Biophysical Characterization of Proteins in Developing Biopharmaceuticals (eBook)

Steven A. Berkowitz, Damian J. Houde (Herausgeber)

eBook Download: PDF | EPUB

2014 | 1. Auflage
426 Seiten
Elsevier Science (Verlag)
978-0-444-59590-4 (ISBN)

Infos

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.

Inhalt

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

Textauszug

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...

Produkt-Details

• Erscheint lt. Verlag: 5.9.2014
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Gesundheitsfachberufe
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
• Themenwelt: Medizin / Pharmazie ► Pharmazie
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Chemie ► Organische Chemie
• Themenwelt: Naturwissenschaften ► Chemie ► Physikalische Chemie
• Themenwelt: Naturwissenschaften ► Chemie ► Technische Chemie
• Themenwelt: Technik
• Themenwelt: Wirtschaft
• ISBN-10: 0-444-59590-2 / 0444595902
• ISBN-13: 978-0-444-59590-4 / 9780444595904