Forced Degradation Testing as Complementary Tool for Biosimilarity Assessment
| Autor: | Volker Sandig, Jan Felix Joseph, Maria Kristina Parr, Yan Dyck, Karsten Winkler, Wolfgang Jabs, Daniel Rehm |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Bevacizumab
medicine.drug_class Bioengineering structure reactivity relationship QTOF-MS bevacizumab Monoclonal antibody 01 natural sciences lcsh:Technology Article 03 medical and health sciences chemistry.chemical_compound middle-up approach medicine liquid chromatography-mass spectrometry (LC-MS) lcsh:QH301-705.5 030304 developmental biology 0303 health sciences Chromatography Methionine Chemistry lcsh:T 010401 analytical chemistry Biosimilar biopharmaceuticals Infliximab 0104 chemical sciences Biopharmaceutical biosimilar forced stability testing infliximab lcsh:Biology (General) Forced degradation Critical quality attributes medicine.drug |
| Zdroj: | Bioengineering, Vol 6, Iss 3, p 62 (2019) Bioengineering, 6(3):62 Bioengineering Volume 6 Issue 3 |
| ISSN: | 2306-5354 |
| Popis: | Oxidation of monoclonal antibodies (mAbs) can impact their efficacy and may therefore represent critical quality attributes (CQA) that require evaluation. To complement classical CQA, bevacizumab and infliximab were subjected to oxidative stress by H2O2 for 24, 48, or 72 h to probe their oxidation susceptibility. For investigation, a middle-up approach was used utilizing liquid chromatography hyphenated with mass spectrometry (LC-QTOF-MS). In both mAbs, the Fc/2 subunit was completely oxidized. Additional oxidations were found in the light chain (LC) and in the Fd&rsquo subunit of infliximab, but not in bevacizumab. By direct comparison of methionine positions, the oxidized residues in infliximab were assigned to M55 in LC and M18 in Fd&rsquo The forced oxidation approach was further exploited for comparison of respective biosimilar products. Both for bevacizumab and infliximab, comparison of posttranslational modification profiles demonstrated high similarity of the unstressed reference product (RP) and the biosimilar (BS). However, for bevacizumab, comparison after forced oxidation revealed a higher susceptibility of the BS compared to the RP. It may thus be considered a useful tool for biopharmaceutical engineering, biosimilarity assessment, as well as for quality control of protein drugs. |
| Databáze: | OpenAIRE |
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