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 xxixABOUT THE AUTHORS xxxi1 The Drug Development Process and The Global Pharmaceutical Marketplace 12 Regulation of Human Pharmaceutical Safety: Routes To Human Use and Market 193 Data Mining: Sources of Information For Consideration In Study And Program Design and In Safety Evaluation 674 Electronic Records, Reporting, and Submission: eCTD and Send 755 Screens in Safety and Hazard Assessment 836 Formulations, Routes, and Dosage Regimens 957 Mechanisms And End Points Of Drug Toxicity 1318 Pilot Toxicity Testing In Drug Safety Evaluation: MTD and DRF 1439 Repeat-Dose Toxicity Studies 17310 Genotoxicity 18311 QSAR Tools For Drug Safety 22312 Toxicogenomics 24113 Immunotoxicology In Drug Development 24714 Nonrodent Animal Studies 29315 Developmental And Reproductive Toxicity Testing 33116 Carcinogenicity Studies 36317 Histopathology and Clinical Pathology In Nonclinical Pharmaceutical Safety Assessment 39518 Irritation And Local Tissue Tolerance In Pharmaceutical Safety Assessment 40319 Pharmacokinetics And Toxicokinetics In Drug Safety Evaluation 42520 Safety Pharmacology 45721 Special Concerns For The Preclinical Evaluation Of Biotechnology Products 47722 Safety Assessment of Inhalant Drugs And Dermal Route Drugs 50723 Special Case Products: Imaging Agents 52924 Special Case Products: Drugs For Treatment Of Cancer 53525 Pediatric Product Safety Assessment (2006 Guidance, Including Juvenile And Pediatric Toxicology) 54326 Use Of Imaging, Imaging Agents, And Radiopharmaceuticals In Nonclinical Toxicology 55127 Occupational Toxicology In The Pharmaceutical Industry 57128 Strategy and Phasing For Nonclinical Drug Safety EvaluationIn The Discovery and Development of Pharmaceuticals 58529 The Application of In Vitro Techniques In Drug Safety Assessment 60330 Evaluation Of Human Tolerance And Safety In Clinical Trials: Phase I And Beyond 63531 Postmarketing Safety Evaluation: Monitoring, Assessing, And Reporting of Adverse Drug Responses (ADRs) 68332 Statistics In Pharmaceutical Safety Assessment 70733 Combination Products: Drugs and Devices 76734 Qualification Of Impurities, Degradants, Residual Solvents, Metals, and Leachables in Pharmaceuticals 77735 Tissue, Cell, and Gene Therapy 78936 Adverse Outcome Pathways in Drug Safety Assessment 801Appendix A: Selected Regulatory and Toxicological Acronyms 805Appendix B: Definition Of Terms And Lexicon of "Clinical" Observations in Nonclinical (Animal) Studies 807Appendix C: Notable Regulatory Internet Addresses 811Appendix D: Glossary Of Terms Used in The Clinical Evaluation of Therapeutic Agents 817Appendix E: Common Vehicles For The Nonclinical Evaluation of Therapeutic Agents 821Appendix F: Global Directory of Contract Toxicology Labs 919INDEX 945

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 xxixABOUT THE AUTHORS xxxi1 The Drug Development Process and The Global Pharmaceutical Marketplace 12 Regulation of Human Pharmaceutical Safety: Routes To Human Use and Market 193 Data Mining: Sources of Information For Consideration In Study And Program Design and In Safety Evaluation 674 Electronic Records, Reporting, and Submission: eCTD and Send 755 Screens in Safety and Hazard Assessment 836 Formulations, Routes, and Dosage Regimens 957 Mechanisms And End Points Of Drug Toxicity 1318 Pilot Toxicity Testing In Drug Safety Evaluation: MTD and DRF 1439 Repeat-Dose Toxicity Studies 17310 Genotoxicity 18311 QSAR Tools For Drug Safety 22312 Toxicogenomics 24113 Immunotoxicology In Drug Development 24714 Nonrodent Animal Studies 29315 Developmental And Reproductive Toxicity Testing 33116 Carcinogenicity Studies 36317 Histopathology and Clinical Pathology In Nonclinical Pharmaceutical Safety Assessment 39518 Irritation And Local Tissue Tolerance In Pharmaceutical Safety Assessment 40319 Pharmacokinetics And Toxicokinetics In Drug Safety Evaluation 42520 Safety Pharmacology 45721 Special Concerns For The Preclinical Evaluation Of Biotechnology Products 47722 Safety Assessment of Inhalant Drugs And Dermal Route Drugs 50723 Special Case Products: Imaging Agents 52924 Special Case Products: Drugs For Treatment Of Cancer 53525 Pediatric Product Safety Assessment (2006 Guidance, Including Juvenile And Pediatric Toxicology) 54326 Use Of Imaging, Imaging Agents, And Radiopharmaceuticals In Nonclinical Toxicology 55127 Occupational Toxicology In The Pharmaceutical Industry 57128 Strategy and Phasing For Nonclinical Drug Safety EvaluationIn The Discovery and Development of Pharmaceuticals 58529 The Application of In Vitro Techniques In Drug Safety Assessment 60330 Evaluation Of Human Tolerance And Safety In Clinical Trials: Phase I And Beyond 63531 Postmarketing Safety Evaluation: Monitoring, Assessing, And Reporting of Adverse Drug Responses (ADRs) 68332 Statistics In Pharmaceutical Safety Assessment 70733 Combination Products: Drugs and Devices 76734 Qualification Of Impurities, Degradants, Residual Solvents, Metals, and Leachables in Pharmaceuticals 77735 Tissue, Cell, and Gene Therapy 78936 Adverse Outcome Pathways in Drug Safety Assessment 801Appendix A: Selected Regulatory and Toxicological Acronyms 805Appendix B: Definition Of Terms And Lexicon of "Clinical" Observations in Nonclinical (Animal) Studies 807Appendix C: Notable Regulatory Internet Addresses 811Appendix D: Glossary Of Terms Used in The Clinical Evaluation of Therapeutic Agents 817Appendix E: Common Vehicles For The Nonclinical Evaluation of Therapeutic Agents 821Appendix F: Global Directory of Contract Toxicology Labs 919INDEX 945

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 xxixABOUT THE AUTHORS xxxi1 The Drug Development Process and The Global Pharmaceutical Marketplace 12 Regulation of Human Pharmaceutical Safety: Routes To Human Use and Market 193 Data Mining: Sources of Information For Consideration In Study And Program Design and In Safety Evaluation 674 Electronic Records, Reporting, and Submission: eCTD and Send 755 Screens in Safety and Hazard Assessment 836 Formulations, Routes, and Dosage Regimens 957 Mechanisms And End Points Of Drug Toxicity 1318 Pilot Toxicity Testing In Drug Safety Evaluation: MTD and DRF 1439 Repeat-Dose Toxicity Studies 17310 Genotoxicity 18311 QSAR Tools For Drug Safety 22312 Toxicogenomics 24113 Immunotoxicology In Drug Development 24714 Nonrodent Animal Studies 29315 Developmental And Reproductive Toxicity Testing 33116 Carcinogenicity Studies 36317 Histopathology and Clinical Pathology In Nonclinical Pharmaceutical Safety Assessment 39518 Irritation And Local Tissue Tolerance In Pharmaceutical Safety Assessment 40319 Pharmacokinetics And Toxicokinetics In Drug Safety Evaluation 42520 Safety Pharmacology 45721 Special Concerns For The Preclinical Evaluation Of Biotechnology Products 47722 Safety Assessment of Inhalant Drugs And Dermal Route Drugs 50723 Special Case Products: Imaging Agents 52924 Special Case Products: Drugs For Treatment Of Cancer 53525 Pediatric Product Safety Assessment (2006 Guidance, Including Juvenile And Pediatric Toxicology) 54326 Use Of Imaging, Imaging Agents, And Radiopharmaceuticals In Nonclinical Toxicology 55127 Occupational Toxicology In The Pharmaceutical Industry 57128 Strategy and Phasing For Nonclinical Drug Safety EvaluationIn The Discovery and Development of Pharmaceuticals 58529 The Application of In Vitro Techniques In Drug Safety Assessment 60330 Evaluation Of Human Tolerance And Safety In Clinical Trials: Phase I And Beyond 63531 Postmarketing Safety Evaluation: Monitoring, Assessing, And Reporting of Adverse Drug Responses (ADRs) 68332 Statistics In Pharmaceutical Safety Assessment 70733 Combination Products: Drugs and Devices 76734 Qualification Of Impurities, Degradants, Residual Solvents, Metals, and Leachables in Pharmaceuticals 77735 Tissue, Cell, and Gene Therapy 78936 Adverse Outcome Pathways in Drug Safety Assessment 801Appendix A: Selected Regulatory and Toxicological Acronyms 805Appendix B: Definition Of Terms And Lexicon of "Clinical" Observations in Nonclinical (Animal) Studies 807Appendix C: Notable Regulatory Internet Addresses 811Appendix D: Glossary Of Terms Used in The Clinical Evaluation of Therapeutic Agents 817Appendix E: Common Vehicles For The Nonclinical Evaluation of Therapeutic Agents 821Appendix F: Global Directory of Contract Toxicology Labs 919INDEX 945