Analysis of Aggregates and Particles in Protein Pharmaceuticals

Contributors ix Preface xiii Glossary xv 1 The Critical Need for Robust Assays for Quantitation andCharacterization of Aggregates of Therapeutic Proteins 1 John F. Carpenter, Barry Cherney, and Amy S. Rosenberg I METHODS USED FOR DETECTING, QUANTIFYING, ANDSIZING OF PROTEIN AGGREGATES AND PARTICLES 9 2 Separation-Based Analytical Methods for Measuring ProteinAggregation 11 Jun Liu, Barthelemy Demeule, and Steven J. Shire 3 Laser Light Scattering-Based Techniques Used for theCharacterization of Protein Therapeutics 37 John den Engelsman, Fabian Kebbel, and Patrick Garidel 4 Online Detection Methods and Emerging Techniques for SolubleAggregates in Protein Pharmaceuticals 61 Tapan K. Das 5 Analytical Methods to Measure Subvisible Particulates 85 Shawn Cao, Linda Narhi, Yijia Jiang, and Rahul S. Rajan 6 Detection of Visible Particles in Parenteral Products117 Ronald Smulders, Hans Vos, and Hanns-Christian Mahler 7 Characterization of Aggregates and Particles Using EmergingTechniques 133 Hui Zhao, Manuel Diez, Atanas Koulov, Mariola Bozova, MarkusBluemel, and Kurt Forrer II METHODS USED TO CHARACTERIZE PROTEIN AGGREGATES ANDPARTICLES 169 8 Ultraviolet Absorption Spectroscopy 171 Reza Esfandiary and Charles Russell Middaugh 9 Fluorescence Spectroscopy to Characterize Protein Aggregatesand Particles 201 Robert A. Poole, Andrea Hawe, Wim Jiskoot, and KevinBraeckmans 10 Infrared Spectroscopy to Characterize Protein Aggregates227 Marco van de Weert and Lene Jørgensen 11 Raman Microscopy for Characterization of Particles 249 Stefan Fischer, Oliver Valet, and Markus Lankers 12 Microscopic Methods for Particle Characterization in ProteinPharmaceuticals 269 Patrick Garidel, Andrea Herre, and Werner Kliche III INTEGRATED APPROACHES TO PROTEIN AGGREGATION ANDPARTICLES 303 13 Comparison of Methods for Soluble Aggregate Detection andSize Characterization 305 John S. Philo 14 Protein Purification and Its Relation to Protein Aggregationand Particles 335 Roberto Falkenstein, Stefan Hepbildikler, Wolfgang Kuhne,Thorsten Lemm, Hans Rogl, Eva Rosenberg, Gerhard Winter, FrankZettl, and Ralf Zippelius 15 Formulation Development and Its Relation to ProteinAggregation and Particles 369 Miriam Printz and Wolfgang Friess Index 389