Pharmaceutical Development Series: Drug Safety Evaluation
Pharmaceutical Development Series: Drug Safety Evaluation
Editor/Author
Gad, Shayne Cox
Publication Year: 2017
Publisher: Wiley
Single-User Purchase Price:
$350.00

Unlimited-User Purchase Price:
$525.00
ISBN: 978-1-119-09739-6
Category: Health & Medicine - Pharmaceutical Science
Image Count:
135
Book Status: Available
Table of Contents
This practical guide presents a road map for safety assessment as an integral part of the development of new drugs and therapeutics.
This book is found in the following Credo Collections:
Table of Contents
- Acknowledgement
- Preface
- About the Author
- Chapter 1: The Drug Development Process and the Global Pharmaceurical Marketplace
- 1.1 Introduction
- 1.2 The Marketplace
- 1.3 History of Modern Therapeutics
- 1.4 The Drug Development Process
- 1.5 Strategies for Development: Large versus Small Company or the Short versus Long Game
- 1.6 Safety Assessment and the Evolution of Drug Safety
- 1.7 The Three Stages of Drug Safety Evaluation in the General Case
- 1. References
- Chapter 2. Regulation of Human Pharmaceutical Safety
- 2.1 Introduction
- 2.2 Brief History of US Pharmaceutical Law
- 2.3 FDAMA Summary: Consequences and Other Regulations
- 2.4 Overview of US Regulations
- 2.5 Organizations Regulating Drug and Device Safety in the United States
- 2.6 Process of Pharmaceutical Product Development and Approval
- 2.7 Testing Guidelines
- 2.8 Toxicity/Safety Testing: Cellular and Gene Therapy Products
- 2.9 Toxicity Testing: Special Cases
- 2.10 International Pharmaceutical Regulation and Registration
- 2.11 Combination Products
- 2.12 Conclusions
- 2. References
- 2. Further Reading
- Chapter 3. Data Mining
- 3.1 Introduction
- 3.2 PC‐Based Information Products: Laser Disc
- 3.3 Conclusions
- 3. References
- Chapter 4. Screens in Safety and Hazard Assessment
- 4.1 Introduction
- 4.2 Characteristics of Screens
- 4.3 Uses of Screens
- 4.4 Types of Screens
- 4.5 Criterion: Development and Use
- 4.6 Analysis of Screening Data
- 4.7 Univariate Data
- 4. References
- Chapter 5. Formulations, Routes, and Dosage Regimens
- 5.1 Introduction
- 5.2 Mechanisms
- 5.3 Common Routes
- 5.4 Formulation of Test Materials
- 5.5 Dosing Calculations
- 5.6 Calculating Material Requirements
- 5.7 Excipients
- 5. References
- Chapter 6. Nonclinical Manifestations, Mechanisms, and End Points of Drug Toxicity
- 6.1 Introduction
- 6.2 Manifestations
- 6.3 Mechanisms of Toxicity
- 6.4 End Points Measured in General Toxicity Studies
- 6.5 Complications
- 6. References
- Chapter 7. Pilot Toxicity Testing in Drug Safety Evaluation
- 7.1 Introduction
- 7.2 Range‐Finding Studies
- 7.3 Acute Systemic Toxicity Characterization
- 7.4 Screens
- 7.5 Pilot and DRF Studies
- 7. References
- Chapter 8. Repeat‐Dose Toxicity Studies
- 8.1 Introduction
- 8.2 Objectives
- 8.3 Regulatory Considerations
- 8.4 Study Design and Conduct
- 8.5 Study Interpretation and Reporting
- 8. References
- Chapter 9. Genotoxicity
- 9.1 Introduction
- 9.2 ICH Test Profile
- 9.3 DNA Structure
- 9.4 Cytogenics
- 9.5 In Vitro Cytogenic Assays
- 9.6 In Vivo Cytogenic Assays
- 9.7 Sister Chromatid Ecchange Assays
- 9. References
- Chapter 10. QSAR Tools for Drug Safety
- 10.1 Structure–Activity Relationship
- 10.2 SAR Modeling Methods
- 10.3 Applications in Toxicology
- 10.4 Genotoxicity
- 10.5 Comparison of Available Models/Applications
- 10. References
- Chapter 11. Immunotoxicology in Drug Development
- 11.1 Introduction
- 11.2 Overview of the Immune System
- 11.3 Immunotoxic Effects
- 11.4 Immunosuppression
- 11.5 Immunostimulation
- 11.6 Regulatory Positions
- 11.7 Evaluation of the Immune System
- 11.8 Nonspecific Immunity Function Assay
- 11.9 T‐cell‐dependent Antibody Response (TDAR)
- 11.10 Approaches to Compound Evaluation
- 11.11 Problems and Future Directions
- 11. References
- Chapter 12. Nonrodent Animal Studies
- 12.1 Introduction
- 12.2 Comparison Between Rodent and Nonrodent Experimental Design
- 12.3 Differences in Study Activities
- 12.4 Nonrodent Models
- 12.5 Dog
- 12.6 The Ferret
- 12.7 The Pig
- 12.8 Nonhuman Primates
- 12.9 Statistics in Large Animal Studies
- 12.10 Summary
- 12. References
- Chapter 13. Developmental and Reproductive Toxicity Testing
- 13.1 Introduction
- 13.2 ICH Study Designs
- 13.3 Methodological Issues
- 13.4 Developmental Studies in Primates
- 13.5 Data Interpretation
- 13.6 Juvenile and Pediatric Toxicology
- 13.7 In Vitro Tests for Developmental Toxicity
- 13.8 Appraisal of Currrent Approaches for Determining Developmental and Reproductive Hazards
- 13. References
- Chapter 14. Carcinogenicity Studies
- 14.1 Introduction
- 14.2 Mechanisms and Classes of Carcinogens
- 14.3 Genotoxic Carcinogens
- 14.4 Epigenetic Carcinogens
- 14.5 Regulatory Requirements and Timing
- 14.6 Species and Strain
- 14.7 Animal Husbandry
- 14.8 Dose Selection
- 14.9 Group Size
- 14.10 Route of Administration
- 14.11 Study Duration
- 14.12 Survival
- 14.13 End Points Measured
- 14.14 Transgenic Mouse Models
- 14.15 Interpretation of Results: Criteria for a Positive Result
- 14.16 Statistical Analysis
- 14.17 Weight‐of‐Evidence Factors for Consideration in a Carcinogenicity Assessment Document (CAD)
- 14.18 Conclusions
- 14. References
- Chapter 15. Histopathology in Nonclinical Pharmaceutucal Safety Assessment
- 15.1 Introduction
- 15.2 Clinical Pathology
- 15. References
- Chapter 16. Irritation and Local Tissue Tolerance in Pharmaceutucal Safety Assessment
- 16.1 Introduction
- 16.2 Factors Affecting Irritation Responses and Test Outcome
- 16.3 Primary Dermal Irritation (PDI) Test
- 16.4 Other Nonparenteral Route Irritation Tests
- 16.5 Ocular Irritation Testing
- 16.6 Vaginal Irritation
- 16.7 Acute Primary Vaginal Irritation Study in the Female Rabbit
- 16.8 Parenteral Irritation/Tolerance
- 16.9 Problems in Testing (and Their Resolutions)
- 16.10 Phototoxicity
- 16.11 Hemocompatibility
- 16. References
- Chapter 17. Pharmacokinetics and Toxicokinetics in Drug Safety Evaluation
- 17.1 Introduction
- 17.2 Regulations
- 17.3 Principles
- 17.4 Pharmacokinetics
- 17.5 Laboratory Methods
- 17.6 Sampling Methods and Intervals
- 17.7 Study Types
- 17.8 Analysis of Data
- 17.9 Physiologically Based Pharmacokinetic (PBPK) Modeling
- 17.10 Points to Consider
- 17.11 Biologically Derived Materials
- 17.12 Points to Consider
- 17. References
- Chapter 18. Safety Pharmacology
- 18.1 Introduction
- 18.2 Regulatory Requirements
- 18.3 Study Designs and Principles
- 18.4 Organ System‐Specific Tests
- 18.5 Cardiovascular
- 18.6 Central Nervous System
- 18.7 Respiratory/Pulmonary System
- 18.8 Secondary Organ System
- 18.9 Renal Function Tests
- 18.10 Summary
- 18. References
- Chapter 19. Special Concerns for the Preclinical Evaluation of Biotechnology Products
- 19.1 Introduction
- 19.2 Regulation
- 19.3 Preclinical Safety Assessment
- 19.4 Recombinant DNA Technology
- 19.5 Immunogenicity/Allergenicity
- 19.6 Monoclonal Antibody Technology
- 19.7 Bioprocess Technology
- 19.8 Gene Therapy Products
- 19.9 Vaccines
- 19.10 Special Challenges
- 19.11 Planning a Safety Evaluation Program
- 19.12 Challenges: Biosimilars
- 19. References
- Chapter 20. Safety Assessment of Inhalant Drugs and Dermal Route Drugs
- 20.1 Introduction
- 20.2 Inhaled Therapeutics
- 20.3 The Pulmonary System
- 20.4 Penetration and Absorption of Inhaled Gases and Vapors
- 20.5 Deposition of Inhaled Aerosols
- 20.6 Absorption and Clearance of Inhaled Aerosols
- 20.7 Pharmacokinetics and Pharmacodynamics of Inhaled Aerosols
- 20.8 Methods for Safety Assessment of Inhaled Therapeutics
- 20.9 Parameters of Toxicity Evaluation
- 20.10 Inhalation Exposure Techniques
- 20.11 The Utility of Toxicity Data
- 20.12 Formulation and Potential Mucosal Damage
- 20.13 Therapeutic Drug Delivery by the Dermal Route
- 20. References
- Chapter 21. Special Case Products: Imaging Agents
- 21.1 Introduction
- 21.2 Imaging Agents
- 21. References
- Chapter 22. Special Case Products: Drugs for Treatment of Cancer
- 22.1 Introduction
- 22.2 Dose Conversions
- 22. References
- Chapter 23. Pediatric Product Safety Assessment (2006 Guidance, Including Juvenile Toxicology)
- 23.1 Introduction
- 23.2 Issues to Consider Regarding Juvenile Animal Studies
- 23.3 General Considerations in Designing Toxicity Studies in Juvenile Animals
- 23.4 Study Designs and Considerations
- 23. References
- Chapter 24. Use of Imaging, Imaging Agents, and Radiopharmaceuticals in Nonclinical Toxicology
- 24.1 Introduction
- 24.2 X‐ray
- 24.3 Positron Emission Tomography (PET)
- 24.4 Single‐Photon Emission Computed Tomography (SPECT)
- 24.5 Computed Tomography (CT)
- 24.6 Magnetic Resonance Imaging (MRI)
- 24.7 Optical Imaging
- 24.8 Ultrasound
- 24.9 Nanopractice Contrast Agents
- 24.10 Radiopharmaceuticals
- 24.11 Applications of Preclinical Imaging in Laboratory Animals
- 24.12 Nonclinical Safety Assessment for Imaging Agents
- 24.13 Radiopharmaceuticals
- 24.14 Nonclinical Late Radiation Toxicity Studies
- 24.15 Study Design
- 24. References
- Chapter 25. Occupational Toxicology in the Pharmaceutical Industry
- 25.1 Introduction
- 25.2 Occupational Toxicology versus Drug Safety Evaluation
- 25.3 Regulatory Pressures in the United States and the European Community
- 25.4 Organizational Structure
- 25.5 Activities
- 25.6 Conclusion
- 25. References
- Chapter 26. Strategy and Phasing for Nonclinical Drug Safety Evaluation in the Discovery and Development of Pharmaceuticals
- 26.1 Introduction
- 26.2 Regulatory Requirements
- 26.3 Essential Elements of Project Management
- 26.4 Screens: Their Use and Interpretation in Safety Assessment
- 26.5 Strategy and Phasing
- 26.6 Critical Considerations
- 26.7 Special Cases in Safety Assessment
- 26.8 Summary
- 26. References
- Chapter 27. The Application of In Vitro Techniques in Drug Safety Assessment
- 27.1 Introduction
- 27.2 In Vitro Testing in Pharmaceutical Safety Assessment
- 27.3 Defining Testing Objective
- 27.4 Test Systems: Characteristics, Development, and Selection
- 27.5 In Vitro Models
- 27.6 Lethality
- 27.7 In Silico Methods
- 27.8 The Final Frontier and Barrier: Regulatory Acceptance
- 27.9 Summary
- 27. References
- 27. Further Reading
- Chapter 28. Evaluation of Human Tolerance and Safety in Clinical Trials
- 28.1 The Pharmaceutical Clinical Development Process and Safety
- 28.2 Limitations on/of Clinical Trials
- 28.3 The The Clinical Trial Process
- 28.4 Institutional Review Boards (IRBs)/Ethics Committees in the Clinical Trial Process
- 28.5 Drug Formulations and Excipients
- 28.6 Phase I Designs
- 28.7 Clinical Trial Safety Indicators
- 28.8 Assessment of Unwanted Drug Effects
- 28. References
- Chapter 29. Postmarketing Safety Evaluation
- 29.1 Introduction
- 29.2 Causes of Safety Withdrawals
- 29.3 Regulatory Requirements
- 29.4 Management of ADR and ADE Data
- 29.5 Casualty Assessment
- 29.6 Courses of Corrective Action
- 29.7 Legal Consequences of Safety Withdrawal
- 29. References
- Chapter 30. Statistics in Pharmaceutical Safety Assessment
- 30.1 Introduction
- 30.2 Experimental Design
- 30.3 Data Recording
- 30.4 Generalized Methodology Selection
- 30.5 Statistical Alalysis: General Considerations
- 30.6 Hypothesis Testing of Categorical and Ranked Data
- 30.7 Hypothesis Testing: Univariate Parametric Tests
- 30.8 Methods for the Reduction of Dimensionality
- 30.9 Meta‐Analysis
- 30.10 Bayesian Inference
- 30.11 Data Analysis Applications in Safety Assessment Studies
- 30. References
- Chapter 31. Combination Products: Drugs and Devices
- 31.1 Combination Products
- 31. References
- Chapter 32. Qualification of Impurities, Degradants, Residual Solvents, Metals, and Leachables in Pharmaceuticals
- 32.1 Introduction
- 32.2 Impurities
- 32.3 Residual Solvents
- 32.4 Extractables and Leachables
- 32.5 Residual Metals and Elements
- 32. References
- Chapter 33. Tissue, Cell, and Gene Therapy
- 33.1 Introduction
- 33.2 Safety Assessment of Cell Therapy (CT) Products
- 33.3 Nonclinical Safety Assessment of Gene Therapy Products (GTPS)
- 33.4 Definitions
- 33. References
- Appendix A: Selected Regulatory and Toxicological Acronyms
- Appendix B: Definition of Terms and Lexicon of “Clinical” Observations in Nonclinical (Animal) Studies
- Appendix C: Notable Regulatory Internet Addresses
- Appendix D: Glossary of Terms Used in the Clinical Evaluation of Therapeutic Agents
- Appendix E: Common Vehicles for the Nonclinical Evaluation of Therapeutic Agents
- Appendix F: Global Directory of Contract Pharmaceutical Toxicology Labs
- List of Tables
- List of Illustrations