Drug Safety Evluation
Comprehensive and practical guide presenting a roadmap for safety assessment as an integral part of the development of drugs and therapeutics
This fourth edition of Drug Safety Evaluation maintains the central objective of presenting an all-inclusive practical guide for those who are responsible for ensuring the safety of drugs and biologics to patients, healthcare providers, those involved in the manufacture of medicinal products, and all those who need to understand how the safety of these products is evaluated and shepherding valuable candidates to market.
Individual chapters address specific approaches to evaluation hazards, including problems that are encountered and their solutions. Also covered are the scientific and philosophical bases for evaluation of specific concerns (e.g., carcinogenicity, development toxicity, etc.) to provide both understanding and guidance for approaching the new problems that have come to face both our society and the new challenges they brought.
The many changes in regulatory requirements, pharmaceutical development, technology, and the effects of Covid on our society and science have required both extensive revision to every chapter and the addition of four new chapters.
Specific sample topics covered in Drug Safety Evaluation include:
- The drug development process and the global pharmaceutical marketplace and regulation of human pharmaceutical safety
- Sources of information for consideration in study and program design and in safety evaluation
- Electronic records, reporting and submission, screens in safety and hazard assessment, and formulations, routes, and dosage regimens
- Mechanisms and endpoints of drug toxicity, pilot toxicity testing in drug safety evaluation, and repeat dose toxicity
- Genotoxicity, QSAR tools for drug safety, toxicogenomics, nonrodent animal studies, and developmental and reproductive toxicity testing
- An appendix which provides an up to date guide to CROs for conducting studies
Drug Safety Evaluation was written specifically for the pharmaceutical and biotechnology industries, including scientists, consultants, and academics, to show a utilitarian yet scientifically valid path to the everyday challenges of safety evaluation and the problem solving that is required in drug discovery and development.
Table of Contents
PREFACE xxix
ABOUT THE AUTHORS xxxi
1 The Drug Development Process and The Global Pharmaceutical Marketplace 1
2 Regulation of Human Pharmaceutical Safety: Routes To Human Use and Market 19
3 Data Mining: Sources of Information For Consideration In Study And Program Design and In Safety Evaluation 67
4 Electronic Records, Reporting, and Submission: eCTD and Send 75
5 Screens in Safety and Hazard Assessment 83
6 Formulations, Routes, and Dosage Regimens 95
7 Mechanisms And End Points Of Drug Toxicity 131
8 Pilot Toxicity Testing In Drug Safety Evaluation: MTD and DRF 143
9 Repeat-Dose Toxicity Studies 173
10 Genotoxicity 183
11 QSAR Tools For Drug Safety 223
12 Toxicogenomics 241
13 Immunotoxicology In Drug Development 247
14 Nonrodent Animal Studies 293
15 Developmental And Reproductive Toxicity Testing 331
16 Carcinogenicity Studies 363
17 Histopathology and Clinical Pathology In Nonclinical Pharmaceutical Safety Assessment 395
18 Irritation And Local Tissue Tolerance In Pharmaceutical Safety Assessment 403
19 Pharmacokinetics And Toxicokinetics In Drug Safety Evaluation 425
20 Safety Pharmacology 457
21 Special Concerns For The Preclinical Evaluation Of Biotechnology Products 477
22 Safety Assessment of Inhalant Drugs And Dermal Route Drugs 507
23 Special Case Products: Imaging Agents 529
24 Special Case Products: Drugs For Treatment Of Cancer 535
25 Pediatric Product Safety Assessment (2006 Guidance, Including Juvenile And Pediatric Toxicology) 543
26 Use Of Imaging, Imaging Agents, And Radiopharmaceuticals In Nonclinical Toxicology 551
27 Occupational Toxicology In The Pharmaceutical Industry 571
28 Strategy and Phasing For Nonclinical Drug Safety EvaluationIn The Discovery and Development of Pharmaceuticals 585
29 The Application of In Vitro Techniques In Drug Safety Assessment 603
30 Evaluation Of Human Tolerance And Safety In Clinical Trials: Phase I And Beyond 635
31 Postmarketing Safety Evaluation: Monitoring, Assessing, And Reporting of Adverse Drug Responses (ADRs) 683
32 Statistics In Pharmaceutical Safety Assessment 707
33 Combination Products: Drugs and Devices 767
34 Qualification Of Impurities, Degradants, Residual Solvents, Metals, and Leachables in Pharmaceuticals 777
35 Tissue, Cell, and Gene Therapy 789
36 Adverse Outcome Pathways in Drug Safety Assessment 801
Appendix A: Selected Regulatory and Toxicological Acronyms 805
Appendix B: Definition Of Terms And Lexicon of "Clinical" Observations in Nonclinical (Animal) Studies 807
Appendix C: Notable Regulatory Internet Addresses 811
Appendix D: Glossary Of Terms Used in The Clinical Evaluation of Therapeutic Agents 817
Appendix E: Common Vehicles For The Nonclinical Evaluation of Therapeutic Agents 821
Appendix F: Global Directory of Contract Toxicology Labs 919
INDEX 945
