title: Tungsten-induced protein aggregation: solution behavior.
abstract: Tungsten has been associated with protein aggregation in prefilled syringes (PFSs). This study probed the relationship between PFSs, tungsten, visible particles, and protein aggregates. Experiments were carried out spiking solutions of two different model proteins with tungsten species obtained from the extraction of tungsten pins typically used in syringe manufacturing processes. These results were compared to those obtained with various soluble tungsten species from commercial sources. Although visible protein particles and aggregates were induced by tungsten from both sources, the extract from tungsten pins was more effective at inducing the formation of the soluble protein aggregates than the tungsten from other sources. Furthermore, our studies showed that the effect of tungsten on protein aggregation is dependent on the pH of the buffer used, the tungsten species, and the tungsten concentration present. The lower pH and increased tungsten concentration induced more protein aggregation. The protein molecules in the tungsten-induced aggregates had mostly nativelike structure, and aggregation was at least partly reversible. The aggregation was dependent on tungsten and protein concentration, and the ratio of these two and appears to arise through electrostatic interaction between protein and tungsten molecules. The level of tungsten required from the various sources was different, but in all cases it was at least an order of magnitude greater than the typical soluble tungsten levels measured in commercial PFS.
authors: Formulation and Analytical Resources, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA. yjiang@amgen.com
authors: Yijia
authors: Y
authors: Jiang
authors: Yasser
authors: Y
authors: Nashed-Samuel
authors: Cynthia
authors: C
authors: Li
authors: Wei
authors: W
authors: Liu
authors: Joey
authors: J
authors: Pollastrini
authors: David
authors: D
authors: Mallard
authors: Zai-Qing
authors: ZQ
authors: Wen
authors: Kiyoshi
authors: K
authors: Fujimori
authors: Monica
authors: M
authors: Pallitto
authors: Lisa
authors: L
authors: Donahue
authors: Grace
authors: G
authors: Chu
authors: Gianni
authors: G
authors: Torraca
authors: Aylin
authors: A
authors: Vance
authors: Tony
authors: T
authors: Mire-Sluis
authors: Erwin
authors: E
authors: Freund
authors: Janice
authors: J
authors: Davis
authors: Linda
authors: L
authors: Narhi
mesh_terms: D002021:Buffers; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D008027:Light; D013058:Mass Spectrometry; D010316:Particle Size; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012542:Scattering, Radiation; D012996:Solutions; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013059:Spectrum Analysis, Raman; D014414:Tungsten / Q000737:chemistry*
chemical_list: D002021:Buffers; D011506:Proteins; D012996:Solutions; D014414:Tungsten