title: Factors Governing the Precision of Subvisible Particle Measurement Methods - A Case Study with a Low-Concentration Therapeutic Protein Product in a Prefilled Syringe.
abstract: OBJECTIVE
  The current study was performed to assess the precision of the principal subvisible particle measurement methods available today. Special attention was given to identifying the sources of error and the factors governing analytical performance.
  
  
  METHODS
  The performance of individual techniques was evaluated using a commercial biologic drug product in a prefilled syringe container. In control experiments, latex spheres were used as standards and instrument calibration suspensions.
  
  
  RESULTS
  The results reported in this manuscript clearly demonstrated that the particle measurement techniques operating in the submicrometer range have much lower precision than the micrometer size-range methods. It was established that the main factor governing the relatively poor precision of submicrometer methods in general and inherently, is their low sampling volume and the corresponding large extrapolation factors for calculating final results.
  
  
  CONCLUSIONS
  The variety of new methods for submicrometer particle analysis may in the future support product characterization; however, the performance of the existing methods does not yet allow for their use in routine practice and quality control.
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland.|Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland.|Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, 4056, Basel, Switzerland.
authors.forename: Anacelia
authors.initials: A
authors.lastname: Ríos Quiroz
authors.affiliation: Pharma Development, Biometry, NonClinical Biostatistics, F. Hoffmann - La Roche Ltd, Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
authors.forename: Jens
authors.initials: J
authors.lastname: Lamerz
authors.affiliation: Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Da Cunha
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
authors.forename: Adeline
authors.initials: A
authors.lastname: Boillon
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Adler
authors.affiliation: Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
authors.forename: Christof
authors.initials: C
authors.lastname: Finkler
authors.affiliation: Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, 4056, Basel, Switzerland.
authors.forename: Joerg
authors.initials: J
authors.lastname: Huwyler
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.affiliation: Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland. atanas.koulov@roche.com.
authors.forename: Atanas V
authors.initials: AV
authors.lastname: Koulov
mesh_terms: D002623:Chemistry Techniques, Analytical / Q000379:methods*; D010316:Particle Size; D066329:Protein Aggregates; D011506:Proteins / Q000737:chemistry*; D013594:Syringes
chemical_list: D066329:Protein Aggregates; D011506:Proteins
keywords: particle counting methods; precision; protein particles; subvisible particles