Drugs

The third edition of this best-selling book continues to offer a user-friendly, step-by-step introduction to all the key processes involved in bringing a drug to the market, including the performance of pre-clinical studies, the conduct of human clinical trials, regulatory controls, and even the manufacturing processes for pharmaceutical products. Concise and easy to read, Drugs: From Discovery to Approval, Third Edition quickly introduces basic concepts, then moves on to discuss target selection and the drug discovery process for both small and large molecular drugs. The third edition incorporates the latest developments and updates in the pharmaceutical community, provides more comprehensive coverage of topics, and includes more materials and case studies suited to college and university use. Biotechnology is a dynamic field with changes across R&D, clinical trials, manufacturing and regulatory processes, and the third edition of the text provides timely updates for those in this rapidly growing field.

The third edition of this best-selling book continues to offer a user-friendly, step-by-step introduction to all the key processes involved in bringing a drug to the market, including the performance of pre-clinical studies, the conduct of human clinical trials, regulatory controls, and even the manufacturing processes for pharmaceutical products.Concise and easy to read, Drugs: From Discovery to Approval, Third Edition quickly introduces basic concepts, then moves on to discuss target selection and the drug discovery process for both small and large molecular drugs. The third edition incorporates the latest developments and updates in the pharmaceutical community, provides more comprehensive coverage of topics, and includes more materials and case studies suited to college and university use. Biotechnology is a dynamic field with changes across R&D, clinical trials, manufacturing and regulatory processes, and the third edition of the text provides timely updates for those in this rapidly growing field.

PREFACE TO THE THIRD EDITION xv1 INTRODUCTION 11.1 Aim of this Book 11.2 An Overview of the Drug Discovery to Approval Process 21.3 The Pharmaceutical Industry 61.4 Economics of Drug Discovery and Development 111.5 Trends in Drug Discovery and Development 131.6 Case Study #1.1 151.7 Case Study #1.2 171.8 Summary of Important Points 201.9 Review Questions 201.10 Brief Answers and Explanations 211.11 Further Reading 222 DRUG DISCOVERY: TARGETS AND RECEPTORS 232.1 Drug Discovery Processes 232.2 Medical Needs 242.3 Target Identification 262.4 Target Validation 342.5 Drug Interactions with Targets or Receptors 372.6 Enzymes 402.7 Receptors and Signal Transduction 432.8 Assay Development 522.9 Case Study #2.1 522.10 Case Study #2.2 532.11 Summary of Important Points 572.12 Review Questions 582.13 Brief Answers and Explanations 582.14 Further Reading 593 DRUG DISCOVERY: SMALL MOLECULE DRUGS 613.1 Introduction 613.2 Irrational Approach 623.3 Rational Approach 673.4 Antisense Approach 853.5 RNA Interference Approach 883.6 Chiral Drugs 913.7 Closing Remarks 923.8 Case Study #3.1 943.9 Case Study #3.2 963.10 Summary of Important Points 983.11 Review Questions 993.12 Brief Answers and Explanations 993.13 Further Reading 1004 DRUG DISCOVERY: LARGE MOLECULE DRUGS 1034.1 Introduction 1034.2 Vaccines 1054.3 Antibodies 1174.4 Cytokines 1284.5 Hormones 1344.6 Gene Therapy 1374.7 Stem Cells and Cell Therapy 1394.8 Case Study #4.1 1414.9 Case Study #4.2 1444.10 Summary of Important Points 1464.11 Review Questions 1474.12 Brief Answers and Explanations 1484.13 Further Reading 1485 DRUG DEVELOPMENT AND PRECLINICAL STUDIES 1515.1 Introduction 1515.2 Pharmacodynamics (PD) 1545.3 Pharmacokinetics (PK) 1585.4 Toxicology 1685.5 Animal Tests, In Vitro Assays, and In Silico Methods 1725.6 Formulations and Delivery Systems 1755.7 Nanotechnology 1835.8 Case Study #5.1 1845.9 Case Study #5.2 1855.10 Summary of Important Points 1875.11 Review Questions 1885.12 Brief Answers and Explanations 1885.13 Further Reading 1896 CLINICAL TRIALS 1916.1 Definition of Clinical Trial 1916.2 Ethical Considerations 1926.3 Clinical Trials 1956.4 Regulatory Requirements for Clinical Trials 2046.5 Clinical Data Management 2156.6 Role of Regulatory Authorities 2186.7 Gene Therapy Clinical Trial 2186.8 Adaptive Clinical Trial 2206.9 Meta-Analysis 2216.10 Case Study #6.1 2226.11 Case Study #6.2 2266.12 Summary of Important Points 2276.13 Review Questions 2286.14 Brief Answers and Explanations 2286.15 Further Reading 2297 REGULATORY AUTHORITIES 2317.1 Role of Regulatory Authorities 2317.2 US Food and Drug Administration 2337.3 European Medicines Agency 2367.4 Japan's Pharmaceuticals and Medical Devices Agency (PMDA) 2387.5 China Food and Drug Administration 2407.6 India's Central Drugs Standard Control Organization 2407.7 Australia's Therapeutic Goods Administration 2417.8 Canada's Health Canada 2437.9 Other Regulatory Authorities 2437.10 Authorities Other Than Drug Regulatory Agencies 2437.11 International Conference on Harmonization 2447.12 World Health Organization 2457.13 Pharmaceutical Inspection Cooperation Scheme 2467.14 Case Study # 7.1 2467.15 Case Study # 7.2 2497.16 Summary of Important Points 2507.17 Review Questions 2517.18 Brief Answers and Explanations 2517.19 Further Reading 2528 REGULATORY APPLICATIONS 2538.1 Introduction 2538.2 United States 2548.3 European Union 2728.4 Japan 2808.5 China 2828.6 India 2878.7 Australia 2878.8 Canada 2878.9 Case Study #8.1 2908.10 Case Study #8.2 2928.11 Summary of Important Points 2948.12 Review Questions 2998.13 Brief Answers and Explanations 2998.14 Further Reading 3009 GOOD MANUFACTURING PRACTICE: REGULATORY REQUIREMENTS 3019.1 Introduction 3019.2 United States 3029.3 Europe 3089.4 International Conference on Harmonization (ICH) 3099.5 Pharmaceutical Inspection Cooperation Scheme (PIC/S) 3119.6 Selected Core Elements of GMP 3129.7 Selected GMP Systems 3359.8 New cGMP Initiatives 3509.9 Case Study #9.1 3529.10 Case Study #9.2 3589.11 Summary of Important Points 3629.12 Review Questions 3639.13 Brief Answers and Explanations 3639.14 Further Reading 36410 GOOD MANUFACTURING PRACTICE: DRUG MANUFACTURING 36710.1 Introduction 36710.2 GMP Manufacturing 37110.3 GMP Inspection 37210.4 Manufacture of Small Molecule APIs (Chemical Synthesis Methods) 37910.5 Manufacture of Large Molecule APIs (Recombinant DNA Methods) 38510.6 Finished Dosage Forms 39410.7 Product Quality Review 39810.8 Manufacturing Variations 39910.9 Case Study #10.1 40010.10 Case Study #10.2 40410.11 Summary of Important Points 40710.12 Review Questions 40810.13 Brief Answers and Explanations 40810.14 Further Reading 40811 FUTURE PERSPECTIVES 41111.1 Past Advances and Future Challenges 41111.2 Small Molecule Pharmaceutical Drugs 41211.3 Large Molecule Biopharmaceutical Drugs 41411.4 Traditional Medicine 41411.5 Personalized Medicine 41911.6 Gene Therapy 42011.7 Cloning and Stem Cells 42011.8 Old Age Diseases and Aging 42311.9 Lifestyle Drugs 42311.10 Performance-Enhancing Drugs 42811.11 Chemical and Biological Terrorism 42811.12 Transgenic Animals and Plants 43211.13 Antibiotics Drug Resistance 43311.14 Regulatory Issues 43511.15 Intellectual Property Rights and Marketing Exclusivities 43711.16 Bioethics 44011.17 Concluding Remarks 44211.18 Case Study #11.1 44511.19 Case Study #11.2 44711.20 Further Reading 449APPENDIX 1 HISTORY OF DRUG DISCOVERY AND DEVELOPMENT 451A1.1 Early History of Medicine 451A1.2 Drug Discovery and Development in the Middle Ages 453A1.3 Foundation of Current Drug Discovery and Development 454A1.4 Beginnings of Modern Pharmaceutical Industry 454A1.5 Evolution of Drug Products 455A1.6 Further Reading 456APPENDIX 2 CELLS, NUCLEIC ACIDS, GENES, AND PROTEINS 457A2.1 Cells 457A2.2 Nucleic Acids 460A2.3 Genes and Proteins 462A2.4 Further Reading 468APPENDIX 3 SELECTED DRUGS AND THEIR MECHANISMS OF ACTION 469APPENDIX 4 A DHFR PLASMID VECTOR 481APPENDIX 5 VACCINE PRODUCTION METHODS 483APPENDIX 6 VACCINES APPROVED BY FDA 485APPENDIX 7 PHARMACOLOGY/TOXICOLOGY REVIEW FORMAT 489APPENDIX 8 EXAMPLES OF GENERAL BIOMARKERS 495APPENDIX 9 TOXICITY GRADING 499APPENDIX 10 HEALTH SYSTEMS IN SELECTED COUNTRIES 505ACRONYMS 509GLOSSARY 515INDEX 519