Analysis of Aggregates and Particles in Protein Pharmaceuticals

Informationen zum Autor 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. Klappentext This book describes how to address the analysis of aggregates and particles in protein pharmaceuticals, provides a comprehensive overview of current methods and integrated approaches used to quantify and characterize aggregates and particles, and discusses regulatory requirements. Analytical methods covered in the book include separation, light scattering, microscopy, and spectroscopy. Zusammenfassung This book describes how to address the analysis of aggregates and particles in protein pharmaceuticals, provides a comprehensive overview of current methods and integrated approaches used to quantify and characterize aggregates and particles, and discusses regulatory requirements. Inhaltsverzeichnis Contributors ixPreface xiiiGlossary xv1 The Critical Need for Robust Assays for Quantitation and Characterization of Aggregates of Therapeutic 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, Barthelemy 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 Protein Pharmaceuticals 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...

Autorentext
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.

Klappentext
Enables researchers to better detect, measure, and characterize aggregates and particles during protein drug development Featuring contributions from leading pharmaceutical investigators around the world, this text enables researchers to choose the most appropriate analytical methods in order to detect and characterize the full spectrum of protein aggregates and particles that can be present in a protein pharmaceutical. Moreover, the authors provide detailed examples of how these methods can be applied during both process and formulation development, helping researchers better manage the problem of protein instability as they seek to develop protein drugs. The text begins with an introduction to aggregates and particles, focusing on their potential immunogenicity. Next, it covers: Methods to detect and measure soluble aggregates based on separation, light scattering, and new technology Methods to detect and measure insoluble aggregates and both sub-visible and visible particles Spectroscopic techniques such as UV/VIS, fluorescence, infrared and Raman spectroscopy, and microscopy to characterize aggregates and particles, elucidate their structures, and identify proteinaceous and non-proteinaceous particles Comparative advantages and disadvantages of the methods for protein aggregate analysis * Approaches for managing aggregates and particles found during protein purification and formulation development Throughout the text, case studies help researchers deal with the challenges that arise in detecting and analyzing protein aggregates and particles. Protein pharmaceuticals are increasingly used to treat life-threatening and chronic diseases, including cancer, viral infections, metabolic disorders, and central nervous system diseases. With Analysis of Aggregates and Particles in Protein Pharmaceuticals as their guide, pharmaceutical researchers now have an important tool in overcoming the challenging problem of aggregates and particles in protein drug development.

Zusammenfassung
This book describes how to address the analysis of aggregates and particles in protein pharmaceuticals, provides a comprehensive overview of current methods and integrated approaches used to quantify and characterize aggregates and particles, and discusses regulatory requirements. Analytical methods covered in the book include separation, light scattering, microscopy, and spectroscopy.

Inhalt

Contributors ix 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 AND PARTICLES 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 Wer…