Table of Contents
Contributors xiii
Foreword xv
Preface xvii
Preface to the First Edition xix
Acknowledgments xxi
Organization of the Book xxiii
User Agreement xxv
Part I
Transforming Proteins and Genes into Drugs - The Science and the Art 1
1 Introduction to Biopharmaceuticals 3
Abstract 3
1.1 Background and Significance 4
1.2 Translation of Biotechnology for Developing Biopharmaceuticals 7
1.3 Historical Perspective of Pharmaceutical Biotechnology 8
1.4 Distinctions between Chemical Drugs Versus Biopharmaceuticals 8
1.5 Summary 10
2 Distinctions of Biologic Versus Small Molecule Platforms in Drug Development 13
Abstract 13
2.1 Introduction 14
2.2 Transforming New Molecules into Drugs: The Drug Development Process 14
2.3 Key Differences between Biotechnology and Chemical Products 16
2.4 Current Trends in Drug Development 18
2.5 Summary 22
3 Financing Biologic Drug Development 23
Abstract 23
3.1 Introduction 24
3.2 The Role of the Orphan Drug Act 27
3.3 Clinical Leverage Strategy in Accelerating Drug Development 30
3.4 Therapeutic Target Considerations 32
3.5 Evolving Trends 34
3.6 Summary 36
4 Application of Biotechnology in Drug Discovery and Early Development 39
Abstract 39
4.1 Introduction 40
4.2 Data Mining, Molecular Cloning, and Characterization 40
4.3 Optimization of Cell Expression Systems and Product Yield 50
4.4 Molecular Optimization 51
4.5 Proteins and Genes as Targets for Drug Discovery and Development 56
4.6 Summary 58
5 Large-Scale Production of Recombinant Proteins 63
Abstract 63
5.1 Introduction 64
5.2 Yield Optimization in Genetic Constructs and Host Cells 65
5.3 Large-Scale Cultivation of Host Cells 66
5.4 Downstream Processing and Purification 70
5.5 Quality Assurance and Quality Control 75
5.6 Summary 77
6 Clinical Pharmacology, Toxicology, and Therapeutic Dosage and Response 79
Abstract 79
6.1 Introduction 80
6.2 Clinical Pharmacology and Toxicology 80
6.3 Dose and Therapeutic Response 95
6.4 Dosage Form and Route of Administration 97
6.5 Summary 99
7 Clinical Evaluation and Regulatory Approval and Enforcement of Biopharmaceuticals 103
Abstract 103
7.1 Introduction: Biologic Drug Development and Approval 104
7.2 Licensing of Biological Products 104
7.3 Preclinical and Clinical Testing 107
7.4 FDA Review and Approval Process 114
7.5 Regulatory Enforcement 118
7.6 Globalization of Drug Approval (Chien*) 118
7.7 Summary 122
8 Pharmacoeconomics and Drug Pricing (Garrison*) 125
Abstract 125
8.1 Introduction: Pharmacoeconomics 126
8.2 Cost-Effectiveness: Assessing the Value of Biopharmaceuticals 126
8.3 The Cost of Developing Biopharmaceuticals 128
8.4 Pricing Biopharmaceuticals 131
8.5 Drug Development Incentives 133
8.6 Economics of Biosimilars 133
8.7 Economic Impact of Personalized Medicine 134
8.8 Summary and Future Challenges 135
Part II
Therapeutic and Clinical Applications of Biopharmaceu ticals - Proteins and Nucleic Acids 137
9 Antibodies and Derivatives 139
Abstract 139
Section One 140
9.1 Molecular Characteristics and Therapeutic Applications 140
9.1.1 Introduction 140
9.1.2 Historical Perspective - Discovery, Classification, Biodistribution, and Physiological Characteristics of Antibody Molecules 140
9.1.3 Gamma Globulin and Hyperimmune Globulin 144
9.1.4 Monoclonal Antibodies - From Mouse, Mouse-Human Chimeric, Humanized, to Human Monoclonal Antibodies 145
9.1.5 Antibody Derivatives 147
9.1.6 Disposition of Antibodies 149
9.1.7 Extravascular Tissue Penetration 155
9.1.8 Mechanisms of Antibody Bioactivities 156
9.1.9 Antibody Conjugates 156
9.1.10 Antibodies and Derivatives in Development 158
9.1.11 Summary 159
Section Two 162
9.2 Antibodies and Derivatives Monographs List 162
9.3 Antibodies and Derivatives Monographs 163
10 Hematopoietic Growth and Coagulation Factors 211
Abstract 211
Section One 212
10.1 Molecular Characteristics and Therapeutic Applications 212
10.1.1 Introduction 212
10.1.2 Hematopoietic Growth and Coagulation Factors 212
10.1.3 Therapeutic Use of Hematopoietic Growth Factors (Molineux, Elliott*) 218
10.1.4 Therapeutic Use of Coagulation and Anticoagulation Factors 225
10.1.5 Summary 229
Section Two 231
10.2 Hematopoietic Growth and Coagulation Factors List 231
10.3 Hematopoietic Growth and Coagulation Factors Monographs 231
11 Cytokines and Interferons 251
Abstract 251
Section One 252
11.1 Molecular Characteristics and Therapeutic Applications 252
11.1.1 Introduction 252
11.1.2 Interleukins as Immunotherapeutics 252
11.1.3 Interferon Biology and Cancer Therapy (Tiu, Koon, Borden*) 256
11.1.4 Interferons as Antiviral Therapy 271
11.1.5 Interferons in Multiple Sclerosis 275
11.1.6 Summary 280
Section Two 288
11.2 Cytokines and Interferons Monographs List 288
11.3 Cytokines and Interferons Monographs 288
12 Hormones 307
Abstract 307
Section One 308
12.1 Molecular Characteristics and Therapeutic Applications 308
12.1.1 Introduction 308
12.1.2 Peptide Hormones and Clinical Significance 308
12.1.3 Therapeutic Application of Recombinant and
Synthetic Hormones 309
12.1.4 Summary 318
Section Two 320
12.2 Hormones Monographs List 320
12.3 Hormones Monographs 320
13 Enzymes 357
Abstract 357
Section One 358
13.1 Molecular Characteristics and Therapeutic Applications 358
13.1.1 Introduction 358
13.1.2 Enzyme Replacement Therapy 359
13.1.3 Enzymes as Therapeutic Agents 365
13.1.4 Summary and Future Prospects 368
Section Two 370
13.2 Enzymes Monographs List 370
13.3 Enzymes Monographs 370
14 Vaccines (Hu, Ho*) 389
Abstract 389
Section One 390
14.1 Molecular Characteristics and Therapeutic Applications 390
14.1.1 Vaccines and Their Impact on Human Health 390
14.1.2 How Vaccines Work: Interplay among Immune System, Diseases, and Vaccines 393
14.1.3 Traditional Vaccine Approaches 394
14.1.4 Subcellular and Recombinant Subunit Vaccines 395
14.1.5 Vaccine Adjuvants 398
14.1.6 Mode and Route of Vaccine Delivery 400
14.1.7 Future Directions 403
14.1.8 Summary 405
Section Two 409
14.2 Vaccines Monographs List 409
14.3 Vaccines Monographs 409
15 Other Biopharmaceutical Products 417
Abstract 417
15.1 Other Biopharmaceutical Products Monographs List 418
15.2 Other Biopharmaceutical Products Monographs 418
Part III
Future Directions 425
16 Advanced Drug Delivery 427
Abstract 427
16.1 Introduction 428
16.2 Drug Therapeutic Index and Clinical Impact 429
16.3 Routes of Therapeutic Protein Administration 430
16.4 Physiological and Mechanistic Approaches 436
16.5 Approaches Using Devices 458
16.6 Molecular Approaches 460
16.7 Summary 465
17 Advances in Personalized Medicine: Pharmacogenetics in Drug Therapy 471
Abstract 471
17.1 Introduction to Interindividual Variation 472
17.2 Historical Perspective on Pharmacogenetics in Drug Safety and Efficacy 473
17.3 Pharmacogenetics in Drug Disposition and Pharmacokinetics 478
17.4 Pharmacogenetics in Drug Effects and Pharmacodynamics 483
17.5 Individualized Gene-Based Medicine: A Mixed Blessing 487
17.6 Current and Future Prospects of Pharmacogenetics 490
17.7 Summary 492
18 Gene and Cell Therapy 495
Abstract 495
18.1 Overview 496
18.2 General Strategies in Gene and Cell Therapy 499
18.3 Gene and Cell Therapy for Select Medical Conditions 501
18.4 Gene Therapy Research, Development, and Clinical Use (Sullivan*) 506
18.5 Stem Cells in Regenerative Medicine and Diagnostics (Kelly*) 509
18.6 Summary 513
19 Integration of Discovery and Development: The Role of Genomics, Proteomics, and Metabolomics 517
Abstract 517
19.1 Overview 518
19.2 Integration of Discovery and Development of Therapeutic Candidates 520
19.3 Genomics: The First Link between Sequences and Drug Targets 521
19.4 Proteomics: From Sequences to Functions 524
19.5 Metabolomics: Metabolic Profile Elucidation 528
19.6 Integrating Genomic, Proteomic, and Metabolomic Tools to Accelerate Drug Development 530
19.7 Summary 532
20 Pharmacoeconomics, Outcome, and Health Technology Assessment Research in Drug Development 535
Abstract 535
20.1 Introduction: Health-Care Decisions and Health Outcomes 536
20.2 Integration of Pharmacoeconomic Outcome Research in Clinical Drug Development 538
20.3 Regional Differences in the Type of Evidence and Value Data Essential for Health-Care and Reimbursement Decisions 541
20.4 Biopharmaceutical Company Strategies 542
20.5 Summary 545
20.6 Acknowledgments 546
21 Future Prospects 547
Abstract 547
21.1 Progress and Benefits in Transforming Proteins and Genes into Biopharmaceuticals 548
21.2 Genomic Information Improves Safety and Production Cost of Biopharmaceuticals 548
21.3 The Business of Biopharmaceuticals and Economic Impacts 549
21.4 Influence of Biopharmaceuticals on Pharmaceutical Research, Development, and the Drug Industry 549
21.5 Public–Private Partnership in Financial and Regulatory Support to Improve Translational Success 550
21.6 Biopharmaceuticals and Public Health Benefits 551
21.7 Public Participation and Influence on Biopharmaceutical Development 551
21.8 Outlook 552
Appendix I. Dosage Form, Pharmacokinetics, and Disposition Data 555
Appendix II. Molecular Characteristics and Therapeutic Use 581
Appendix III. Nomenclature of Biotechnology Products 617
Appendix IV. Other Information 621
Index 633
Color plate section is located between pages 210 and 211.
