title: Subvisible (2-100 μm) Particle Analysis During Biotherapeutic Drug Product Development: Part 1, Considerations and Strategy.
abstract: Measurement and characterization of subvisible particles (defined here as those ranging in size from 2 to 100 μm), including proteinaceous and nonproteinaceous particles, is an important part of every stage of protein therapeutic development. The tools used and the ways in which the information generated is applied depends on the particular product development stage, the amount of material, and the time available for the analysis. In order to compare results across laboratories and products, it is important to harmonize nomenclature, experimental protocols, data analysis, and interpretation. In this manuscript on perspectives on subvisible particles in protein therapeutic drug products, we focus on the tools available for detection, characterization, and quantification of these species and the strategy around their application.
authors.affiliation: Amgen, Process Development, Thousand Oaks, California. Electronic address: lnarhfooti@amgen.com.
authors.forename: Linda O
authors.initials: LO
authors.lastname: Narhi
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Vincent
authors.initials: V
authors.lastname: Corvari
authors.affiliation: NIST, Biomolecular Measurement Division, Gaithersburg, Maryland.
authors.forename: Dean C
authors.initials: DC
authors.lastname: Ripple
authors.affiliation: Bristol-Myers Squibb, Molecular and Analytical Development, New Jersey.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Afonina
authors.affiliation: Merck Serono Tiburtina Site, Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Cecchini
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Defelippis
authors.affiliation: Boehringer Ingelheim Pharma GmbH and Company KG, Biopharmaceuticals, Biberach an der Riss 88397, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Garidel
authors.affiliation: Boehringer Ingelheim Pharma GmbH and Company KG, Biopharmaceuticals, Biberach an der Riss 88397, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Herre
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharma Technical Development Europe (Biologics) Analytical Development and Quality Control, Basel, 4070, Switzerland.
authors.forename: Atanas V
authors.initials: AV
authors.lastname: Koulov
authors.affiliation: Janssen R&D LLC, Malvern, Pennsylvania.
authors.forename: Tony
authors.initials: T
authors.lastname: Lubiniecki
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharma Technical Development Europe (Biologics) Pharmaceutical Development and Supplies, Basel, 4070, Switzerland.
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.affiliation: BD Medical-Pharmaceutical Systems, CEDEX Pont de Claix 38801, France.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mangiagalli
authors.affiliation: GlaxoSmithKline, King of Prussia, Pennsylvania.
authors.forename: Douglas
authors.initials: D
authors.lastname: Nesta
authors.affiliation: Genzyme Corporation, Framingham, Massachusetts.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Perez-Ramirez
authors.affiliation: Amgen, West Greenwich, Rhode Islands.
authors.forename: Alla
authors.initials: A
authors.lastname: Polozova
authors.affiliation: Merck Serono Tiburtina Site, Rome, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Rossi
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharma Technical Development Europe (Biologics) Pharmaceutical Development and Supplies, Basel, 4070, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Biogen Idec, Cambridge, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Simler
authors.affiliation: Pfizer Inc., Chesterfield, Missouri.
authors.forename: Satish
authors.initials: S
authors.lastname: Singh
authors.affiliation: Human Genome Sciences, Inc., Rockville, Maryland.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Spitznagel
authors.affiliation: Biogen Idec, Cambridge, Massachusetts.
authors.forename: Andrew
authors.initials: A
authors.lastname: Weiskopf
authors.affiliation: Janssen R&D, Schaffhausen, Switzerland.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wuchner
mesh_terms: D000818:Animals; D004339:Drug Compounding / Q000379:methods; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D008027:Light; D008853:Microscopy / Q000379:methods; D010316:Particle Size; D066329:Protein Aggregates; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry*; D012542:Scattering, Radiation
chemical_list: D066329:Protein Aggregates; D011506:Proteins
keywords: biotechnology; light-scattering; microparticles; microscopy; particle size; physical stability; protein aggregation; protein formulation