John Griffin BSc, PhD, MBBS, FRCP, FRCPath, FFPM; Director, Asklepieion Consultancy Ltd; Visiting Professor, University of Surrey Postgraduate Medical School; Former Director, ABPI; Formerly Professional Head of the Medicines Division, DHSS, London.

John Posner BSc PhD MBBS FRCP FFPM; Independent Consultant in Pharmaceutical Medicine, John Posner Consulting, Beckenham, Kent, UK; Chairman of the Board of Examiners of the Faculty of Pharmaceutical Medicine of the Royal College of Physicians (UK).

Geoffrey R. Barker TD, BSc, MSc, FDSRCD, FRCS, FFPM; Adj. Professor Immunology, Duke University Medical Center, NC, USA; Executive and Limited Partner, Pappas Ventures, NC, USA; Consultant to EGeen (USA), Abingworth LLP (UK), Reuters; Insight Community of Experts; Trustee Member of the Board of the Faculty of Pharmaceutical Physicians of The Royal Colleges of Physicians UK.

Contributors vii

The editors x

Acknowledgements xiii

List of abbreviations xiv

Preface xix

Part I Research and development 1

1 Discovery of new medicines 3
Yves J. Ribeill

2 Pharmaceutical development 32
Michael Gamlen and Paul Cummings

3 Preclinical safety testing 42
Lutz Müller and Elisabeth Husar

4 Exploratory development 82
John Posner

5 Clinical pharmacokinetics 113
Paul Rolan and Valéria Molnár

6 Biological therapeutics 132
Peter Lloyd and Jennifer Sims

7 Objectives and design of clinical trials 143
John Posner and Steve Warrington

8 Conduct of clinical trials: Good Clinical Practice 155
Kate L.R. Darwin

9 Medical statistics 189
Andrew P. Grieve

10 Development of medicines: full development 219
Peter D. Stonier

11 Pharmacovigilance 235
Stephen F. Hobbiger, Bina Patel and Elizabeth Swain

12 Vaccines 254
John Beadle

13 Drugs for cancer 270
James Spicer and Johann De Bono

14 Ethics of human experimentation 286
Jane Barrett

15 Drug development in paediatrics and neonatology 295
Nazakat M. Merchant and Denis V. Azzopardi

16 Due diligence and the role of the pharmaceutical physician 306
Geoffrey R. Barker

Part II Regulation 317

17 A history of drug regulation in the UK 319
John P. Griffin

18 The Clinical Trials Directive 347
Fergus Sweeney and Agnès Saint Raymond

19 Human medicinal products in the European Union: Regulations Directives and structures 360
Agnès Saint Raymond and Anthony J. Humphreys

20 Human medicinal products in the European Union: Procedures 379
Agnès Saint Raymond and Anthony J. Humphreys

[...]opean regulation of medical devices 418
Shuna Mason

22 Paediatric regulation 435
Heike Rabe and Agnès Saint-Raymond

23 Technical requirements for registration of pharmaceuticals for human use: The ICH process 447
Dean W.G. Harron

24 The regulation of drug products by the US Food and Drug Administration 461
Peter Barton Hutt

25 The US FDA in the drug development evaluation and approval process 501
Richard N. Spivey, Judith K. Jones, William Wardell and William W. Vodra

26 Future prospects of the pharmaceutical industry and its regulation in the USA 518
Richard N. Spivey, William W. Vodra, Judith K. Jones and William Wardell

27 Regulatory and clinical trial systems in Japan 537
Mamiko Satake and Natsuko Hosoda

28 The regulation of therapeutic products in Australia 554
Elizabeth de Somer, Deborah Monk and Janice Hirshorn

Part III Health care marketplace 587

29 An Introduction to life cycle management of medicines 589
David Gillen

30 Availability of medicines online and counterfeit medicines 597
Ruth Diazaraque and David Gillen

31 The supply of unlicensed medicines for individual patient use 610
Ian Dodds-Smith and Ewan Townsend

32 Legal and ethical issues relating to medicinal products 632
Nick Beckett, Sarah Hanson and Shuna Mason

33 Medical marketing 653
David B. Galloway and Bensita M.V. Thottakam

34 Information and promotion 670
Charles De Wet

35 Economics of health care 692
Carole A. Bradley and Jane R. Griffin

36 Controls on NHS medicines prescribing and expenditure in the UK (a historical perspective) with some international comparisons 707
John P. Griffin and Geoffrey R. Barker

37 Pharmaceutical medicine in the emerging markets 728
Nadarajah Sreeharan, Jennie A. Sykes and Richard B. Nieman

38 Biosimilars 744
Raymond A. Huml and John Posner

Appendix 1 Declaration of Helsinki 751

Appendix 2 Agreements and Guidelines for Implementation of Clinical Trials 755

Appendix 3 Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 771

Appendix 4 PharmaTrain Syllabus 2010 783

Index 788