Accelerated Aggregation Studies of Monoclonal Antibodies: Considerations for Storage Stability
| Autor: | Jan Massant, Paolo Arosio, Pieter-Jan Vermeire, Ruben Wälchli |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.drug_class
Dimer Drug Compounding Drug Storage Kinetics Pharmaceutical Science 02 engineering and technology Protein aggregation Monoclonal antibody 030226 pharmacology & pharmacy Stability (probability) 03 medical and health sciences chemistry.chemical_compound Protein Aggregates 0302 clinical medicine Drug Stability medicine Particle Size Protein Stability Temperature Monoclonal immunoglobulin Antibodies Monoclonal 021001 nanoscience & nanotechnology Monomer chemistry Immunoglobulin G Biophysics Particle size 0210 nano-technology |
| Zdroj: | Journal of pharmaceutical sciences. 109(1) |
| ISSN: | 1520-6017 |
| Popis: | Aggregation of mAbs is a crucial concern with respect to their safety and efficacy. Among the various properties of protein aggregates, it is emerging that their size can potentially impact their immunogenicity. Therefore, stability studies of antibody formulations should not only evaluate the rate of monomer loss but also determine the size distribution of the protein aggregates, which in turn depends on the aggregation mechanism. Here, we study the aggregation behavior of different formulations of 2 monoclonal immunoglobulins (IgGs) in the temperature range from 5°C to 50°C over 52 weeks of storage. We show that the aggregation kinetics of both antibodies follow non-Arrhenius behavior and that the aggregation mechanisms change between 40°C and 5°C, leading to different types of aggregates. Specifically, for a given monomer conversion, dimer formation dominates at low temperatures, while larger aggregates are formed at higher temperatures. We further show that the stability ranking of different molecules as well as of different formulations is drastically different at 40°C and 5°C while it correlates better between 30°C and 5°C. Our findings have implications for the level of information provided by accelerated aggregation studies with respect to protein stability under storage conditions. |
| Databáze: | OpenAIRE |
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