Krayukhina Elena, Tsumoto Kouhei, Uchiyama Susumu, Fukui Kiichi
Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan; U-Medico Inc., Suita, Osaka, 565-0871, Japan.
J Pharm Sci. 2015 Feb;104(2):527-35. doi: 10.1002/jps.24184. Epub 2014 Sep 24.
Currently, polymer-based prefillable syringes are being promoted to the pharmaceutical market because they provide an increased break resistance relative to traditionally used glass syringes. Despite this significant advantage, the possibility that barrel material can affect the oligomeric state of the protein drug exists. The present study was designed to compare the effect of different syringe materials and silicone oil lubrication on the protein aggregation. The stability of a recombinant fusion protein, abatacept (Orencia), and a fully human recombinant immunoglobulin G1, adalimumab (Humira), was assessed in silicone oil-free (SOF) and silicone oil-lubricated 1-mL glass syringes and polymer-based syringes in accelerated stress study. Samples were subjected to agitation stress, and soluble aggregate levels were evaluated by size-exclusion chromatography and verified with analytical ultracentrifugation. In accordance with current regulatory expectations, the amounts of subvisible particles resulting from agitation stress were estimated using resonant mass measurement and dynamic flow-imaging analyses. The amount of aggregated protein and particle counts were similar between unlubricated polymer-based and glass syringes. The most significant protein loss was observed for lubricated glass syringes. These results suggest that newly developed SOF polymer-based syringes are capable of providing biopharmaceuticals with enhanced physical stability upon shipping and handling.
目前，基于聚合物的预填充注射器正在向医药市场推广，因为相对于传统使用的玻璃注射器，它们具有更高的抗破损性。尽管有这一显著优势，但注射器筒材料可能会影响蛋白质药物的寡聚状态。本研究旨在比较不同注射器材料和硅油润滑对蛋白质聚集的影响。在加速应力研究中，评估了重组融合蛋白阿巴西普（Orencia）和全人重组免疫球蛋白G1阿达木单抗（Humira）在无硅油（SOF）和硅油润滑的1 mL玻璃注射器以及基于聚合物的注射器中的稳定性。对样品施加搅拌应力，并通过尺寸排阻色谱法评估可溶性聚集体水平，并用分析超速离心法进行验证。根据当前的监管预期，使用共振质量测量和动态流动成像分析来估计搅拌应力产生的亚可见颗粒数量。未润滑的基于聚合物的注射器和玻璃注射器之间的聚集蛋白量和颗粒计数相似。润滑的玻璃注射器中观察到最显著的蛋白质损失。这些结果表明，新开发的无硅油聚合物基注射器能够在运输和处理过程中为生物制药提供更高的物理稳定性。
