Drug Safety Evaluation (eBook)

Shayne Cox Gad, PhD, DABT is the Principal of Gad Consulting Services. He has more than 47 years of experience as a toxicologist, statistical consultant, manager, and consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He has successfully file 138 INDs and authored and edited 52 books, as well as numerous papers, presentations, and other publications. Dexter W. Sullivan, Jr., MS, DABT is Senior Toxicologist at Gad Consulting Services.

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