Analysis of Aggregates and Particles in Protein Pharmaceuticals

HANNS-CHRISTIAN MAHLER is Head of Pharmaceutical and Device Development, Pharma Technical Development Biologics Europe at F. Hoffmann-La Roche Ltd. He is also Lecturer at the Institute for Pharmaceutical Technology at the University of Frankfurt/Main, Germany. WIM JISKOOT is Professor and Head of the Biologics Formulation Group in the Leiden/Amsterdam Center for Drug Research (LACDR) at Leiden University.

• Contributors ixPreface xiiiGlossary xv1 The Critical Need for Robust Assays for Quantitation and Characterization of Aggregates ofTherapeutic Proteins 1John F. Carpenter, Barry Cherney, and Amy S. RosenbergI Methods Used for Detecting, Quantifying, and Sizing of Protein Aggregates and Particles 92 Separation-Based Analytical Methods for Measuring Protein Aggregation 11Jun Liu, Barthélemy Demeule, and Steven J. Shire3 Laser Light Scattering-Based Techniques Used for the Characterization of Protein Therapeutics 37John den Engelsman, Fabian Kebbel, and Patrick Garidel4 Online Detection Methods and Emerging Techniques for Soluble Aggregates in ProteinPharmaceuticals 61Tapan K. Das5 Analytical Methods to Measure Subvisible Particulates 85Shawn Cao, Linda Narhi, Yijia Jiang, and Rahul S. Rajan6 Detection of Visible Particles in Parenteral Products 117Ronald Smulders, Hans Vos, and Hanns-Christian Mahler7 Characterization of Aggregates and Particles Using Emerging Techniques 133Hui Zhao, Manuel Diez, Atanas Koulov, Mariola Bozova, Markus Bluemel, and Kurt ForrerII Methods Used to Characterize Protein Aggregates and Particles 1698 Ultraviolet Absorption Spectroscopy 171Reza Esfandiary and Charles Russell Middaugh9 Fluorescence Spectroscopy to Characterize Protein Aggregates and Particles 201Robert A. Poole, Andrea Hawe, Wim Jiskoot, and Kevin Braeckmans10 Infrared Spectroscopy to Characterize Protein Aggregates 227Marco van de Weert and Lene Jørgensen11 Raman Microscopy for Characterization of Particles 249Stefan Fischer, Oliver Valet, and Markus Lankers12 Microscopic Methods for Particle Characterization in Protein Pharmaceuticals 269Patrick Garidel, Andrea Herre, and Werner KlicheIII Integrated Approaches to Protein Aggregation and Particles 30313 Comparison of Methods for Soluble Aggregate Detection and Size Characterization 305John S. Philo14 Protein Purification and Its Relation to Protein Aggregation and Particles 335Roberto Falkenstein, Stefan Hepbildikler, Wolfgang Kuhne, Thorsten Lemm, Hans Rogl, Eva Rosenberg, Gerhard Winter, Frank Zettl, and Ralf Zippelius15 Formulation Development and Its Relation to Protein Aggregation and Particles 369Miriam Printz and Wolfgang FriessIndex 389