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WIM JISKOOT is Professor and Head of the Biologics Formulation Group in the Leiden/Amsterdam Center for Drug Research (LACDR) at Leiden University.

Preface xiii

Glossary xv

1 The Critical Need for Robust Assays for Quantitation and Characterization of Aggregates of Therapeutic Proteins 1
John F. Carpenter, Barry Cherney, and Amy S. Rosenberg

I METHODS USED FOR DETECTING, QUANTIFYING, AND SIZING OF PROTEIN AGGREGATES ANDPARTICLES 9

2 Separation-Based Analytical Methods for Measuring Protein Aggregation 11
Jun Liu, Barthelemy Demeule, and Steven J. Shire

3 Laser Light Scattering-Based Techniques Used for the Characterization of Protein Therapeutics 37
John den Engelsman, Fabian Kebbel, and Patrick Garidel

4 Online Detection Methods and Emerging Techniques for Soluble Aggregates 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 Products 117
Ronald Smulders, Hans Vos, and Hanns-Christian Mahler

7 Characterization of Aggregates and Particles Using Emerging Techniques 133
Hui Zhao, Manuel Diez, Atanas Koulov, Mariola Bozova, Markus Bluemel, and Kurt Forrer

II METHODS USED TO CHARACTERIZE PROTEIN AGGREGATES AND PARTICLES 169

8 Ultraviolet Absorption Spectroscopy 171
Reza Esfandiary and Charles Russell Middaugh

9 Fluorescence Spectroscopy to Characterize Protein Aggregates and Particles 201
Robert A. Poole, Andrea Hawe, Wim Jiskoot, and Kevin Braeckmans

10 Infrared Spectroscopy to Characterize Protein Aggregates 227
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 Protein Pharmaceuticals 269
Patrick Garidel, Andrea Herre, and Werner Kliche

III INTEGRATED APPROACHES TO PROTEIN AGGREGATION AND PARTICLES 303

13 Comparison of Methods for Soluble Aggregate Detection and Size Characterization 305
John S. Philo

14 Protein Purification and Its Relation to Protein Aggregation and Particles 335
Roberto Falkenstein, Stefan Hepbildikler, Wolfgang Kuhne, Thorsten Lemm, Hans Rogl, Eva Rosenberg, Gerhard Winter, Frank Zettl, and Ralf Zippelius

15 Formulation Development and Its Relation to Protein Aggregation and Particles 369
Miriam Printz and Wolfgang Friess

Index 389