title: Evaluation of Incremental Siliconization Levels on Soluble Aggregates, Submicron and Subvisible Particles in a Prefilled Syringe Product.
abstract: The evaluation of stability with respect to particles in prefilled syringes is complicated by the presence of silicone oil. The mobility, colloidal characteristics, and kinetic instability of silicone oil in contact with a protein formulation may be influenced in unpredictable ways by pharmaceutical variables, storage, and handling conditions. To provide insight into the impact of these variables on silicone oil originating specifically from the siliconized prefillable syringe (PFS), a series of studies were conducted at incremental syringe barrel siliconization levels. Size-exclusion chromatography and particle counting methods were used to quantitate soluble aggregates and submicron and subvisible particles in peginterferon beta-1a in a PFS siliconized with a fixed nozzle spray-on siliconization process. The effect of silicone oil on the peginterferon beta-1a molecule was examined under pharmaceutically relevant conditions, accelerated degradation, and under denaturing conditions. Resonant mass measurement was used to discriminate silicone oil from protein particles establishing that silicone oil does not mask adverse trends in non-silicone oil particles. The peginterferon beta-1a molecule was shown to be stable in the presence of silicone oil and robust with respect to the formation of soluble aggregates and submicron and subvisible particles in its PFS siliconized over the range of 0-1.2 mg silicone oil per syringe barrel.
authors: Protein Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142.
authors: Shujun
authors: S
authors: Bai
authors: Protein Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142.
authors: Pavel
authors: P
authors: Landsman
authors: Protein Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142.
authors: Andrea
authors: A
authors: Spencer
authors: Protein Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142.
authors: Daniel
authors: D
authors: DeCollibus
authors: Protein Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142.
authors: Fabian
authors: F
authors: Vega
authors: Protein Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142.
authors: Deniz B
authors: DB
authors: Temel
authors: Protein Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142.
authors: Damian
authors: D
authors: Houde
authors: Protein Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142.
authors: Olivia
authors: O
authors: Henderson
authors: Protein Pharmaceutical Development, Biogen, Cambridge, Massachusetts 02142. Electronic address: mark.brader@biogen.com.
authors: Mark L
authors: ML
authors: Brader
mesh_terms: D002850:Chromatography, Gel; D004355:Drug Stability; D016899:Interferon-beta / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D066329:Protein Aggregates; D012827:Silicone Oils / Q000737:chemistry*; D012995:Solubility; D013594:Syringes / Q000592:standards*
chemical_list: D066329:Protein Aggregates; D012827:Silicone Oils; D011092:Polyethylene Glycols; D016899:Interferon-beta; C428112:peginterferon beta-1a
keywords: biopharmaceuticals characterization biotechnology; light scattering (dynamic); particle size; pegylation; protein aggregation; protein formulation; proteins; quality by design (QBD)