title: Classification of glass particles in parenteral product vials by visual, microscopic, and spectroscopic methods.
abstract: Glass vials have been used as primary containers for parenteral drugs including biopharmaceuticals. Different types of glass-related particles, although in low occurrence rate, may be adventitiously introduced in these parenterals. Proper classification and investigations of these glass-related particles may help to understand their formation, improve process control, reduce glass-related particles, and deliver safe parenteral drugs to patients. In this article, we introduced a classification scheme, and identification procedures and methods, for the glass-related particles. We propose to classify them as glass chip, glass lamella/flake, and silica gel. Eight characteristics for each glass particle type have been identified and described for the visual inspection method. The limitations of the visual method and the need to correlate visual results with forensic analysis are discussed. Using representative examples from each type of glass particle, this study summarized their forensic differentiations based on microscopic methods of optical microscopy, scanning electron microscopy, micro-flow imaging, and spectroscopic methods of dnergy-dispersive spectroscopy and Fourier transform infrared spectroscopy. The mechanisms of glass particle formation are listed as references for drug development scientists to investigate the root causes and improve process control on visible glass particles in parenteral vials.
  Glass vials have been used as primary containers for parenteral drugs including biopharmaceuticals. Different types of glass-related particles, although in low occurrence rate, may be adventitiously introduced in these parenterals. Proper classification and investigations of these glass-related particles may help to understand their formation, improve process control, reduce glass-related particles, and deliver safe parenteral drugs to patients. In this article, we introduced a classification scheme, and identification procedures and methods, for the glass-related particles. We propose to classify them as glass chip, glass lamella/flake, and silica gel. Using representative examples from each type of glass particle, this study summarized their forensic differentiations based on microscopic and spectroscopic methods. The mechanisms of glass particle formation are listed as references for drug development scientists to investigate the root causes and improve process control on visible glass particles in parenteral vials.
authors.affiliation: Department of Drug Product Development, Amgen Inc., Thousand Oaks, CA guiyangl@amgen.com.
authors.forename: Gary Guiyang
authors.initials: GG
authors.lastname: Li
authors.affiliation: Department of Drug Product Development, Amgen Inc., Thousand Oaks, CA.
authors.forename: Shawn
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Drug Product Development, Amgen Inc., Thousand Oaks, CA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Jiao
authors.affiliation: Department of Drug Product Development, Amgen Inc., Thousand Oaks, CA.
authors.forename: Zai-Qing
authors.initials: ZQ
authors.lastname: Wen
mesh_terms: D016503:Drug Delivery Systems; D004349:Drug Packaging; D005898:Glass / Q000737:chemistry*; D008420:Manufactured Materials; D008855:Microscopy, Electron, Scanning; D013499:Surface Properties