title: Semi-Quantitative Analysis of Inherent Visible Particles for Biopharmaceutical Products.
abstract: Visible particles must be monitored as part of the control strategy for pharmaceutical products. Extraneous (foreign) particles are not acceptable in parenteral drug products. In biopharmaceuticals, formation of protein particles is recognized as an inherent quality attribute. All protein therapeutics contain particles that vary greatly in visibility and size from invisible (sub-micron) to visible (millimeter) and, as part of the control strategy, biopharmaceutical companies are required to monitor and minimize the presence of visible and sub-visible particles in their products. There is an industry-wide unmet need for particle standards for visual inspection of protein therapeutics. A new, semi-quantitative method using particle standards for assessing the levels of small, inherent visible particles is presented. This method can be used during product development to identify a formulation that minimizes particle formation and also during release and stability testing to monitor and control inherent proteinaceous visible particles.
  Visible particles must be monitored as part of the control strategy for parenteral biopharmaceutical drug products. In these products, formation of protein particles is a natural occurrence. All protein drugs contain particles that vary greatly in visibility and size from invisible (sub-micron) to visible (millimeter), and pharmaceutical companies are required to monitor and minimize the presence of visible and sub-visible particles in their products. There is an industry-wide unmet need for particle standards for visual inspection of protein drugs. A new, semi-quantitative method using particle standards for assessing the levels of small, naturally occurring visible particles is presented. This method can be used during drug development to identify a formulation that minimizes particle formation and also during testing of final clinical or commercial drug product to monitor and control naturally occurring proteinaceous visible particles.
authors.affiliation: Analytical Biotechnology, MedImmune, Gaithersburg, MD; cashp@medimmune.com.
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Cash
authors.affiliation: Formulation Sciences, MedImmune, Gaithersburg, MD; and.
authors.forename: Roja
authors.initials: R
authors.lastname: Narwal
authors.affiliation: Analytical Biotechnology, MedImmune, Gaithersburg, MD;
authors.forename: Sophia V
authors.initials: SV
authors.lastname: Levitskaya
authors.affiliation: Analytical Biotechnology, MedImmune, Gaithersburg, MD;
authors.forename: Stephan
authors.initials: S
authors.lastname: Krause
authors.affiliation: Quality Assurance, MedImmune, Granta Park Cambridge, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Murphy
authors.affiliation: Analytical Biotechnology, MedImmune, Gaithersburg, MD;
authors.forename: Maryam
authors.initials: M
authors.lastname: Mazaheri
mesh_terms: D001688:Biological Products / Q000032:analysis* / Q000592:standards; D004340:Drug Contamination / Q000517:prevention & control; D006801:Humans; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D014796:Visual Perception
chemical_list: D001688:Biological Products; D004364:Pharmaceutical Preparations
keywords: Barium sulfate; Biotechnology; Inherent visible particles; Particle standard; Protein aggregation; Protein formulation; Proteinaceous; Proteins; Stability; Visible particles