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The new 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
 
Drug safety in the post-Vioxx era
 
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
 
iv
 
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
 
v
 
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
 
vi
 
Conclusion 132
 
Chapter 5 Pharmaceutical company
 
strategies 134
 
Summary 134
 
Introduction 135
 
Marketing and business strategies 136
 
Reductions in use of wholesalers 136
 
Pfizer’s European supply chain reorganization 137
 
Adjustments to advertising campaigns 138
 
Management strategies 141
 
Executive changes 141
 
Replacement of Merck’s 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
 
vii
 
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
 
viii
 
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