title: Effects of syringe material and silicone oil lubrication on the stability of pharmaceutical proteins.
abstract: 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.
authors.affiliation: Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan; U-Medico Inc., Suita, Osaka, 565-0871, Japan.
authors.forename: Elena
authors.initials: E
authors.lastname: Krayukhina
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Uchiyama
authors.forename: Kiichi
authors.initials: K
authors.lastname: Fukui
mesh_terms: D060908:CTLA-4 Antigen / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008153:Lubrication / Q000592:standards*; D055550:Protein Stability; D012827:Silicone Oils / Q000737:chemistry*; D013594:Syringes / Q000592:standards*
chemical_list: D060908:CTLA-4 Antigen; D007074:Immunoglobulin G; D012827:Silicone Oils
keywords: HPLC (high-performance/pressure liquid chromatography); UV/Vis spectroscopy; analytical ultracentrifugation; biopharmaceuticals characterization; imaging methods; physical stability; prefilled syringe; protein aggregation; silicone oil; subvisible particles