| Autor: |
Kang J; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA., Halseth T; Biointerfaces Institute, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI, USA., Vallejo D; Department of Chemistry, University of Michigan, Ann Arbor, MI, USA., Najafabadi ZI; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA., Sen KI; Protein Metrics Inc., San Carlos, CA, USA., Ford M; MS Bioworks, Ann Arbor, MI, USA., Ruotolo BT; Department of Chemistry, University of Michigan, Ann Arbor, MI, USA., Schwendeman A; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA. annaschw@umich.edu.; Biointerfaces Institute, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA. annaschw@umich.edu.; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI, USA. annaschw@umich.edu. |
| Abstrakt: |
Biosimilars are highly similar to, but not identical with, their originator products. As a result, structural differences between originators and biosimilars can be difficult to detect and characterize without the appropriate analytical tools. Therefore, we first focus on identifying initial structural differences between rituximab, bevacizumab, and trastuzumab originator and biosimilar pairs and later address how these differences change after applying thermal stress at 40 °C with orbital shaking for 4 weeks. Prior to incubation, we detected comparable secondary and tertiary structures for each pair and identified different levels of soluble aggregates, charge variants, and molecular weight variants due to differences in glycoforms and the number of C-terminal lysine groups. Over the course of incubation, we compared differences in charge variants and unfolding patterns. Taken together, our study provides a comparability exercise, providing information on the minor differences present between originator and biosimilar products and how those differences are impacted by stress. |
