Anacelia Ríos Quiroz1,2,3, Jens Lamerz4, Thierry Da Cunha2, Adeline Boillon1, Michael Adler1, Christof Finkler2, Joerg Huwyler3, Roland Schmidt1, Hanns-Christian Mahler1, Atanas V Koulov5. 1. Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland. 2. Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland. 3. Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, 4056, Basel, Switzerland. 4. Pharma Development, Biometry, NonClinical Biostatistics, F. Hoffmann - La Roche Ltd, Grenzacherstrasse 124, CH-4070, Basel, Switzerland. 5. Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffman-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland. atanas.koulov@roche.com.
Abstract
PURPOSE: 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.
PURPOSE: 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.
Keywords:
particle counting methods; precision; protein particles; subvisible particles
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