Vioxx以後の医薬品の安全性：欧州/米国における新たな法律、規制、企業戦略

Abstract

The new management report, Drug Safety in the Post-Vioxx Era: New legislation, regulation and company strategies in Europe and the US, examines the actions taken by legislative and regulatory bodies in response to recent drug safety concerns surrounding the COX-2 inhibitors and antidepressants. The report also analyzes the different management, marketing and technological strategies companies are pursuing to ensure the safety of their products, and provides predictions for the future of drug safety regulation in the US and EU.

Table of Contents

Executive Summary 10

• Overview of drug safety issues 10
• Regulation of drug safety in the US and Europe 11
• New legislation and regulation in the US and Europe 12
• Industry initiatives 13
• Pharmaceutical company strategies 14
• Analysis & predictions for the future 15

Chapter 1 Overview of drug safety issues 18 Summary 18 Introduction 19 Drug safety risks 20 Managing drug safety risk 21 Unmanageable risk: drug withdrawals 23 Vioxx 24 Regulatory reforms 25 Impact on drug development 26 Link between US and European regulatory processes 28

Chapter 2 Regulation of drug safety in the US and Europe 32

• Summary 32
• Introduction 33
• US regulations 33
• Evolution of drug safety testing 34
• Pre-launch mechanisms to ensure drug safety 37
  • Drug approval process 38
  • Manufacturing plant inspections 41
• Post-launch mechanisms to ensure drug safety 41
  • MedWatch 41
  • Adverse Event Reporting System 43
  • Controls on drug usage 44
  • Post-marketing studies 47
  • Drug Safety and Risk Management Drugs Advisory Committee 48
  • Manufacturing plant inspections 48
  • Criminal sanctions 49
• European regulations 50
• History of European drug regulation 50
  • The formation of the EMEA and the MRP 52
• Pre-launch mechanisms to ensure drug safety 53
  • The EMEA 53
  • The Mutual Recognition Procedure 54
• Post-launch mechanisms to ensure drug safety 57
  • Warnings 57
  • Recalls 60
  • Inspections 61
• Conclusion 63

Chapter 3 New legislation and regulation in the US and Europe 66

• Summary 66
• Introduction 67
• Factors that raise the stakes for improving drug safety 67
• Rising adverse drug reactions 68
  • US 68
  • Europe 70
• Growing sourcing of drugs through the Internet 72
  • US 72
  • Europe 77
• Rising lawsuits against manufacturers 79
  • US 79
  • Europe 82
• Impact of DTC advertising in the US 83
• New US legislation and regulation 85
• US legislative response (Congress) 85
  • Bills proposed for drug safety 86
• US regulatory response (FDA) 91
  • Institute of Medicine Drug Safety Study 92
  • Drug Safety Oversight Board 93
  • FDA culture 95
  • Speeding drugs to market 95
  • Approval delays for risky applications 96
  • Increased investigation into counterfeiting 98
  • Heightened scrutiny of DTC advertising 99
  • Budget issues 101
• Other regulators 102
  • New York State Attorney General Eliot Spitzer vs. GSK and Paxil 102
  • State legislative initiatives 105
• New European legislation and regulation 106
• EU level legislation 106
  • Pediatric drug testing 106
  • Production of Active Pharmaceutical Ingredients 107
  • Labeling 108
• Country level legislation 109
• EU level regulation (EMEA) 110
  • EudraVigilance 110
  • Restrictions on use of COX-2 inhibitors 111
  • Restructuring to eliminate conflicts of interest 112
• Country level regulation (Competent Authorities) 112
  • Expanded collection and publication of drug safety data 112
  • Restructuring 113
  • Tightening of controls on consumer drug advertising 114
  • Delayed drug approvals 115
• Conclusion 115

Chapter 4 Industry initiatives 118

• Summary 118
• Introduction 119
• Trade group initiatives 120
  • Pharmaceutical Research and Manufacturers of America (PhRMA) 120
• Consumer group initiatives 122
• Public Citizen 122
• Consumers Union 124
• Institute for Safe Medication Practices 124
• Europe and international industry initiatives 125
• Trade group initiatives 125
  • Association of the British Pharmaceutical Industry 125
• World Health Organization 126
• Managed care companies 127
• Restrictions on usage of unsafe drugs 129
• Drug safety databases 130
• Leveraging data to shape public health care policy 130
  • Medco Institute at UMDNJ for Drug Safety, Policy and
  • Epidemiology 130
• Retailers 131
• Discontinuing of secondary market purchasing by CVS 131
• Conclusion 132

Chapter 5 Pharmaceutical company

• strategies 134
• Summary 134
• Introduction 135
• Marketing and business strategies 136
• Reductions in use of wholesalers 136
  • Pfizers European supply chain reorganization 137
• Adjustments to advertising campaigns 138
• Management strategies 141
• Executive changes 141
  • Replacement of Mercks CEO 141
  • Reorganization of drug development group at AstraZeneca 142
  • Resignation of Able Labs CEO and manufacturing reorganization 143
• Strengthening of government affairs capabilities 144
• Technology programs 146
• Using genomics to predict toxicity 146
• Expanding use of technology to track drug shipments 147
  • Bar-coding 147
  • Radio frequency identification (RFID) 148
• Labeling enhancements 150
• Regulatory responses 151
• Providing more drug data 151
  • GSK 152
  • Forest Laboratories 152
  • AstraZeneca 153
  • Eli Lilly 154
  • Merck 154
• Withdrawals of drug applications 154
• Conclusion 155

Chapter 6 Analysis & predictions for the future 158

• Summary 158
• Introduction 159
• Rising imperatives for drug safety 159
• Rising numbers of adverse reactions 159
• More lawsuits with higher payouts 160
• Wait-and-see stance from congress 161
• FDA overhaul 162
• No meaningful impact from other regulators 163
• Continuing trade group proactivity 163
• Europe trails US in reform 164
• Inconsistent approach to safety by Competent Authorities 164
• EMEA Looks to FDA 165
• Pharmas lead the charge 165
• Rising initiatives address drug counterfeiting 165
• Adjustment of DTC campaigns 166
• Increasing action against errant executives 166
• Greater provision of drug data 167
• Higher clinical trial standards 167
• Increasing involvement from managed care and retail companies 168

Chapter 7 Appendix 172

• Primary research methodology 172
• Glossary 173
• Index 174

List of Figures

• Figure 1.1: The drug safety risk spectrum 22
• Figure 1.2: Average approval time for New Chemical Entities, 1993-2003 26
• Figure 1.3: Impact of drug development pressures on drug safety 28
• Figure 2.4: Sources of FDA-reported adverse events 44
• Figure 2.5: New applications finalized by RMS, 2004 56
• Figure 2.6: Number of public drug safety warnings by country, 2002-2005* 59
• Figure 2.7: Human drugs sampled and tested by EMEA 62
• Figure 3.8: Growth in reported adverse drug events in the US, 1995-2004 68
• Figure 3.9: Consumer responses to rising drug safety risks 70
• Figure 3.10: EU and non-EU adverse drug reaction reports, 2002-2004 71
• Figure 3.11: Drivers of drug re-importation 73
• Figure 3.12: Overall susceptibility of top 5 European drug markets to counterfeiting 77
• Figure 3.13: DTC ad spending ($bn), 2001-2004 84
• Figure 3.14: NDAs and NMAs approved by the FDA, 1997-2004 97
• Figure 3.15: Number of new counterfeit drug cases opened by the FDA, 1997-2004 98
• Figure 3.16: Warning letters sent to drug marketers since expansion of DTC advertising rules, 1997-2003 99
• Figure 3.17: FDA budget, 2001-2006 102
• Figure 5.18: Pressures on drug developers 136
• Figure 5.19: Marketing & advertising expenses, Q4 2004 & Q1 2005 140

List of Tables

• Table 1.1: Potential safety risks of popular drug classes 23
• Table 1.2: Recent drug recalls and affected patients, 1997-2005 24
• Table 2.3: Timeline of key FDA legislation 34
• Table 2.4: CDER advisory committees 37
• Table 2.5: Drugs subject to FDA controls 45
• Table 2.6: Leading national Competent Authorities 57
• Table 2.7: EMEA human drug recalls, 2000-2005 60
• Table 3.8: Pending US legislation 87