The Textbook of Pharmaceutical Medicine E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 2729

Veröffentlichungsjahr: 2013

Beschreibung

The Textbook of Pharmaceutical Medicine is the standard reference for everyone working and learning in pharmaceutical medicine. It is a comprehensive resource covering the processes and practices by which medicines are developed, tested and approved, and the recognised text for the Diploma in Pharmaceutical Medicine from the Faculty of Pharmaceutical Medicine.

This fully revised Seventh Edition, which includes two new Editors, encompasses current developments within pharmaceutical medicine with new chapters on biological therapeutics, pharmacovigilance, vaccines, drugs for cancer, drug development in paediatrics and neonatalogy, the clinical trials directive, life cycle management of medicines, counterfeit medicines and medical marketing. Also included for easy reference, and referred to throughout the text, are the Declaration of Helsinki, Guidelines and Documentation for Implementation of Clinical Trials, relevant European Directives and the Syllabus for Pharmaceutical Medicine.

Written by an international team of leading academics, medical directors and lawyers, The Textbook of Pharmaceutical Medicine, Seventh Edition meets the needs of both those working in pharmaceutical medicine and preparing for the Diploma in Pharmaceutical Medicine.

The text breaks down into three core sections:

Part I: Research and Development
Part II: Regulation
Part III: Healthcare marketplace

View Table of Contents in detail

Leseprobe

Table of Contents

Title page

Copyright page

Contributors

The editors

Acknowledgements

List of abbreviations

Preface

Part I: Research and development

1 Discovery of new medicines

Introduction

Medicines marketed in the years 2008–2011

Impact of high throughput screening in drug discovery

Impact of combinatorial chemistry on drug discovery

Fragment-based design

Examples in drug discovery

Oligonucleotide-based therapeutics

Recent drug discovery strategies to improve success

Drug repositioning

The new role of academia in pharmaceuticals

Conclusions

2 Pharmaceutical development

Introduction

Drug delivery

Product formulation types

Quality by Design

Drug substance properties at the preclinical testing stage

Principles of pharmaceutical development

Oral solid dosage form development

Sterile products

Conclusions

3 Preclinical safety testing

Introduction

Preclinical safety pharmacology

Single-dose studies

Repeat-dose studies

Carcinogenicity studies

Reproductive toxicology

Genotoxicity testing

Irritation and sensitisation testing

Specific considerations for biologicals

Animal numbers, costs and ethics

4 Exploratory development

Introduction

Planning exploratory development

Requirements for administration of an NME to humans

Preparation for the first administration to humans

Studies in healthy volunteers

Objectives of first-in-human studies

Design of the first-in-human study

Minimising risk

Subsequent studies in exploratory development

Outcomes of ED

5 Clinical pharmacokinetics

Introduction

Basic concepts

Bioavailability and bioequivalence

Drug interactions

The elderly

Renal impairment

Liver disease

Disposition, rates and routes of elimination of radiolabelled drug

Pharmacokinetic–pharmacodynamic modelling

Population analysis

The rest of the typical clinical pharmacokinetics package

The ideal drug from the point of view of pharmacokinetics

Role of pharmacokinetic properties in determining a dosage regimen

Conclusions

6 Biological therapeutics

Introduction – the history of biologics development

Differences between ‘chemical’ and ‘biological’ molecules

Immunogenicity

First-in-human dose selection for a biologic

Conclusions

7 Objectives and design of clinical trials

History of the controlled clinical trial

Objectives of clinical trials in drug development

Design of controlled clinical trials

Analysis of controlled clinical trials

Final word

8 Conduct of clinical trials: Good Clinical Practice

Introduction

Good Clinical Practice

Preparation of documentation for the clinical trial

The IMP and its documents

Running the clinical trial

Preparation of the clinical report

Quality management

Conclusions

9 Medical statistics

Introduction

Probability

Scales of measurement and clinical endpoints

Basic statistical principles

Issues in design

Meta-analysis and summaries

10 Development of medicines: full development

Introduction

Taking products into later development phase

Preparing the plan

The detailed clinical development plan

Executing the plan

Acknowledgements

11 Pharmacovigilance

Introduction

Legislation and the regulatory authorities

Safety governance

Case handling, expedited and periodic reporting

Signal detection and signal evaluation

Benefit–risk evaluation

Labelling and risk management planning

12 Vaccines

Vaccines: history, controversies and public health issues

Vaccine clinical trials

Vaccine safety monitoring

Vaccinology ethics

Importance of vaccine manufacturing and supply

The future of vaccinology

13 Drugs for cancer

Introduction

Biology of cancer

Rationally designed therapies

Pharmacogenetics, pharmacogenomics and patient selection for treatment

Resistance mechanisms

Cancer drug discovery and preclinical development

Clinical trials in oncology

Current issues in oncology clinical drug development

Conclusions and future perspectives

14 Ethics of human experimentation

Introduction

Principles of ethical biomedical research

History

Informed consent

Children in research

Adults unable to give consent

Who should seek consent?

Research Ethics Committees

Assessment of risk

Conclusions

15 Drug development in paediatrics and neonatology

History and milestones of paediatric drug development

Need for clinical drug studies in paediatrics

Developmental pharmacology – differences between adults, children and neonates and implications for research

Difficulties of performing clinical trials in children

Ethical considerations for paediatric clinical drug trials

Regulatory requirements

Conclusions

16 Due diligence and the role of the pharmaceutical physician

Introduction

Role of the pharmaceutical physician

Scope of due diligence

Process of due diligence

Writing and assembling the due diligence report

Due diligence in private equity and life science transactions

Conclusions

Part II: Regulation

17 A history of drug regulation in the UK

Introduction

The thalidomide disaster and its immediate aftermath

Voluntary controls in the UK (1963–1971)

Voluntary adverse reaction reporting system: Yellow Card scheme

Manufacturers’ licences and Good Manufacturing Practice

Wholesale dealers’ licences

General safety measures

Scrutiny of functioning of the Medicines Division and the establishment of the Medicines Control Agency

Medicines and Healthcare products Regulatory Agency

European dimensions

International dimensions

Conclusions

Update

18 The Clinical Trials Directive

Introduction

History of the Clinical Trials Directive

Scope and content of the clinical trials and GCP Directives

Protection of vulnerable subjects in clinical trials

Clinical trials guidelines

EU databases

Clinical trials and marketing authorisations

Inspections of clinical trials

Clinical Trials Facilitation Group

Revision of the clinical trials legislation

19 Human medicinal products in the European Union: Regulations, Directives and structures

Introduction

Overview of the European Union

European pharmaceutical legislation

European Medicines Agency

International harmonisation

20 Human medicinal products in the European Union: Procedures

Applications for marketing authorisations

Centralised applications

National applications

Application for change in classification of supply

Application for orphan medicine designation

Application for Paediatric Investigation Plan or waiver

Applications for scientific advice and protocol assistance

Application for registration of herbal medicinal products

Applications for clinical trials authorisation

Post-approval variations to marketing authorisations

European Union referrals to CHMP

Product literature, promotion and advertising

Pharmacovigilance

Wholesale distribution, pricing and reimbursement

21 European regulation of medical devices

Introduction

Law on specific devices

Resolution of uncertainties

Competent authorities and notified bodies

What is a medical device?

The drug–device borderline

Drug–device combinations

Classification of devices

Conformity assessment procedures and CE marking

Registration

Harmonised standards

Custom-made devices

Systems and procedure packs

Reprocessing

Essential requirements

Information supplied by the manufacturer

Who is a manufacturer?

Manufacturers outside the EEA

‘Placing on the market’ and ‘putting into service’

Clinical investigation

In vitro diagnostics

Advanced therapy medicinal products

Adverse event reporting: vigilance

General product safety Directive

Recall

Enforcement and sanctions

22 Paediatric regulation

Introduction

Case study

Paediatric population in the European Union

New paediatric medicines Regulation

Aims and objectives of the Regulation

Other tasks of the European Medicines Agency

Ethical aspects of studies in children

Summary and outlook

23 Technical requirements for registration of pharmaceuticals for human use: The ICH process

Introduction

ICH organisation (1990–2003)

The ICH process

ICH 5 Meeting Report

The CTD post-ICH 5

ICH 6: November 2003, Osaka

ICH organisation (2003–2007)

ICH organisation: (2007–2011) and press releases

Revised ICH Terms of Reference [16]

Conclusions to date

24 The regulation of drug products by the US Food and Drug Administration

Introduction

Regulatory framework

FDA history

Historical overview of drug regulation statutes

Other pharmaceutical products

Two classes of drug products

Regulation of non-prescription drugs

Regulation of prescription drugs

Biological drugs

Enforcement

Conclusions

25 The US FDA in the drug development, evaluation and approval process

Introduction

Investigational new drug application

New drug application (NDA or BLA)

Conclusions

26 Future prospects of the pharmaceutical industry and its regulation in the USA

Introduction

Wider aspects of the evolution of the FDA and the pharmaceutical industry from 1962 to 2012

Summary of changing environment and impact on industry

Improvements needed for the future

Conclusions

27 Regulatory and clinical trial systems in Japan

Introduction

Governing law

The Japanese regulatory system

Clinical trial systems

Conclusions

28 The regulation of therapeutic products in Australia

Introduction

History of prescription medicine regulation

TGA registration

Listing on the pharmaceutical benefits scheme – the ‘fourth hurdle’

Access to medicines not registered or listed on the ARTG

Presentation

Patents

Non-prescription medicines and complementary medicines

Medical devices

Part III: Health care marketplace

29 An Introduction to life cycle management of medicines

Introduction

The life cycle management team and the importance of value

Life cycle strategies

Second generation or reformulation of products

Fixed-dose combinations

Indication expansion

Generic investment

Prescription to over-the-counter products

Divestiture

Conclusions

30 Availability of medicines online and counterfeit medicines

Introduction

Definitions of counterfeit, illegally diverted, falsified and substandard drugs

History

Scale of the problem

Three study cases

Actions undertaken to counteract counterfeit drugs

31 The supply of unlicensed medicines for individual patient use

Introduction

EU law

UK law

Particular issues relating to supply of unlicensed medicines

Product liability issues

Professional guidance

Review of the regulatory framework by the MHRA

Conclusions

32 Legal and ethical issues relating to medicinal products

Introduction

Chronology of production, development and marketing

Contractual arrangements in clinical research

Post-authorisation – controls and protection of investment

33 Medical marketing

Introduction

Pharmaceutical market

Strategic planning

Customers

Market research and market intelligence

Promotion

Medical information

Brands

Patients

Franchises

Patent expiry and generics

Demonstrating the benefits of medicine

National Institute for Health and Clinical Excellence

Conclusions

34 Information and promotion

Introduction

Legislation, controls and codes and their enforcement

The Medicines Regulations

Other relevant legislation

Vetting

Monitoring of published advertising material

Handling of complaints

Enforcement

Marketing, advertising and promotion of prescription medicines

Information

Procedural aspects relating to information and promotion

Editorial note

35 Economics of health care

Introduction

Economics of the National Health Service

Measuring the value

Compulsory economic evaluation: the ultimate measure

Conclusions

36 Controls on NHS medicines prescribing and expenditure in the UK (a historical perspective) with some international comparisons

Introduction

NHS and Community Care Act 1990

Problem of the rising NHS medicines bill

Prescription charges for NHS medicines

Pharmaceutical Price Regulation Scheme

Office of Fair Trading report on PPRS and its consequences

2009 Pharmaceutical Price Regulation Scheme

Value-based pricing and the future of PPRS

The Drug Tariff and reference pricing

Contract purchase of medicines from cheap sources

The MacGregor Committee

Generic substitution

Enforced price reductions

Limited or selected lists

Indicative prescribing scheme and GP fundholding

Development of primary care groups

Changing the legal status of medicines from prescription only to over-the-counter availability

Encouragement to prescribe generically

National Institute for Health and Clinical Excellence

European Transparency Directive

Supply of controlled drugs

British National Formulary

International comparisons

Conclusions and future steps within the UK NHS

37 Pharmaceutical medicine in the emerging markets

Introduction

What are ‘emerging markets’?

The pharmaceutical market

Changing patterns of pharmaceutical medicine

Late clinical development

Regulations

Commercialisation of medicines

Development of medicines for the diseases of the developing world

The future: re-engineering R&D through emerging markets

Acknowledgement

38 Biosimilars

Introduction

Biosimilars in Europe

Biosimilars in the USA

Biosimilars in other regions

The future

Appendix 1 Declaration of Helsinki

World Medical Association Declaration of Helsinki

Appendix 2 Agreements and Guidelines for Implementation of Clinical Trials

2.1 Clinical trial agreement for pharmaceutical industry sponsored research in NHS Trusts

1 Definitions

2 Site Principal Investigator

3 Clinical Trial Governance

4 Obligations of the Parties

5 Liabilities and indemnity

6 Confidentiality

7 Publicity

8 Publication

9 Intellectual Property

10 Financial arrangements

11 Term

12 Early termination

13 Relationship between the Parties

14 Agreement and modification

15 Force majeure

16 Notices

17 Rights of Third Parties

18 Waiver

19 Dispute resolution

20 Governing law

2.2 ABPI form of Indemnity for Clinical Studies

2.3 ABPI Guideline on Advertising for Subjects for Clinical Trials

1 Essential Information for an Advertisement

2 Additional Permitted Content

3 Statements That Should Not Be Used

2.4 Guidelines for company-sponsored Safety Assessment of Marketed Medicines (SAMM)

Introduction

Scope of guidelines

1 Definition of Safety Assessment of Marketed Medicines

2 Scope and objectives of SAMM

3 Design of studies

4 Conduct of studies

5 Liaison with regulatory authorities

6 Promotion of medicines

7 Doctor participation

8 Ethical issues

9 Procedure for complaints

10 Review of Guidelines

Appendix 3 Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001

The European Parliament and the Council of the European Union

Have adopted this directive

Appendix 4 PharmaTrain Syllabus 2010

1 Discovery of Medicines

2 Development of Medicines: Planning

3 Non-Clinical Testing

4 Pharmaceutical Development

5 Exploratory Development (Molecule to Proof-of-Concept)

6 Confirmatory Development: Strategies

7 Clinical Trials

8 Ethics and Legal Issues

9 Data Management and Statistics

10 Regulatory Affairs

11 Drug Safety, Pharmacovigilance and Pharmaco-epidemiology

12 Information, Promotion and Education

13 Economics of Health Care

14 Therapeutics

Index

This edition first published 2013, © 2013 by John Wiley & Sons, Ltd; 1993, 1994, 1998 © The Queen’s University Belfast; 2002, 2006, 2009 © Blackwell Publishing Ltd

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Library of Congress Cataloging-in-Publication Data

The textbook of pharmaceutical medicine / edited by John P. Griffin, John Posner, Geoffrey R. Barker. – 7th ed.

p. ; cm.

 Includes bibliographical references and index.

ISBN 978-0-470-65987-8 (cloth : alk. paper)

I. Griffin, J. P. (John Parry) II. Posner, John. III. Barker, Geoffrey R.

[DNLM: 1. Drug Approval. 2. Clinical Trials as Topic. 3. Pharmacology. QV 771]

615.1–dc23

2012037180

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover design by Sarah Dickinson

Contributors

Denis V. Azzopardi, F MedSciProfessor of Neonatal MedicineInstitute of Clinical SciencesImperial College LondonLondon, UK

Geoffrey R. Barker, TD, BSc, MSc, MBBS, FDSRCS, FRCS, FFPMIndependent Consultant in Pharmaceutical MedicineLimited Partner, Pappas Ventures, NC, USA;Board Member, Trustee and Registrar Faculty of Pharmaceutical Medicine of The Royal Colleges of Physicians UKFormer Adj. Professor Immunology, Duke University Medical Center, NC, USAFormerly Chief Medical and Scientific Officer, Quintiles Transnational Corp, NC, USA

Jane Barrett, MBBS, FFPM, LLMThe Barrett ConsultancyGawsworth, Cheshire, UK

John Beadle, MBBCh, MBAChief Executive Officer,PsiOxus Therapeutics LimitedAbingdon, Oxfordshire, UK

Nick Beckett, BSc (Hons)Partner, CMS Cameron McKenna LLPLondon, UK

Carole A. Bradley, MScBoehringer Ingelheim Canada LtdBurlington, ON, Canada

Paul Cummings, BSc(Hons), CBiol, FSB, EurProBiol, FRIDirector of Pharmaceutical DevelopmentPharmaceutical Development Services Ltd Nottingham, UK

Kate L.R. Darwin, BA, DPhil, MRQA, MICR, CSciHammersmith Medicines Research LtdLondon, UK

Johann De Bono, MBChB, MSc, PhD, FRCP, FMedSciProfessor of Experimental Cancer MedicineDrug Development UnitInstitute of Cancer Research;Honorary Consultant Medical OncologistRoyal Marsden NHS Foundation TrustSutton, UK

Elizabeth de Somer, BN, MMedScDirector, Health Policy & ResearchMedicines AustraliaDeakin, ACT, Australia

Charles De Wet, MBChB, MPharMed, FFPM, FIoDMedical DirectorUK and IrelandBoehringer Ingelheim LtdBracknell, UK

Ruth Diazaraque, MD, PhD, MBA, MSc Research Method, MSc Pharm MedSr Director Medical AffairsGilead Sciences LtdUxbridge, UK

Ian Dodds-Smith, MA (Cantab)Partner, Arnold & Porter (UK) LLPLondon, UK

David B. Galloway, MB, ChB, DRCOG, FRCP, FRCPE, FFPMMedical & Scientific DirectorCytosystems LtdAberdeen, Scotland

Michael Gamlen, BSc, PhD, MRPharmS, FRSCManaging DirectorPharmaceutical Development Services LtdNottingham, UK

David Gillen, BSc, MRCGP, FFPMSenior DirectorHead of Medical AffairsCelgene UK and IrelandLondon, UK

Andrew P. Grieve, BSc, MSc, PhD, DScSenior Vice President Clinical Trials MethodologyAptiv Solutions GmbHCologne, Germany

Jane R. Griffin, BA(Hons), MScDirector, Market Access, Pricing and Outcomes ResearchBoehringer Ingelheim LtdBracknell, Berkshire, UK

John P. Griffin, BSc, PhD, MBBS, FRCP, FRCPath, FFPMDirector, Asklepieion Consultancy Ltd;Visiting Professor, University of Surrey Postgraduate Medical School;Former Director, ABPI;Formerly Professional Head of the Medicines Division, DOH (now MHRA), London, UK

Sarah Hanson, MAPartner, CMS Cameron McKenna LLPLondon, UK

Dean W.G. Harron, PhD, FRPharmS, MPSNISchool of PharmacyQueens UniversityBelfast, Northern Ireland

Judith Hirshorn, BSc (Hons), PhD, FAICDConsultantRose BayNSW, Australia

Stephen F. Hobbiger, BSc, FRCP(E), FFPMVice President and European Qualified Person for PharmacovigilanceGlaxoSmithKline R&DStockley ParkUxbridge, UK

Natsuko HosodaMedical & Regulatory AffairsQuintiles Transnational Japan KKTokyo, Japan

Raymond A. Huml, MS, DVM, RACQuintilesDurham, NC, USA

Anthony J. Humphreys, BSc (Pharm), MSc (Pharmaceutics), MPSIHead of Regulatory, Procedural and Committee SupportPatient Health ProtectionEuropean Medicines AgencyLondon, UK

Elisabeth Husar, DVM, MAS (Toxicology)Head Toxicology Project LeadsF. Hoffmann-La Roche LtdBasel, Switzerland

Peter Barton Hutt, LLB, LLMSenior Counsel, Covington & Burling;Lecturer on Food and Drug Law, Harvard Law School;Former Chief Counsel, US Food and Drug AdministrationWashington, DC, USA

Judith K. Jones, MD, PhD, FISPEPresident, The Degge Group, Ltd.President, The Pharmaceutical Education & Research Institute, Inc.& Adjunct Professor of Pharmacology, Georgetown University School of Medicineand University of Michigan School of Public HealthArlington, VA, USA

Peter Lloyd, BSc, PhDExecutive Director; Head PKPD Biologics Safety and Disposition, NovartisNovartis Institutes for Biomedical ResearchHorsham, UK

Shuna Mason, BA (Hons)Solicitor, Head of RegulatoryCMS Cameron McKenna LLPLondon, UK

Nazakat M. Merchant, MBBS, CFM, DCH, MRCPCHAcademic Clinical Lecturer, NeonatologyCentre for the Developing BrainPerinatal Imaging and HealthKing’s CollegeSt Thomas’ HospitalLondon, UK

Valéria Molnár, MScPharmDirectorClinical Pharmacology Consulting LtdBeaumont, Australia

Deborah Monk, BPharm, Dep Hosp BAInnovation and Industry PolicyMedicines AustraliaDeakin, ACT, Australia

Lutz Müller, PhDLead Late Stage Projects ToxicologyF. Hoffmann-La Roche LtdBasel, Switzerland

Richard B. Nieman, MB BS, FRCPVice President and Head of Medical Affairs, AsiaBayer Healthcare PharmaceuticalsBeijing, China

Bina Patel, BSc (Hons)Director, International Safety Affiliates (EEMEA)AmgenUxbridge, UK

John Posner, BSc, PhD, MBBS, FRCP, FFPMIndependent Consultant in Pharmaceutical MedicineJohn Posner ConsultingBeckenham, Kent, UK;Visiting Professor, School of Biomedical Sciences, King’s College London, UK

Heike Rabe, MD, PhD, FRCPCHSenior Clinical LecturerBrighton and Sussex Medical School;Honarary Consultant NeonatologistBrighton and Sussex University Hospitals NHS TrustBrighton, UK

Yves J. Ribeill, PhD, CChem, MRSCPresident and CEOSCYNEXIS, Inc.Research Triangle Park, NC, USA

Paul Rolan, MB, BS, MD, FRACP, FFPM, DCPSAProfessor of Clinical and Experimental PharmacologyMedical SchoolUniversity of AdelaideAdelaide, Australia

Agnès Saint Raymond, MDHead of Human Medicines Special AreasMember of the UN Commission on Life-Saving Commodities for Women and ChildrenHuman Medicines Development and EvaluationEuropean Medicines AgencyLondon, UK

Mamiko SatakeCorporate DevelopmentQuintiles Transnational Japan KKTokyo, Japan

Jennifer Sims, BSc, PhDIntegrated Biologix GmbHBasel, Switzerland

James Spicer, MA, FRCP, PhDReader in Experimental Oncology and Consultant in Medical OncologyCancer Early Phase Trials UnitKing’s Health Partners at Guy’s HospitalLondon, UK

Richard N. Spivey, PharmD, PhDSenior Vice PresidentGlobal Regulatory AffairsAllerganIrvine, CA, USA

Nadarajah Sreeharan, MD, PhD, FRCP, FACP, FFPMSenior Partner, Transcrip-Partners LLPVisiting Professor, King’s College London, London, UKSenior Visiting Professor, UITM Medical School, Malaysia

Peter D. Stonier, MBChB, BSc, PhD, FRCP, FFPMVisiting Professor of Pharmaceutical MedicineSchool of Biomedical SciencesKing’s College LondonLondon, UK

Elizabeth Swain, MRPharm.SDirector Pharmacovigilance Advocacy and PolicyGlaxoSmithKline R&DStevenage, UK

Fergus Sweeney, PhDHead of Compliance and InspectionPatient Health ProtectionEuropean Medicines AgencyLondon, UK

Jennie A. Sykes, MBChB, MRCP, FFPMVice President, Global Medical Centre of ExcellenceHead, GSK Academy of Pharmaceutical MedicineGlaxoSmithKlineLondon, UK

Bensita M.V. Thottakam, B Pharm, M Pharm, MscClinical Research ScientistDepartment of Research and DevelopmentCytosystems LtdAberdeen, Scotland

Ewan Townsend, MA (Cantab)Arnold & Porter (UK) LLPLondon, UK

William W. Vodra, JDSenior Partner (Retired), Arnold & Porter LLPWashington, DC, USA

William Wardell, MA (Oxon), MD, PhDPresident, Wardell Associates InternationalPonte Vedra, FL, USA

Steve Warrington, MA, MD, FRCP, FFPMConsultant, Hammersmith Medicines Research LtdLondon, UK

The Editors

Professor John P. Griffin, BSc, PhD, MBBS, FRCP, FRCPath, FFPM graduated in medicine at the Royal London Hospital, where he was also in clinical practice. He was a lecturer in Physiology at King’s College, London and held the post of Head of Clinical Research at Riker Laboratories from 1967 to 1971. Professor Griffin joined the then Medicines Division of the Department of Health, now Medicines Healthcare Agency (MHRA) London, as a Senior Medical Officer, in 1971, and was subsequently appointed Medical Assessor to the Committee on Safety of Medicines. From 1977 to 1984, Professor Griffin was Senior Principal Medical Officer and Professional Head of Medicines Division in addition to being Medical Assessor to the Medicines Commission. As the Professional Head of Medicines Division he also attended the Scientific Sub-Committee of the Veterinary Products Committee of the Ministry of Agriculture, Food and Fisheries. During this time he was a member of the EC committee on Proprietary Medicinal Products and Chairman of the CPMP’s Working Party on Safety Requirements.

From 1976 to 1984 John P. Griffin served on the Joint Formulary Committee of the British National Formulary, during which period the first eight issues of the current format were produced.

John P. Griffin was the director of the Association of the British Pharmaceutical Industry from 1984 to 1994. During this time he was a member of the Executive Board of the European Federation of the Pharmaceutical Industries’ Associations and IFPMA. He chaired the ICH Safety Working Group from 1988 to 1994 and presented papers at ICH1 and ICH2 in the plenary sessions.

In 1992 he was invited to deliver the Thomas Young Lecture and was awarded the Thomas Young Gold Medal at St George’s Hospital Medical School, University of London.

Since June 1994, John P. Griffin has run his own independent consultancy company, which has provided independent and impartial advice to governments on the development of a pharmaceutical policy, and to national trade associations and individual companies. John P. Griffin was Visiting Professor in Pharmaceutical Medicine at the University of Surrey for 6 years and was also Honorary Consultant Clinical Pharmacologist at the Lister Hospital in Hertfordshire, UK.

Professor Griffin was on the Board of the Faculty of Pharmaceutical Medicine for 12 years, was Chairman of the Board of Examiners of the Faculty of Pharmaceutical Medicine of the Royal College of Physicians for 7 years, and was Academic Registrar and served on the Task Force on Specialist Medical Training in Pharmaceutical Medicine. He has served on a number of Royal College of Physicians, London Working Parties including that on the ‘Development of Clinical Pharmacology and Therapeutics in a Changing World’.

Professor Griffin is the author and co-author of over 250 publications on adverse drug reactions and iatrogenic disease, aspects of neurophysiology and clinical pharmacology and toxicology and drug regulation. Notable among his publications are the following four standard texts:

Iatrogenic Diseases

. Oxford University Press, 1st edn 1972, 3rd edn 1986; jointly with Professor P.F. D’Arcy.

A Manual of Adverse Drug Interactions

. John Wright, Bristol, 1st edn 1975; Elsevier Press, Amsterdam, 5th edn. 1997; jointly with Professor P.F. D’Arcy.

The Textbook of Pharmaceutical Medicine

. The Queen’s University of Belfast Press, 1st edn 1993, 2nd edn 1994, 3rd edn 1998, 4th edn 2002 published by the BMJ Publishing Group in 2002, 5th edn 2006 and 6th edn 2009, Blackwell.

Medicines, Research, Regulation and Risk

. The Queen’s University of Belfast Press, 1st edn 1989, 2nd edn 1992.

From 1991 to 2003 he served as Editor in Chief of Adverse Drug Reactions and Toxicological Reviews, a peer-reviewed journal produced quarterly by Oxford University Press.

In 2005 he was awarded the Faculty of Pharmaceutical Medicines Commemorative Medal for outstanding services to the Faculty.

Professor John Posner, BSc PhD MBBS FRCP FFPM gained a BSc and PhD in pharmacology at King’s College London and qualified in medicine at King’s College Hospital in 1974. After holding various medical posts in London, he completed a residency in Internal Medicine at the Soroka Medical Centre in Beer Sheva, Israel. He subsequently worked as an Attending Physician at Soroka and Lecturer at Ben Gurion University of the Negev.

With the desire to spend more time in clinical drug research, John returned to the UK in 1982, joining the Wellcome Research Laboratories. He developed and validated models of analgesia in healthy volunteers and applied these to the evaluation of novel, peripherally acting opioids. He also used a variety of pharmacodynamic tests in the evaluation of drugs for epilepsy, stroke and migraine. Other areas of in­­vestigation included drugs for allergy, asthma depression and anti-infectives. Studies in patients included investigation of a novel agent for sickle cell disease and one of the first biologics for lymphoma.

In 1986, John was appointed Head of Clinical Pharmacology at Wellcome, becoming responsible for the evaluation of all new molecular entities emanating from Wellcome’s discovery research in the UK. He negotiated the design and build of a new clinical research facility at King’s College Hospital Medical School, where his department subsequently conducted their phase I studies. He continued to practise medicine and teach students on a part-time basis as Honorary Senior Lecturer in Medicine at King’s. With the acquisition of Wellcome by Glaxo in 1995, John was appointed an International Director of Clinical Pharmacology at GlaxoWellcome.

After a period with a consultancy and contract research organisation, John started working as an independent consultant in 1999. He continues to work in a wide range of therapeutic areas, assisting companies with their strategic planning, design, conduct and reporting of exploratory studies of novel compounds from ‘first-in-human’ to ‘proof of concept’. His work also includes preparation of clinical overviews, summaries and briefing documents for regulatory submissions worldwide, serving on data monitoring and governance committees and advising on licensing opportunities.

John has extensive postgraduate teaching commitments, organising and participating in courses for physicians and scientists in pharmaceutical companies and academia. He has been a long-standing, active member of the Board of Examiners of the Faculty of Pharmaceutical Medicine of the Royal College of Physicians and served as its Chair for a period of 3 years. John established a Diploma and Certificate in Human Pharmacology for the Faculty; the Diploma is now a recognised qualification for Principal Investigators. He continues to serve as Director of these programmes and has responsibility for a number of MSc modules at King’s College, London, where he is a Visiting Professor in the School of Biomedical Sciences. John has published extensively and is an Executive Editor of the British Journal of Clinical Pharmacology.

Professor Geoffrey R. Barker, TD, BSc, MSc, FDSRCS, FRCS, FFPM graduated from Guy’s Hospital Dental and Medical Schools with a 1st class honours degree in physiology, a distinction and honours in dental surgery and MBBS medicine in 1973. He held assistant lecturer posts in Dental anatomy, Physiology and Restorative Dentistry at Guy’s Hospital Medical and Dental Schools and subsequently completed his training to become a Principal in Medical Practice. Over the next several years Professor Barker continued to pursue his interests in clinical research, medical and surgical practice and gained a Masters in Medicine from Manchester University and Fellowships in London (FDSRCS) and Edinburgh (FRCS).

In 1987 he was awarded the Chair in Oral Surgery Medicine and Pathology for the University of Wales. In this role Professor Barker specialised in major reconstructive surgery, cleft lip and palate surgery, and the clinical development of osseo-integration for the replacement of lost bone with titanium implants. By application of oral pathology he also advanced the understanding of oral manifestations of underlying systemic diseases and their management.

In 1990, his continued interest in the translation of new treatment concepts from the laboratory bench into clinical practice resulted in the opportunity to join the pharmaceutical industry while continuing to hold a position as a consultant surgeon. As Medical Director for Astra Pharmaceuticals UK, Professor Barker played a key part in the development of acid proton pump inhibitors to treat and prevent gastroesophageal reflux disease and peptic ulceration and was able to advance the use of once-daily inhaled steroids for respiratory disease and new management regimens for cardiovascular disease.

In 1997 Professor Barker joined the Medicines Control Agency working with product licensing. In 1999 he was appointed Global Head of Medical Affairs at Actelion Pharmaceuticals and, as a member of the senior management team, successfully steered the company through its IPO and the launch and marketing of its new treatment for pulmonary hypertension.

In 2001 Professor Barker moved to North Carolina to serve as Chief Medical and Scientific Officer for Quintiles Translational Corp, overseeing worldwide clinical trials and the continued development of new medicines. In 2004 he was appointed Adjunct Professor in Immunology at Duke University Medical Center, North Carolina. On retiring from Quintiles, Professor Barker joined Pappas Ventures, a leading health care venture capital fund investing in the development of new medicines and he continues to consult for several venture capital and pharmaceutical companies

Professor Barker became a Member of the Faculty of Pharmaceutical Medicine in 1995 and Fellow in 1998 and was elected Registrar and a Member and Trustee of the Board of the Faculty in 2009.

Acknowledgements

This is the 7th edition of The Textbook of Pharmaceutical Medicine in the 20 years since its first publication. The size of the book has progressively increased and, with it, the breadth of expertise of its contributors. For example, there were 22 contributors to the 1st edition; 44 to the 6th edition and 54 to the current edition. The increase in expertise that this represents has changed the Textbook from being a good book targeted at pharmaceutical physicians to a one-stop shop and the outstanding information source in this field of medicine.

The success of a book depends on the quality of contributors and the editors would like to thank all of them for their delivery of high quality manuscripts. In particular we wish to acknowledge the diligence of those contributors who have contributed to all seven editions.

We would also like to thank those who have generously given permission to reproduce figures and documents; this is acknowledged in the appropriate places in the Textbook.

It is fitting to pay tribute to Professor John O’Grady, co-editor of the first five editions of the Textbook, who died in 2011. His expertise will be missed greatly.

It is fitting to thank our publishers, Wiley-Blackwell, for their exceptional continuing support over many years, particularly Adam Gilbert, Elisabeth Dodds and Rebecca Huxley, whose patience, courtesy and expertise have been outstanding. We are grateful to Aileen Castell for the invaluable help she provided during the production stage of this edition. We would like to thank Jan East for her exemplary copyediting skills on this and the 6th edition. We also wish to thank Mary Banks, who retired in September 2011 but was a pillar of strength in preparing previous editions and in the early stages of the current edition.

Finally, thanks are due to the World Medical Association (WMA) and the European Medicines Agency (EMA) for permission to publish key documents as Appendices. Others have allowed us to quote or use their material and this generosity is acknowledged in the text; however, a general thanks is appropriate at this point.

List of Abbreviations

ABPI

Association of the British Pharmaceutical Industry

ACE

angiotensin converting enzyme

AChE

acetylcholinesterase

ACPM

Advisory Committee on Prescription Medicines

AD

Alzheimer’s disease

ADA

antidrug antibody

ADEC

Australian Drug Evaluation Committee

ADME

absorption, distribution, metabolism and elimination

ADMET

absorption, distribution, metabolism, excretion and toxicological properties

ADR

adverse drug reaction

AEFI

adverse event following immunisation

AF

atrial fibrillation

AFR

annual financial return

AHEC

Australian Health Ethics Committee

AHMAC

Australian Health Ministers’ Advisory Council

AIMD

active implantable medical device

AMWG

Access to Medicines Working Group

ANCOVA

analysis of covariance

ANDA

abbreviated New Drug Application

ANVISA

Brazil’s National Health Surveillance Agency