Biophysical Characterization of Proteins in Developing Biopharmaceuticals

1st Edition - September 5, 2014
Editors: Damian J. Houde, Steven A. Berkowitz
Language: English
Paperback ISBN:
9 7 8 - 0 - 4 4 4 - 6 3 8 1 0 - 6
Hardback ISBN:
9 7 8 - 0 - 4 4 4 - 5 9 5 7 3 - 7
eBook ISBN:
9 7 8 - 0 - 4 4 4 - 5 9 5 9 0 - 4

Biophysical Characterization of Proteins in Developing Biopharmaceuticals is concerned with the analysis and characterization of the higher-order structure (HOS) or conformat… Read more

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Biophysical Characterization of Proteins in Developing Biopharmaceuticals is concerned with the analysis and characterization of the higher-order structure (HOS) or conformation of protein based drugs. Starting from the very basics of protein structure this book takes the reader on a journey on how to best achieve this goal using the key relevant and practical methods commonly employed in the biopharmaceutical industry today as well as up and coming promising methods that are now gaining increasing attention.

As a general resource guide this book has been written with the intent to help today’s industrial scientists working in the biopharmaceutical industry or the scientists of tomorrow who are planning a career in this industry on how to successfully implement these biophysical methodologies. In so doing a keen focus is placed on understanding the capability of these methodologies in terms of what information they can deliver. Aspects of how to best acquire this biophysical information on these very complex drug molecules, while avoiding potential pitfalls, in order to make concise, well informed productive decisions about their development are key points that are also covered.

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
  - 1.1. The Basics of Protein Higher-Order Structure (HOS)
  - 1.2. The Search for How Proteins Attain Their Correct HOS: The Protein Folding Problem
  - 1.3. Surprises in the World of Protein Folding: Intrinsically Disordered or Unstructured Proteins (An Apparent Challenge to the Protein Structure–Function Paradigm)
  - 1.4. Proteins and the Biopharmaceutical Industry: Problems and Challenges
  - 1.5. Conclusion
- Chapter 2. Biophysical Characterization and Its Role in the Biopharmaceutical Industry
  - 2.1. Drug Development Process
  - 2.2. Protein Drugs (Biopharmaceuticals)
  - 2.3. The Role of Biophysical Characterization in Biopharmaceutical Drug Development
  - 2.4. The Challenges in Conducting Biophysical Measurements to Detect Changes in a Protein Drug's HOS
  - 2.5. Regulatory Needs and Considerations
- Chapter 3. Biopharmaceutical Industry’s Biophysical Toolbox
  - 3.1. Attributes of a Single Biophysical Tool to Characterize and Detect Changes in the Higher Order Structure of a Biopharmaceutical
  - 3.2. Studying the Biophysical Properties of a Biopharmaceutical as an Indirect Approach for Characterizing Changes in its HOS
  - 3.3. General Considerations in Analyzing the Biophysical Properties of Biopharmaceuticals
  - 3.4. The Utility of Using Stress to Monitor Changes in the HOS Profile of a Protein Drug
  - 3.5. Present Biophysical Toolbox
  - 3.6. Conclusion
II. The Selected Biophysical Tools in the Biopharmaceutical Industry
- Chapter 4. An Introduction and Hierarchical Organization of the Biophysical Tool in Section II
  - 4.1. Introduction
  - 4.2. The Standard Class of Biophysical Tools Used in the Biopharmaceutical Industry
  - 4.3. The Advanced Class of Biophysical Tools Used in the Biopharmaceutical Industry
  - 4.4. An Overview of Section II
- Chapter 5. The Value of UV, Fluorescence, and FTIR Spectroscopy in Biopharmaceutical Development
  - 5.1. Introduction
  - 5.2. The Origins of Electronic Absorption, Fluorescence, and FT-IR Spectroscopy
  - 5.3. Conformational Analysis of Proteins in Solution
  - 5.4. Optical Spectroscopy and Product Comparability
  - 5.5. Optical Spectroscopy and High-throughput Methods
  - 5.6. Solid-State Measurements
  - 5.7. Conclusions
- Chapter 6. Circular Dichroism Spectroscopy for Protein Characterization: Biopharmaceutical Applications
  - 6.1. Introduction
  - 6.2. Instrumentation
  - 6.3. Data Generated
  - 6.4. Guide to Collecting Good Data
  - 6.5. Data Processing and Analyses
  - 6.6. Role in the Research Industry
  - 6.7. Technology Availability
  - 6.8. Future Developments
- Chapter 7. Size-Exclusion Chromatograph (SEC) in Biopharmaceutical Process Development
  - 7.1. Introduction
  - 7.2. Basic Theory of Normal or Ideal SEC
  - 7.3. Maximizing Sec Separation By Enhancing The Usage Of Pore Volume and Pore Structure
  - 7.4. Characteristics of Pore Structure
  - 7.5. Nonideal SEC Chromatography
  - 7.6. Assessing and Maintaining an Optimum SEC Chromatography Method
  - 7.7. Detectors
  - 7.8. Multidetector SEC
  - 7.9. Aggregation
  - 7.10. Technology Advances
  - 7.11. Conclusion
- Chapter 8. Scattering Techniques for the Characterization of Biopharmaceuticals
  - 8.1. Introduction
  - 8.2. Intensity- and Time-Dependent Light Scattering
  - 8.3. General Comment Concerning SLS and DLS
  - 8.4. The “Dust Problem” in SLS and DLS
  - 8.5. X-Ray Scattering: Characterization of Proteins in Solution Using Small-Angle X-Ray Scattering
- Chapter 9. Characterizing Biopharmaceuticals using Analytical Ultracentrifugation
  - 9.1. Introduction
  - 9.2. Unique Features of the Analytical Ultracentrifuge That Make It Different from Other Centrifuges
  - 9.3. Theory
  - 9.4. Utility of AUC in the Biopharmaceutical Industry
  - 9.5. Boundary SV-AUC
  - 9.6. Band SV-AUC
  - 9.7. Sedimentation Equilibrium, SE-AUC
  - 9.8. Density-Gradient SE-AUC
  - 9.9. AUC Detectors
  - 9.10. Miscellaneous Helpful Information About Conducting AUC Experiments
  - 9.11. Conclusion
- Chapter 10. Subvisible and Visible Particle Analysis in Biopharmaceutical Research and Development
  - 10.1. Introduction
  - 10.2. Overview of Analytical Methods
  - 10.3. General Recommendations and Pitfalls for Particle Analysis
  - 10.4. Outlook and Conclusions
- Chapter 11. Differential Scanning Calorimetry in the Biopharmaceutical Sciences
  - 11.1. Background
  - 11.2. DSC Instruments
  - 11.3. Practical Considerations for DSC Use
  - 11.4. Data Analysis
  - 11.5. Applications of Solution DSC in Biopharmaceutical Discovery and Development
  - 11.6. Applications of Solid-Sample DSC in Biopharmaceutical Discovery and Development
  - 11.7. Conclusions
- Chapter 12. Biophysical Mass Spectrometry for Biopharmaceutical Process Development: Focus on Hydrogen/Deuterium Exchange
  - 12.1. Introduction
  - 12.2. Synopsis of the Technique
  - 12.3. Mechanism of Exchange
  - 12.4. Advances in the Technique
  - 12.5. Commercialization
  - 12.6. Applications in the Biopharmaceutical Industry
  - 12.7. Future Perspective
- Chapter 13. One- and Two-Dimensional NMR Techniques for Biopharmaceuticals
  - 13.1. Physical Basis of the Technique
  - 13.2. The Appropriate Technique for a Particular Problem
  - 13.3. Method Requirements and Performance
  - 13.4. Data Processing (Procedures)
  - 13.5. Role in Research vs Process Development
  - 13.6. Technology Update: Recent and Future Advances and Unique Applications
III. Concluding Remarks on the Biophysical Characterization of Biopharmaceuticals
- Chapter 14. Biophysical Characterization: An Integral Part of the “Totality of the Evidence” Concept
  - 14.1. Biopharmaceutical Development
  - 14.2. An Introduction to the “Totality of the Evidence” and Its More Global Meaning in Developing Biopharmaceuticals
  - 14.3. Biophysical Characterization in Developing Protein Biopharmaceuticals
  - 14.4. Building a Biopharmaceutical's Biophysical Fingerprint
  - 14.5. Detecting Small Differences in Biopharmaceuticals via Biophysical Characterization Measurements
  - 14.6. Conclusion
Index

Damian J. Houde

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

Affiliations and expertise

Relay Therapeutics, Cambridge, MA, USA and Department of Chemistry and Chemical Biology at the Northeastern University, Boston, MA, USA

Steven A. Berkowitz

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.

Affiliations and expertise

Consultant, Sudbury, MA, USA

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