designing and verifying an independent and transversal cIEF procedure for the reliable analysis of mAbs charge variants. Despite the use of comparable experimental conditions, discrepancies in the charge profile and measured isoelectric points emerged between the two cIEF systems. These data suggest that the results are method-dependent rather than absolute, an aspect known to experts in the field and pharmaceutical industry, but not suitably documented in the literature. Critical implications from analytical and regulatory perspectives, are herein thoughtfully discussed, with a special focus on the context of market surveillance and identification of falsified medicines.https://www.tandfonline.com/doi/10.1080/19420862.2024.2313737Charge heterogeneity profilecIEFidentityisoelectric pointpurityquality control |
| spellingShingle | Alessandro Ascione Marcello Belfiore Jaana Vesterinen Mihaela Buda Wolf Holtkamp Francesca Luciani Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation mAbs Charge heterogeneity profile cIEF identity isoelectric point purity quality control |
| title | Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation |
| title_full | Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation |
| title_fullStr | Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation |
| title_full_unstemmed | Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation |
| title_short | Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation |
| title_sort | charge heterogeneity of therapeutic monoclonal antibodies by different cief systems views on the current situation |
| topic | Charge heterogeneity profile cIEF identity isoelectric point purity quality control |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2313737 |
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