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Sub-visible (2 µm to 100 µm) particle analysis during biotherapeutic drug product development: Part 1, considerations and strategy



Dean C. Ripple, Linda Narhi, Natliya Afonina, Satish Singh, Andrea Herre, Patrick Garidel, Atanas Koulov, Vincent Corvari, Thomas Spitznagel, Paolo Mangiagalli, Irene Cecchini, Klaus Wuchner, Tony Lubiniecki, Hanns-Christian Mahler, Roland Schmidt, Alla Polozova, Patricia Cash, Andrew Weiskopf, Douglas Nesta, Mara Rossi, Robert Simler


Measurement and characterization of particles in the 1 µm to 100 µm range (sub-visible particles), including protein aggregates, 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 labs and products it is important to harmonize nomenclature, experimental protocols, data analysis, and interpretation. Our task is presented in two companion papers. (i) In this first of 2 companion manuscripts on strategies for detection and quantification of micron particles in protein therapeutics the theoretical limits of these measurements, the parameters derived from the measurement related to the formation of particles, a brief description of the techniques available, the difficulty in obtaining matched blanks and standards, and the importance of sample handling, are presented. In this paper, we present several case studies that focus on the methodology or instrumentation used. (ii) Case studies in the companion paper illustrate the implementation of the proposed strategy for a variety of drug candidates or products at several stages of development.
Journal of Pharmaceutical Sciences


biotherapeutic, drug, particle, protein


Ripple, D. , Narhi, L. , Afonina, N. , Singh, S. , Herre, A. , Garidel, P. , Koulov, A. , Corvari, V. , Spitznagel, T. , Mangiagalli, P. , Cecchini, I. , Wuchner, K. , Lubiniecki, T. , Mahler, H. , Schmidt, R. , Polozova, A. , Cash, P. , Weiskopf, A. , Nesta, D. , Rossi, M. and Simler, R. (2015), Sub-visible (2 µm to 100 µm) particle analysis during biotherapeutic drug product development: Part 1, considerations and strategy, Journal of Pharmaceutical Sciences, [online], (Accessed June 24, 2024)


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Created April 1, 2015, Updated November 10, 2018