title: Free fatty acid particles in protein formulations, part 1: microspectroscopic identification.
abstract: We report, for the first time, the identification of fatty acid particles in formulations containing the surfactant polysorbate 20. These fatty acid particles were observed in multiple mAb formulations during their expected shelf life under recommended storage conditions. The fatty acid particles were granular or sand-like in morphology and were several microns in size. They could be identified by distinct IR bands, with additional confirmation from energy-dispersive X-ray spectroscopy analysis. The particles were readily distinguishable from protein particles by these methods. In addition, particles containing a mixture of protein and fatty acids were also identified, suggesting that the particulation pathways for the two particle types may not be distinct. The techniques and observations described will be useful for the correct identification of proteinaceous versus nonproteinaceous particles in pharmaceutical products.
authors.affiliation: Drug Product Development, Amgen Inc., Thousand Oaks, California, 91320.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cao
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Fesinmeyer
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pierini
authors.forename: Christine C
authors.initials: CC
authors.lastname: Siska
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Litowski
authors.forename: Stephen
authors.initials: S
authors.lastname: Brych
authors.forename: Zai-Qing
authors.initials: ZQ
authors.lastname: Wen
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Kleemann
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005227:Fatty Acids / Q000737:chemistry*; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry*; D013052:Spectrometry, X-Ray Emission; D013055:Spectrophotometry, Infrared; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D005227:Fatty Acids; D011136:Polysorbates; D013501:Surface-Active Agents
keywords: FTIR; excipients; infrared spectroscopy; microparticles; microscopy; protein formulation