Drug Discovery and Development

Technology in Transition

3rd Edition - August 24, 2021
Editors: Raymond G Hill, Duncan Richards
Language: English
Paperback ISBN:
9 7 8 - 0 - 7 0 2 0 - 7 8 0 4 - 0

Essential insight into drug development and the pharmaceutical industry With unprecedented interest in the power that the modern therapeutic armamentarium has to combat disease,… Read more

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Essential insight into drug development and the pharmaceutical industry

With unprecedented interest in the power that the modern therapeutic armamentarium has to combat disease, the new edition of Drug Discovery and Development is an essential resource for anyone interested in understanding how drugs and other therapeutic interventions are discovered and developed, through to clinical research, registration, and market access.

The text has been thoroughly updated, with new information on biopharmaceuticals and vaccines as well as clinical development and target identification. Drug discovery and development continues to evolve rapidly and this new edition reflects important changes in the landscape.

Edited by industry experts Raymond Hill and Duncan Richards, this market-leading text is suitable for undergraduates and graduates undertaking degrees in pharmacy, pharmacology, toxicology, and clinical development through to those embarking on a career in the pharmaceutical industry.

Cover image
Title page
Table of Contents
Copyright
Preface to 3rd edition
Preface to 2nd edition
Preface to 1st edition
Contributors
List of Tables
List of Illustrations
Section 1. Introduction and background
1. The development of the pharmaceutical industry
Antecedents and origins
Therapeutics in the 18th–19th centuries
An industry begins to emerge
Concluding remarks
References
2. The nature of disease and the purpose of therapy
Introduction
Concepts of disease
The aims of therapeutics
Function and dysfunction: The biological perspective
Therapeutic interventions
Measuring therapeutic outcome
Pharmacoepidemiology and pharmacoeconomics
Summary
References
3. Therapeutic modalities
Introduction
The range of therapeutic interventions
Conventional therapeutic drugs
Biological products
Gene therapy
Other therapeutic approaches
Summary
Further reading
Classic papers on phage display
Nucleotide therapy for neurodegenerative disease
A forward look for CAR-T therapy
Gene therapy overview
CRISPR review
Section 2. Drug discovery
4. Target selection
Introduction
General characteristics of drug targets
Target identification
Use of genetics for target identification
Expression data of the target in tissues
Utilizing systematic literature searches to identify new targets
Tractability assessment
Experimental validation of potential new targets
Understanding target mechanism of action
Clinical context
References
5. From drug target to drug discovery
Introduction
Key project selection criteria
Target product profile
Planning the project
Assay development
Hit/lead identification
Lead optimization
Target validation and biological studies
6. High-throughput screening
Introduction: A historical and future perspective
Lead discovery and high-throughput screening
Screening libraries and compound logistics
Profiling
References
7. The role of medicinal chemistry in the drug discovery process
Introduction
Target selection and validation
Lead identification/generation
Lead optimization
Addressing attrition
Summary
References
8. Therapeutic antibodies
Introduction:
Therapeutic antibody discovery
Antibody fragments, bispecific and alternative formats
Manufacture, biological and biophysical assessment of therapeutic antibodies
Future perspective
References
9. Emerging modalities: Nucleotide-based therapies, cell-based therapies, gene therapy
Introduction
Antisense oligonucleotides and small interfering RNA
Approved oligonucleotide drugs
Cell therapy
TCR-T and CAR T-cell manufacture
TCR-T and CAR T-cell clinical trial outcomes
Gene therapy
Conclusions
References
10. Metabolism and pharmacokinetic optimization strategies in drug discovery
Introduction
Optimization of DMPK properties
Absorption and oral bioavailability
Avoidance of PK-based drug–drug interactions
Central nervous system
Clearance optimization
Optimization of metabolic clearance
Optimization of renal clearance
Optimization of biliary clearance
Cautions
Role of metabolite identification studies in optimization
Active metabolites
Tactics
Minimizing risk for reactive metabolites during drug discovery
Human pharmacokinetics and dose prediction
Summary
Acknowledgements
References
11. Pharmacology
Introduction
Overview
Pharmacological evaluation
Pharmacological profiling in vitro
Good laboratory practice compliance in pharmacological studies
Pharmacology in the development phase
Modelling and simulation and model-based drug development
References
12. Nonclinical safety assessment
Nonclinical package to support first-in-human studies
Primary and secondary pharmacology
Safety pharmacology
Toxicology
Special tests
Reproductive toxicology
Carcinogenicity
Toxicology studies to support use in children
Specific considerations for biopharmaceuticals and advanced therapies
The future—new approaches in translational toxicology
References
Further reading
13. Therapeutic vaccines
Introduction
Vectors, adjuvants and delivery systems
Therapeutic vaccines for infectious diseases
Therapeutic cancer vaccines
Therapeutic vaccines for other chronic diseases
References
Section 3. Drug development
14. An introduction to drug development
Introduction
The nature of drug development
Components of drug development
The interface between discovery and development
Decision points
The need for improvement
Further reading
15. Clinical assessment of safety
Safety assessment in early clinical trials
Phase II
Phase III studies
The summary of product characteristics
Postmarketing surveillance
Further reading
16. Pharmaceutical development
Introduction
Preformulation studies
Routes of administration and dosage forms
Formulation
Principles of drug delivery systems
Summary
References
17. Clinical development
Introduction
Question-based drug development
Phase I: Clinical pharmacology
Phase II studies
Phase III development
Phase IV
Paediatric drug development
Phase 0 (microdose) studies
The future and adaptive pathways
Further reading
18. Clinical imaging in drug development
Introduction
Imaging methods
Human target validation
Biodistribution
Target interaction
Pharmacodynamics
Early phase development
Patient stratification and precision medicine
Imaging as a surrogate marker
Imaging in the real world—challenges to implementation
Summary
References
19. Intellectual property in drug discovery and development
What is a patent?
The patent specification
What can be patented?
Requirements for patentability
Patent issues in drug discovery
The state of the art
Patent documents as state of the art
Evaluation by the patent professional
Sources of information
Results of the evaluation—new chemical entities
Obtaining patent protection for a development compound
Further reading
Useful websites
Patent offices
Professional organizations
Lists of links
20. Regulatory affairs
Introduction
Brief history of pharmaceutical regulation
International harmonization
Roles and responsibilities of health authority, regulatory authority and company
The drug development process
Regulatory procedures
Administrative rules
List of abbreviations
References
Website references
21. The role of pharmaceutical marketing
Introduction
Pharmaceutical marketing—background
Product life cycle
Pharmaceutical product life cycle (fig. 21.2)
Traditional pharmaceutical marketing
Market access
Pricing
Risk and uncertainty
Managed entry agreements
Changing environment—changing marketing
The future of marketing
References
Section 4. Facts and figures
22. Drug discovery and development: The future?
Recent advances in technology
Spending
Sales revenues
Timelines
Pipelines and attrition rates
Biotechnology-derived medicines
Recent introductions
Predicting the future?
References
Index

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