The impact of the metal interface on the stability and quality of a therapeutic fusion protein
Adrian P. Defante, Steven D. Hudson, Cavan K. Kalonia, Emma Keegan, Steven Bishop, Paul Santacroce, Satish Hasige
Subvisible particle formation which occurs after the sterile filtration step of the fill/finish process is 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 sub- visible particle counts, in comparison to a ceramic pump head. Quartz-crystal microbalance was used to quantify the primary layer, a protein irreversibly adsorbed at the solid-liquid interface, and the secondary diffuse gel like layer interacting on top of the primary layer. The results showed the mass of irreversibly protein 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 on surface-induced protein aggregation at the solid-liquid interface.