DRUG SAFETY EVALUATION, 3RD EDITION

1 The Drug Development Process and the Global Pharmaceutical Marketplace 1
2 Regulation of Human Pharmaceutical Safety: Routes to Human Use and Market 13
3 Data Mining: Sources of Information for Consideration in Study and Program Design and in Safety Evaluation 59
4 Screens in Safety and Hazard Assessment 67
5 Formulations, Routes, and Dosage Regimens 79
6 Nonclinical Manifestations, Mechanisms, and End Points of Drug Toxicity 115
7 Pilot Toxicity Testing in Drug Safety Evaluation: MTD and DRF 129
8 Repeat-Dose Toxicity Studies 159
9 Genotoxicity 169
10 QSAR Tools for Drug Safety 209
11 Immunotoxicology in Drug Development 225
12 Nonrodent Animal Studies 269
13 Developmental and Reproductive Toxicity Testing 291
14 Carcinogenicity Studies 321
15 Histopathology in Nonclinical Pharmaceutical Safety Assessment 351
16 Irritation and Local Tissue Tolerance in Pharmaceutical Safety Assessment 359
17 Pharmacokinetics and Toxicokinetics in Drug Safety Evaluation 381
18 Safety Pharmacology 413
19 Special Concerns for the Preclinical Evaluation of Biotechnology Products 433
20 Safety Assessment of Inhalant Drugs and Dermal Route Drugs 461
21 Special Case Products: Imaging Agents 483
22 Special Case Products: Drugs for Treatment of Cancer 489
23 Pediatric Product Safety Assessment (2006 Guidance, Including Juvenile Toxicology) 495
24 Use of Imaging, Imaging Agents, and Radiopharmaceuticals in Nonclinical Toxicology 503
25 Occupational Toxicology in the Pharmaceutical Industry 523
26 Strategy and Phasing for Nonclinical Drug Safety Evaluation in the Discovery and Development of Pharmaceuticals 537
27 The Application of In Vitro Techniques in Drug Safety Assessment 553
28 Evaluation of Human Tolerance and Safety in Clinical Trials: Phase I and Beyond 583
29 Postmarketing Safety Evaluation : Monitoring, Assessing, and Reporting of Adverse Drug Responses (ADRs) 629
30 Statistics in Pharmaceutical Safety Assessment 653
31 Combination Products: Drugs and Devices 711
32 Qualification of Impurities, Degradants, Residual Solvents, Metals, and Leachables in Pharmaceuticals 721
33 Tissue, Cell, and Gene Therapy 731

This practical guide presents a road map for safety assessment as an integral part of the development of new drugs and therapeutics.

• Helps readers solve scientific, technical, and regulatory issues in preclinical safety assessment and early clinical drug development
• Explains scientific and philosophical bases for evaluation of specific concerns – including local tissue tolerance, target organ toxicity and carcinogenicity, developmental toxicity, immunogenicity, and immunotoxicity
• Covers the development of new small and large molecules, generics, 505(b)(2) route NDAs, and biosimilars
• Revises material to reflect new drug products (small synthetic, large proteins and cells, and tissues), harmonized global and national regulations, and new technologies for safety evaluation
• Adds almost 20% new and thoroughly updates existing content from the last edition

Author Information
Shayne Cox Gad, BS, PhD, DABT, has more than 39 years of experience in regulatory toxicology, drug and device development, statistics, and risk assessment. He is Principal of Gad Consulting Services, a firm with eight employees and more than 500 clients worldwide in the pharmaceutical and medical device industries. He is Past President of the American College of Toxicology (ACT), the Roundtable of Toxicology Consultants, and three of the Society of Toxicology’s specialty sections. Dr. Gad received the 2008 ACT Lifetime Contribution Award and has authored or edited 47 books (10 with Wley) and more than 350 chapters, articles, and abstracts. Has preparated 110 INDs and 8 NDAs and teaches 3-5 professional education courses a year.