Biophysical Characterization of Proteins in Developing Biopharmaceuticals

Damian J. Houde is Professor at the Department of Chemistry and Chemical Biology at the Northeastern University in Boston, MA. He teaches undergraduate and graduate level chemistry, biochemistry courses, and bioanalytical biochemistry. Further he is scientist, analytical development at Biogen Idec, Inc. in Cambridge, MA. He performs detailed biochemical and biophysical characterization of protein biopharmaceuticals (primarily monoclonal antibodies and Fc-fusion proteins) for structure activity relationship studies, investigates the conformation, dynamics, and interactions (epitope mapping) of protein biopharmaceuticals, with hydrogen-deuterium exchange mass spectrometry, assesses, develops, and evaluates new biochemical and biophysical protein characterization tools, coordinates and manages external academic (Northeastern University and University of Mass at Amherst) and internal research collaborations, manages and maintains mass spectrometry instrumentation, and conducts method transfers to QC. In 2009 he received the Douglas and Irena DeVivo Award (Northeastern University), in 2008 the Biogen IDEC Technology Investment Award, in 2008 the Biogen IDEC Technology Investment Award, Outstanding presentation, and in 2007 the Biogen IDEC Technology Investment Award Steven A. Berkowitz is a principal investigator in the department of analytical development at Biogen Idec, Inc. in Cambridge MA. His technical areas of expertise are concentrated in the separation sciences and the physical sciences associated with the characterization of biopolymers and synthetic polymers where he has over 40 peer reviewed publication and has presented numerous talks and posters at a wide range of technical meetings. Much of Dr. Berkowitz’s work has centered on assessing the physico-chemical properties, micro-heterogeneity and aggregation properties of biopharmaceuticals using light scattering, analytical ultracentrifugation, chromatography, electrophoresis, and various forms of spectroscopy. His present responsibilities are now focused on providing biophysical information on the higher-order structure and structural dynamics of biopharmaceuticals and the development and evaluation of analytical tools such as H/DX-MS and NMR to support this area. Dr. Berkowitz received a B.S. degree in Biology from Fairleigh Dickinson University and a Ph.D. degree in Biochemistry from New York University. He then spent several years as a post-doctoral fellow at Yale University and the NIH. After his post-doctoral work Dr. Berkowitz held various positions at Celanese Research Company, J.T. Baker, and Lederle Laboratories before taking his present position at Biogen Idec.

List of Contributors About the Editors Preface List of Abbreviations and Symbols

I: Proteins and Biophysical Characterization in the Biopharmaceutical Industry Chapter 1 - The Complexity of Protein Structure and the Challenges it Poses in Developing Biopharmaceuticals (Steven A. Berkowitz, Damian J. Houde) Chapter 2 - Biophysical Characterization and Its Role in the Biopharmaceutical Industry (Damian J. Houde, Steven A. Berkowitz) Chapter 3 - Biopharmaceutical Industry's Biophysical Toolbox (Damian J. Houde, Steven A. Berkowitz)

II: The Selected Biophysical Tools in the Biopharmaceutical Industry Chapter 4 - An Introduction and Hierarchical Organization of the Biophysical Tool in Section II (Damian J. Houde, Steven A. Berkowitz) Chapter 5 - The Value of UV, Fluorescence, and FTIR Spectroscopy in Biopharmaceutical Development (Mark Brader) Chapter 6 - Circular Dichroism Spectroscopy for Protein Characterization: Biopharmaceutical Applications (A.J. Miles, B.A. Wallace) Chapter 7 - Size-Exclusion Chromatograph (SEC) in Biopharmaceutical Process Development (Steven A. Berkowitz, Damian J. Houde) Chapter 8 - Scattering Techniques for the Characterization of Biopharmaceuticals, Pages 171-209, Lee Makowski, Steven A. Berkowitz, Damian J. Houde Chapter 9 - Characterizing Biopharmaceuticals using Analytical Ultracentrifugation (Steven A. Berkowitz, John S. Philo) Chapter 10 - Subvisible and Visible Particle Analysis in Biopharmaceutical Research and Development, Pages 261-286, Andrea Hawe, Sarah Zölls, Angelika Freitag, John F. Carpenter Chapter 11 - Differential Scanning Calorimetry in the Biopharmaceutical Sciences (Stephen J. Demarest, Verna Frasca) Chapter 12 - Biophysical Mass Spectrometry for Biopharmaceutical Process Development: Focus on Hydrogen/Deuterium Exchange (George M. Bou-Assaf, Alan G. Marshall) Chapter 13 - One- and Two-Dimensional NMR Techniques for Biopharmaceuticals (Yves Aubin, Daron I. Freedberg, David A. Keire)

III: Concluding Remarks on the Biophysical Characterization of Biopharmaceuticals Chapter 14 - Biophysical Characterization: An Integral Part of the “Totality of the Evidence” Concept (Damian J. Houde, Steven A. Berkowitz)

Index