Characterization of Subvisible Particles in Biotherapeutic Prefilled Syringes: The Role of Polysorbate and Protein on the Formation of Silicone Oil and Protein Subvisible Particles After Drop Shock
| Autor: | Marisa K. Joubert, Nathan H. Joh, Linda O. Narhi, Gregory V. Barnett, Nancy Jiao, Twinkle R. Christian, Shawn Cao |
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| Rok vydání: | 2020 |
| Předmět: |
Drug Compounding
Polysorbates Pharmaceutical Science 02 engineering and technology Buffers Protein aggregation 030226 pharmacology & pharmacy Flow imaging Protein Aggregates Surface-Active Agents 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Stability Pulmonary surfactant Silicone Oils Protein particles Particle Size Drug Packaging Polysorbate Chromatography Protein Stability Syringes Drop (liquid) Antibodies Monoclonal Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Silicone oil chemistry Immunoglobulin G Proteolysis Stress Mechanical Particle size 0210 nano-technology |
| Zdroj: | Journal of Pharmaceutical Sciences. 109:640-645 |
| ISSN: | 0022-3549 |
| Popis: | Subvisible particles (SbVPs) are a critical quality attribute for biotherapeutics. Particle content in prefilled syringes (PFSs) of a biotherapeutic can include protein particles and silicone oil particles (SiOP). Here, a real-world protein therapeutic PFS shows that although polysorbate is effective in preventing protein particle formation, it also leads to the formation of SiOP. PFSs of protein and buffer formulations in the presence and absence of polysorbate are subjected to a drop shock to generate SbVP and the effect of polysorbate and protein in generating SbVP is investigated. Particle characterization by light obscuration and flow imaging shows that polysorbate prevents protein particle formation as intended, but the presence of polysorbate substantially increases the formation of SiOP. The protein itself also acts as a surfactant and leads to increased SiOP, but to a lesser degree compared to polysorbate. In a separate companion study by Joh et al., the risk of immunogenicity was assessed using in vivo and in vitro models. Flow imaging distinguishes between SiOP and protein particles and enables risk assessment of the natures of different SbVP in PFSs. |
| Databáze: | OpenAIRE |
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