EU Paediatric Medicines Regulation: Boon or Burden?

Table of Contents

CHAPTER 1 INTRODUCTION

• 1.1 The Paediatric Medicines Regulation
• 1.2 The need for paediatric testing
• 1.3 The history of the Regulation

CHAPTER 2 THE PAEDIATRIC REGULATION

• 2.1 The text of the Regulation
• 2.2 The Paediatric Committee
  • 2.2.1 Committee composition
  • 2.2.2 Objectives
  • 2.2.3 Safeguards
• 2.3 Marketing authorisation requirements
  • 2.3.1 General authorisation requirements
  • 2.3.2 Waivers
  • 2.3.3 Paediatric investigation plans
  • 2.3.4 Deferrals
  • 2.3.5 Compliance with the PIP
  • 2.3.6 Procedure
  • 2.3.7 Advice
• 2.4 Marketing authorisation procedures
  • 2.4.1 Patented products
  • 2.4.2 Off-patent products
  • 2.4.3 Identification
    • 2.4.3.1 Choice of symbol
• 2.5 Post-authorisation requirements
• 2.6 Rewards and incentives
  • 2.6.1 Patented products
  • 2.6.2 Orphan products
  • 2.6.3 Off-patent products
  • 2.6.4 Additional funding
• 2.7 Communication and co-ordination
  • 2.7.1 Clinical trials register
  • 2.7.2 Paediatric therapeutic needs inventory
  • 2.7.3 European network of expertise
  • 2.7.4 Paediatric study reporting requirements
• 2.8 General and final provisions
  • 2.8.1 Reports and analyses
  • 2.8.2 Annex
• 2.9 Amending Regulation
• 2.10 Deadlines

CHAPTER 3 THE EMEA AND THE PAEDIATRIC COMMITTEE

• 3.1 EMEA funding
• 3.2 EMEA implementation priorities
• 3.3 EMEA paediatric activity 1995-2005
  • 3.3.1 Analysis
  • 3.3.2 Conclusions
• 3.4 Paediatric Expert Group (PEG)
  • 3.4.1 Mandate and objectives
  • . . . Product-related tasks
  • . . . Non-product related activities
  • . . . Activities with external parties
  • 3.4.2 PEG publications
  • 3.4.3 The PEG and the Paediatric Committee
• 3.5 Paediatric Committee

CHAPTER 4 TEDDY

• 4.1 Objectives
• 4.2 Partners
• 4.3 Activities
  • 4.3.1 Ethics
    • 4.3.1.1 Ethics and pharmacogenetics
  • 4.3.2 Pharmacoepidemiology
  • 4.3.3 Genomics and paediatric pharmacogenetics
  • 4.3.4 Methodology of paediatric clinical trials
  • 4.3.5 Key therapeutic questions in children
  • 4.3.6 Rare diseases
  • 4.3.7 Post-marketing studies
  • 4.3.8 Paediatric drug databases
  • 4.3.9 Gender issues in drug evaluation

CHAPTER 5 US AND EU APROACHES

• 5.1 The US paediatric initiatives
• 5.2 Evaluation of the US paediatric initiatives
  • 5.2.1 FDA assessments
    • 5.2.1.1 2001 status report
    • 5.2.1.2 Recent FDA data
  • 5.2.2 Tufts Impact Report
  • 5.2.3 Congressional criticisms
  • 5.2.4 Public Citizen
• 5.3 Lessons from the US experience
• 5.4 What the EU has learned from the US experience

CHAPTER 6 OPPORTUNITIES AND COSTS: RAND AND THE EUROPEAN COMMISSION

• 6.1 R&D-based companies
  • 6.1.1 Costs
  • 6.1.2 Rewards
• 6.2 Generic companies and SMEs
  • 6.2.1 Costs
  • 6.2.2 Incentives
  • 6.2.3 Orphan drugs
  • 6.2.4 Paediatric study programme
• 6.3 The EMEA
• 6.4 Healthcare systems
  • 6.4.1 Costs
  • 6.4.2 Benefits
• 6.5 Children
• 6.6 EU research bodies
• 6.7 Impact outside the EU

CHAPTER 7 OPPORTUNITIES AND COSTS: AN ALTERNATIVE ANALYSIS

• 7.1 Criticisms of the Rand report
• 7.2 An alternative calculation of rewards and costs
• . . . Calculation 1
• . . . Alternative calculation 1
• . . . Calculation 2
• . . . Alternative calculation 2
• . . . Calculation 3
• . . . Alternative calculation 3
• . . . Calculation 4
• . . . Alternative calculation 4
• 7.3 Impact on R&D-based companies
  • 7.3.1 Costs
  • 7.3.2 Rewards
• 7.4 Impact on generic companies
• 7.5 Impact on regulatory agencies
  • 7.5.1 The EMEA
  • 7.5.2 National regulatory authorities
• 7.6 Impact on healthcare systems

CHAPTER 8 WHAT HAPPENS NEXT

• 8.1 Requirements for companies
  • 8.1.1 All companies
  • 8.1.2 Companies seeking SPC extensions
  • 8.1.3 Companies discontinuing a paediatric product
  • 8.1.4 Pharmacovigilance
• 8.2 Approval routes
  • 8.2.1 Centralised approval
  • 8.2.2 Decentralised approval
• 8.3 Penalties for non-compliance
• 8.4 Clinical trials
• 8.5 Databases
  • 8.5.1 EudraPharm
  • 8.5.2 EudraVigilance
  • 8.5.3 EudraCT
• 8.6 Identifying unmet paediatric needs
  • 8.6.1 Paediatric research needs
  • 8.6.2 Paediatric research priorities for off-patent drugs

CHAPTER 9 CONTROVERSIES AND UNCERTAINTIES

• 9.1 SPCs - too much?
  • 9.1.1 Political disagreements
  • 9.1.2 Alternatives
  • 9.1.3 Support for six months
• 9.2 PUMAs and MICE - too little?
  • 9.2.1 Data protection
  • 9.2.2 Formulations and formularies
  • 9.2.3 Paediatric Study Fund
  • 9.2.4 Potential PUMA applicants

CHAPTER 10 CONCLUSION

• 10.1 What the Regulation should achieve
• 10.2 What the Regulation may not achieve
• 10.3 Summary of benefits

APPENDIX A

APPENDIX B

REFERENCES

LIST OF TABLES

• Table 2.1: Deadlines set out in the Paediatric Regulation
• Table 3.1: Table EMEA Paediatric Costs in € millions, 2007-2012
• Table 3.2: Priorities for implementing the Paediatric Regulation in 2006 and 2007
• Table 6.1: Children in EU-27 by Age Groups (millions), 2005-2015
• Table A.1: EMEA priority list of off-patent products

LIST OF FIGURES

• Figure 5.1: New label information for paediatric use by therapeutic area in the US, 1998-2005
• Figure 5.2: Prescription drugs awarded paediatric exclusivity according to total brand sales in 2004 ($mn)
• Figure 5.3: Estimates of paediatric drug study costs over time