Subvisible particle formation, which occurs after the sterile filtration step of the fill/finish process, is a challenge that may occur during the development of biotherapeutics with complex molecular structures. Here, we show that a stainless steel pump head from a rotary piston pump produces more protein aggregates, past the limit of the acceptable quality range for subvisible particle counts, in comparison to a ceramic pump head. The quartz crystal microbalance was used to quantify the primary layer, proteins irreversibly adsorbed at the solid-liquid interface, and the secondary diffuse gel-like layer interacting on top of the primary layer. The results showed that the mass of protein irreversibly adsorbed onto stainless steel sensors is greater than on an aluminum oxide surface (ceramic pump mimic). This suggests that the amount of adsorbed protein plays a role in surface-induced protein aggregation at the solid-liquid interface.

中文翻译：

---

金属界面对治疗性融合蛋白的稳定性和质量的影响。

在填充/完成过程的无菌过滤步骤之后发生的亚可见颗粒形成，是具有复杂分子结构的生物治疗药物开发过程中可能发生的挑战。在这里，我们表明，与陶瓷泵头相比，旋转活塞泵的不锈钢泵头产生了更多的蛋白质聚集体，超出了亚可见颗粒数可接受质量范围的限制。石英晶体微量天平用于定量第一层，不可逆地吸附在固液界面的蛋白质以及第二层弥散性凝胶状层在第一层的顶部相互作用。结果表明，不可逆地吸附在不锈钢传感器上的蛋白质质量大于氧化铝表面（陶瓷泵模拟物）上的蛋白质质量。