Identification of monoclonal antibody variants involved in aggregate formation – Part 2: Hydrophobicity variants
Autor: | Lukas Berger, Robina M. Meyer, Sebastian Nehring, Joerg Nerkamp, Wolfgang Friess, Stefan Scheler |
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Rok vydání: | 2021 |
Předmět: |
Biological Products
medicine.drug_class Chemistry Drug Storage Antibodies Monoclonal Pharmaceutical Science 02 engineering and technology General Medicine Computational biology Protein aggregation 021001 nanoscience & nanotechnology Monoclonal antibody 030226 pharmacology & pharmacy Protein Aggregates 03 medical and health sciences 0302 clinical medicine Protein stability Drug Stability medicine 0210 nano-technology Hydrophobic and Hydrophilic Interactions Biotechnology |
Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 160:134-142 |
ISSN: | 0939-6411 |
DOI: | 10.1016/j.ejpb.2021.01.006 |
Popis: | Monoclonal antibodies (mAbs) are valuable tools both in therapy and in diagnostic. Their tendency to aggregate is a serious concern. Since a mAb drug substance (DS) is composed of different variants, it is important for manufacturers to know the behavior and stability not only of the mAb as a whole, but also of the variants contained in the product. We present a method to separate hydrophobicity variants of a mAb and subsequently analyzed these variants for stability and aggregation propensity. We identified a potentially aggregation prone hydrophilic variant which is interrelated with another previously identified aggregation prone acidic charge variant. Additionally, we assessed the risk posed by the aggregation prone variant to the DS by spiking hydrophobicity variants into DS and did not observe an enhanced aggregation propensity. Thus we present an approach to separate, characterize and analyze the criticality of aggregation prone variants in protein DS which is a step forward to further assure drug safety. |
Databáze: | OpenAIRE |
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