Forced Degradation of Monoclonal Antibodies After Compounding: Impact on Routine Hospital Quality Control
| Autor: | Patrice Prognon, Eric Caudron, Thomas Daniel, Emmanuel Jaccoulet |
|---|---|
| Přispěvatelé: | Chimie Analytique Pharmaceutique - Faculté de Pharmacie (Lip(Sys)2), Université Paris-Sud - Paris 11 (UP11) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Quality Control
Chromatography medicine.drug_class Chemistry Drug Compounding [SDV]Life Sciences [q-bio] Hospital quality Antibodies Monoclonal Pharmaceutical Science 02 engineering and technology 021001 nanoscience & nanotechnology Monoclonal antibody 030226 pharmacology & pharmacy Hospitals Bevacizumab 03 medical and health sciences Nivolumab 0302 clinical medicine Compounding Freezing Forced degradation medicine Stress conditions 0210 nano-technology |
| Zdroj: | Journal of Pharmaceutical Sciences-Elsevier Journal of Pharmaceutical Sciences-Elsevier, Elsevier, 2019, 108, pp.3252-3261. ⟨10.1016/j.xphs.2019.06.004⟩ |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2019.06.004⟩ |
| Popis: | Compounded therapeutic mAbs used in a hospital require quality control (QC). In our hospital, analytical QC process intended to mAbs identification and quantification is based on flow injection analysis associated with second-derivative UV spectroscopy and matching method algorithm. We studied the influence of degraded mAbs after compounding on this validated QC. Three forced stress conditions including mechanical, thermal, and freeze-thawing stresses were studied to yield degraded mAbs from 2 model compounds, that is, bevacizumab (IgG1) and nivolumab (IgG4). Different degraded mAbs were generated and were analyzed in terms of turbidity, the percentage of aggregation, size distribution, and changes in tertiary structure. Stresses showed to be mAb-dependent in terms of aggregation. Tertiary structural changes were observed in most of the stressed samples by principal component analysis of the UV second-derivative data. The structural and physicochemical modifications conducted to mismatch depending on the nature of the stress. The mismatch ranged from 17% to 72% for the mAbs, except for freeze-thawed bevacizumab for which a perfect match (100%) was reached. The quantification with an unfulfilled relative error of the concentration (i.e., > ±15%) was detected only for mechanically stressed mAbs. In conclusion, the study revealed that the influence of the mAbs and the type of stress impact on the QC of compounded mAbs. |
| Databáze: | OpenAIRE |
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