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