Houde / Berkowitz Biophysical Characterization of Proteins in Developing Biopharmaceuticals

1. Auflage 2014
ISBN: 978-0-444-59590-4
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 426 Seiten

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. - Presents the reader with a clear understanding of the real world issues and challenges in using these methods. - Highlights the capabilities and limitations of each method. - Discusses how to best analyze the data generated from these methods. - Points out what one needs to look for to avoid making faulty conclusions and mistakes. - In total it provides a check list or road map that empowers the industrial scientists as to what they need to be concerned with in order to effectively do their part in successfully developing these new drugs in an efficient and cost effective manner.

Autoren/Hrsg.

Houde, Damian J.

Berkowitz, Steven A.

Inhaltsverzeichnis

1;Front Cover;1
2;Biophysical Characterization of Proteins in Developing Biopharmaceuticals;4
3;Copyright;5
4;Contents;6
5;List of Contributors;10
6;About the Editors;12
7;Preface;14
8;List of Abbreviations and Symbols;18
9;Chapter 1 - The Complexity of Protein Structure and the Challenges it Poses in Developing Biopharmaceuticals;24
9.1;1.1 THE BASICS OF PROTEIN HIGHER-ORDER STRUCTURE (HOS);24
9.2;1.2 THE SEARCH FOR HOW PROTEINS ATTAIN THEIR CORRECT HOS: THE PROTEIN FOLDING PROBLEM;31
9.3;1.3 SURPRISES IN THE WORLD OF PROTEIN FOLDING: INTRINSICALLY DISORDERED OR UNSTRUCTURED PROTEINS (AN APPARENT CHALLENGE TO THE ...;35
9.4;1.4 PROTEINS AND THE BIOPHARMACEUTICAL INDUSTRY: PROBLEMS AND CHALLENGES;35
9.5;1.5 CONCLUSION;40
9.6;References;41
9.7;Further Reading;44
10;Chapter 2 - Biophysical Characterization and Its Role in the Biopharmaceutical Industry;46
10.1;2.1 DRUG DEVELOPMENT PROCESS;46
10.2;2.2 PROTEIN DRUGS (BIOPHARMACEUTICALS);48
10.3;2.3 THE ROLE OF BIOPHYSICAL CHARACTERIZATION IN BIOPHARMACEUTICAL DRUG DEVELOPMENT;50
10.4;2.4 THE CHALLENGES IN CONDUCTING BIOPHYSICAL MEASUREMENTS TO DETECT CHANGES IN A PROTEIN DRUG'S HOS;62
10.5;2.5 REGULATORY NEEDS AND CONSIDERATIONS;65
10.6;References;66
10.7;Further Reading;70
11;Chapter 3 - Biopharmaceutical Industry's Biophysical Toolbox;72
11.1;3.1 ATTRIBUTES OF A SINGLE BIOPHYSICAL TOOL TO CHARACTERIZE AND DETECT CHANGES IN THE HIGHER ORDER STRUCTURE OF A BIOPHARMACEUTICAL;72
11.2;3.2 STUDYING THE BIOPHYSICAL PROPERTIES OF A BIOPHARMACEUTICAL AS AN INDIRECT APPROACH FOR CHARACTERIZING CHANGES IN ITS HOS;74
11.3;3.3 GENERAL CONSIDERATIONS IN ANALYZING THE BIOPHYSICAL PROPERTIES OF BIOPHARMACEUTICALS;77
11.4;3.4 THE UTILITY OF USING STRESS TO MONITOR CHANGES IN THE HOS PROFILE OF A PROTEIN DRUG;81
11.5;3.5 PRESENT BIOPHYSICAL TOOLBOX;82
11.6;3.6 CONCLUSION;97
11.7;References;97
11.8;Further Reading;101
12;Chapter 4 - An Introduction and Hierarchical Organization of the Biophysical Tool in Section II;102
12.1;4.1 INTRODUCTION;102
12.2;4.2 THE STANDARD CLASS OF BIOPHYSICAL TOOLS USED IN THE BIOPHARMACEUTICAL INDUSTRY;104
12.3;4.3 THE ADVANCED CLASS OF BIOPHYSICAL TOOLS USED IN THE BIOPHARMACEUTICAL INDUSTRY;105
12.4;4.4 AN OVERVIEW OF SECTION II;107
12.5;References;107
12.6;Further Reading;108
13;Chapter 5 - The Value of UV, Fluorescence, and FTIR Spectroscopy in Biopharmaceutical Development;110
13.1;5.1 INTRODUCTION;110
13.2;5.2 THE ORIGINS OF ELECTRONIC ABSORPTION, FLUORESCENCE, AND FT-IR SPECTROSCOPY;111
13.3;5.3 CONFORMATIONAL ANALYSIS OF PROTEINS IN SOLUTION;115
13.4;5.4 OPTICAL SPECTROSCOPY AND PRODUCT COMPARABILITY;118
13.5;5.5 OPTICAL SPECTROSCOPY AND HIGH-THROUGHPUT METHODS;122
13.6;5.6 SOLID-STATE MEASUREMENTS;125
13.7;5.7 CONCLUSIONS;127
13.8;References;128
14;Chapter 6 - Circular Dichroism Spectroscopy for Protein Characterization: Biopharmaceutical Applications;132
14.1;6.1 INTRODUCTION;132
14.2;6.2 INSTRUMENTATION;137
14.3;6.3 DATA GENERATED;138
14.4;6.4 GUIDE TO COLLECTING GOOD DATA;139
14.5;6.5 DATA PROCESSING AND ANALYSES;150
14.6;6.6 ROLE IN THE RESEARCH INDUSTRY;153
14.7;6.7 TECHNOLOGY AVAILABILITY;154
14.8;6.8 FUTURE DEVELOPMENTS;156
14.9;Acknowledgments;157
14.10;References;157
14.11;Further Reading;159
15;Chapter 7 - Size-Exclusion Chromatograph (SEC) in Biopharmaceutical Process Development;162
15.1;7.1 INTRODUCTION;162
15.2;7.2 BASIC THEORY OF NORMAL OR IDEAL SEC;163
15.3;7.3 MAXIMIZING SEC SEPARATION BY ENHANCING THE USAGE OF PORE VOLUME AND PORE STRUCTURE;167
15.4;7.4 CHARACTERISTICS OF PORE STRUCTURE;169
15.5;7.5 NONIDEAL SEC CHROMATOGRAPHY;170
15.6;7.6 ASSESSING AND MAINTAINING AN OPTIMUM SEC CHROMATOGRAPHY METHOD;174
15.7;7.7 DETECTORS;176
15.8;7.8 MULTIDETECTOR SEC;183
15.9;7.9 AGGREGATION;187
15.10;7.10 TECHNOLOGY ADVANCES;188
15.11;7.11 CONCLUSION;188
15.12;References;189
16;Chapter 8 - Scattering Techniques for the Characterization of Biopharmaceuticals;194
16.1;8.1 INTRODUCTION;194
16.2;8.2 INTENSITY- AND TIME-DEPENDENT LIGHT SCATTERING;195
16.3;8.3 GENERAL COMMENT CONCERNING SLS AND DLS;208
16.4;8.4 THE “DUST PROBLEM” IN SLS AND DLS;209
16.5;8.5 X-RAY SCATTERING: CHARACTERIZATION OF PROTEINS IN SOLUTION USING SMALL-ANGLE X-RAY SCATTERING;210
16.6;References;229
17;Chapter 9 - Characterizing Biopharmaceuticals using Analytical Ultracentrifugation;234
17.1;9.1 INTRODUCTION;234
17.2;9.2 UNIQUE FEATURES OF THE ANALYTICAL ULTRACENTRIFUGE THAT MAKE IT DIFFERENT FROM OTHER CENTRIFUGES;235
17.3;9.3 THEORY;236
17.4;9.4 UTILITY OF AUC IN THE BIOPHARMACEUTICAL INDUSTRY;240
17.5;9.5 BOUNDARY SV-AUC;242
17.6;9.6 BAND SV-AUC;262
17.7;9.7 SEDIMENTATION EQUILIBRIUM, SE-AUC;264
17.8;9.8 DENSITY-GRADIENT SE-AUC;266
17.9;9.9 AUC DETECTORS;268
17.10;9.10 MISCELLANEOUS HELPFUL INFORMATION ABOUT CONDUCTING AUC EXPERIMENTS;275
17.11;9.11 CONCLUSION;277
17.12;References;278
17.13;Further Reading;282
18;Chapter 10 - Subvisible and Visible Particle Analysis in Biopharmaceutical Research and Development;284
18.1;10.1 INTRODUCTION;284
18.2;10.2 OVERVIEW OF ANALYTICAL METHODS;285
18.3;10.3 GENERAL RECOMMENDATIONS AND PITFALLS FOR PARTICLE ANALYSIS;302
18.4;10.4 OUTLOOK AND CONCLUSIONS;305
18.5;References;306
19;Chapter 11 - Differential Scanning Calorimetry in the Biopharmaceutical Sciences;310
19.1;11.1 BACKGROUND;310
19.2;11.2 DSC INSTRUMENTS;316
19.3;11.3 PRACTICAL CONSIDERATIONS FOR DSC USE;318
19.4;11.4 DATA ANALYSIS;322
19.5;11.5 APPLICATIONS OF SOLUTION DSC IN BIOPHARMACEUTICAL DISCOVERY AND DEVELOPMENT;323
19.6;11.6 APPLICATIONS OF SOLID-SAMPLE DSC IN BIOPHARMACEUTICAL DISCOVERY AND DEVELOPMENT;325
19.7;11.7 CONCLUSIONS;327
19.8;Acknowledgments;327
19.9;References;327
20;Chapter 12 - Biophysical Mass Spectrometry for Biopharmaceutical Process Development: Focus on Hydrogen/Deuterium Exchange;330
20.1;12.1 INTRODUCTION;330
20.2;12.2 SYNOPSIS OF THE TECHNIQUE;334
20.3;12.3 MECHANISM OF EXCHANGE;335
20.4;12.4 ADVANCES IN THE TECHNIQUE;337
20.5;12.5 COMMERCIALIZATION;345
20.6;12.6 APPLICATIONS IN THE BIOPHARMACEUTICAL INDUSTRY;346
20.7;12.7 FUTURE PERSPECTIVE;353
20.8;Acknowledgments;354
20.9;References;354
21;Chapter 13 - One- and Two-Dimensional NMR
Techniques for Biopharmaceuticals;364
21.1;13.1 PHYSICAL BASIS OF THE TECHNIQUE;364
21.2;13.2 THE APPROPRIATE TECHNIQUE FOR A PARTICULAR PROBLEM;379
21.3;13.3 METHOD REQUIREMENTS AND PERFORMANCE;384
21.4;13.4 DATA PROCESSING (PROCEDURES);396
21.5;13.5 ROLE IN RESEARCH VS PROCESS DEVELOPMENT;398
21.6;13.6 TECHNOLOGY UPDATE: RECENT AND FUTURE ADVANCES AND UNIQUE APPLICATIONS;400
21.7;References;401
21.8;Further Reading;405
22;Chapter 14 - Biophysical Characterization: An Integral Part of the “Totality of the Evidence” Concept;408
22.1;14.1 BIOPHARMACEUTICAL DEVELOPMENT;408
22.2;14.2 AN INTRODUCTION TO THE “TOTALITY OF THE EVIDENCE” AND ITS MORE GLOBAL MEANING IN DEVELOPING BIOPHARMACEUTICALS;409
22.3;14.3 BIOPHYSICAL CHARACTERIZATION IN DEVELOPING PROTEIN BIOPHARMACEUTICALS;411
22.4;14.4 BUILDING A BIOPHARMACEUTICAL'S BIOPHYSICAL FINGERPRINT;412
22.5;14.5 DETECTING SMALL DIFFERENCES IN BIOPHARMACEUTICALS VIA BIOPHYSICAL CHARACTERIZATION MEASUREMENTS;416
22.6;14.6 CONCLUSION;418
22.7;References;418
23;Index;420

Leseproben

List of Abbreviations and Symbols
(T)RPS     (tunable) resistive pulse sensing 3D     three dimensional AC     alternating current ACN     acetonitrile ACS     ammonium camphor sulfonate ADC     analog to digital converter ADCC     antibody dependent cell-mediated cytotoxicity AF4     asymmetric flow field flow fractionation AFM     Atomic force microscopy API     active pharmaceutical ingredient AQL     acceptable quality level ASTM     American Society for Testing and Materials ATR     attenuated total reflectance AUC     analytical ultracentrifugation BLA     biological license application BSA     bovine serum albumin CA     capsid protein CAD     collision-activated dissociation CCD     charge-coupled device CD     circular dichroism cGMP     Current Good Manufacturing Practices CH     immunoglobulin gamma heavy chain constant domain CH1 or CH1     immunoglobulin gamma heavy chain constant domain 1 CH2 or CH2     immunoglobulin gamma heavy chain constant domain 2 CH3 or CH3     immunoglobulin gamma heavy chain constant domain 3 CHO     Chinese hamster ovary CID     collision induced dissociation CL     immunoglobulin gamma light chain constant domain COSY     correlation spectroscopy cP     centipose CPL     circularly polarized light CQA or CQAs     critical quality attribute(s) CSA     camphor sulfonic acid CZE     capillary (free) zone electrophoresis D     deuterium or translational diffusion coefficient DAC     Deutscher Arzneimittel-Codex DC     direct current DLS     dynamic light scattering DoE     design of experiment DP     drug product dPLIMSTEX     dilution PLIMSTEX DRI     differential refractive index detector DS     drug substance DSC     differential scanning calorimetry DSF     differential scanning fluorimetry DSS     4,4-dimethyl-4-silpentane-1-sulfonic acid ECD     electron capture dissociation or equivalent circular diameter EDTA     ethylene diamine tetra-acetic acid EM     electromagnetic radiation EMEA     European Medicines Agency ESD     equivalent sphere diameter ESI     electrospray ionization ESZ     electrical sensing zone ET     electron tomography ETD     electron transfer dissociation EX1     H/D exchange mechanism in which the rate constant for protein folding/unfolding is much slower than the rate constant for H/D exchange EX2     H/D exchange mechanism in which the rate constant for protein folding/unfolding is much faster than the rate constant for H/D exchange Fab     immunoglobulin gamma fragment antigen binding Fc     immunoglobulin gamma fragment crystallizable (constant region) Fc?RIIIa     immunoglobulin gamma Fc receptor RIIIa FDA     Food and Drug Administration FFF     field flow fractionation FID     free induction decay FIX     blood clotting factor IX FL     fluorescence FT-ICR     Fourier transform ion cyclotron resonance FTIR or FT-IR     Fourier transform infrared spectroscopy fuc     fucose FVIII     blood clotting factor VIII gal     galactose GlcNAc     N-acetylglucosamine H/DX-MS or HDX-MS     hydrogen/deuterium exchange mass spectrometry HSA     human serum albumin HCl     hydrochloric acid HDC     hydrodynamic chromatography HDX     hydrogen/deuterium exchange HF5     hollow fiber flow field flow fractionation HGH     human growth hormone HIC     hydrophobic interaction chromatography HILIC     hydrophilic interaction chromatography HMQC     heteronuclear multiple quantum coherence spectroscopy HMW     high molecular weight HOS     higher-order structure HPLC     high performance liquid chromatography HRR-DSC     high ramp rate differential scanning calorimetry HSQC     heteronuclear single quantum coherence spectroscopy HT     high tension HX     hydrogen exchange ICH     international conference on harmonization of technical requirements for registration of pharmaceuticals for human use icIEF     imaging capillary isoelectric focusing IDP     intrinsically disordered protein IDR     intrinsically disordered region IEF     capillary isoelectric focusing IFN     interferon-?1a IgG1     immunoglobulin gamma 1 or immunoglobulin G1 IMS     ion mobility spectrometry ITC     isothermal titration calorimetry IUP     intrinsically unstructured protein IUR     intrinsically unstructured region IV     intravenous injection LC/MS     liquid chromatography/mass spectrometry LMW     low molecular weight LO     light obscuration LOQ     limit of quantitation LS     light scattering mAbs     monoclonal antibodies MALDI     matrix-assisted laser desorption/ionization MALLS     multiangle laser light scattering man     mannose MD     molecular dynamics MEM     maximum entropy method MFI     micro-flow imaging MRE or [M.R.E]     mean residue ellipticity MS     mass spectrometry MS/MS     mass spectrometry/mass spectrometry or tandem mass spectrometry MW     molecular weight NIBS     noninvasive back scattering technique NIST     National Institute of Science and Technology NMR     nuclear magnetic resonance or nuclear magnetic resonance spectroscopy NNLS     nonnegative least squares NOE     Nuclear Overhauser...