TONY ELLERY is a consultant with Ellery Pharma Consulting. Until September 2008, he was the Head of Pharmaceutical Lifecycle Management in Portfolio Management at Novartis AG. Prior to this, he occupied positions of increasing seniority in research, development, and marketing at different companies, including Roche, Ciba Vision, and Novartis. Dr. Ellery has served as a member of the Ciba-Geigy Research Advisory Board and the Novartis Pharma Development Management Board. He is a popular speaker on lifecycle, project, and portfolio management.

NEAL HANSEN is the Managing Director of Healthcare Consulting within the Informa Group, encompassing Datamonitor Healthcare Consulting and Phasic Strategy. Previously, he was the European Head of Consulting within Wood Mackenzie's Life Sciences Practice. He works with many key players in the pharmaceutical industry to support effective decision making for brand and portfolio strategy and has chaired and spoken at numerous conferences in the field of lifecycle management and the changing nature of the generic drug industry.

Acknowledgments xvii

Introduction xix

Part A Lifecycle Management Business Environment 1

1. Challenges Facing the Branded Drug Industry 3

1.1 Depleted NME Pipelines/Lower R&D Efficiency 4

1.2 Higher Development Costs 8

1.3 Safety Concerns 9

1.4 Tougher Environment for Pricing, Reimbursement, and Listing 12

1.5 Increased Competition 16

1.6 Earlier Genericization 17

1.7 Faster Sales Erosion Following Patent Expiry 18

1.8 Poor Image of Branded Drug Industry 20

1.8.1 Prosperity of the Branded Drug Industry 21

1.8.2 Lack of Innovation 22

1.8.3 Marketing Spend and Tactics 22

1.8.4 Safety Issues 23

1.8.5 Keeping Generics Off the Market 24

1.9 Diversification 26

2. The Life Cycle of Industries, Technologies, and Brands 30

2.1 Diffusion of Innovations 30

2.2 The Lifecycle Curve 32

2.3 Lifecycle Phases 34

2.3.1 Development Phase 34

2.3.2 Introduction Phase 35

2.3.3 Growth Phase 35

2.3.4 Maturity Phase 36

2.3.5 Decline Phase 36

3. The Life Cycle of a Pharmaceutical Brand 38

3.1 Lifecycle Curve of Pharmaceuticals 41

3.1.1 Slow Rate of Growth during the Growth Phase 42

3.1.2 Lack of a True Maturity Phase 43

3.1.3 Precipitous Decline Phase 43

3.2 Factors Affecting Rate of Conversion to Generics 44

3.2.1 Government Policy 44

3.2.2 Disease 44

3.2.3 Size of Brand 45

3.2.4 Hospital versus Nonhospital Drug Usage 45

3.2.5 Active Substance and Other Barriers to Entry 46

3.3 The Life Cycle of a Pharmaceutical Brand 46

Part B Lifecycle Management Regulatory and Legal Environment 55

4. The Generic Approval Process 57

4.1 United States 57

[...]ope 59

4.3 Japan 61

5. Hatch-Waxman Legislation and Its Effects on LCM 62

5.1 Hatch-Waxman Act of 1984 62

5.2 Medicare Modernization Act of 2003 64

5.3 FDA Amendments Act of 2007 65

5.4 Q1 Program Supplemental Funding Act of 2008 66

5.5 Discussion of Hatch-Waxman Legislation 66

6. U.S. Health-Care Reform 2010 69

[...]opean Sector Inquiry 72

Part C Patents and Exclusivities 77

8. Patents and Other Intellectual Property Rights 79

8.1 Nonpatent Intellectual Property Rights 79

8.2 What Are Patents? 81

8.3 What Is Patentable? 83

8.3.1 Patentable Subject Matter 83

8.3.2 Novelty 84

8.3.3 Inventive Step 85

8.3.4 Utility 86

8.3.5 Disclosure 86

8.4 How Long Does a Patent Last? 87

8.5 Patent Term Restoration in the United States 87

8.6 Supplementary Protection Certificates in Europe 88

8.7 Patent Term Extension in Japan 89

8.8 How Are Patents Obtained? 89

8.9 Patent Enforcement 91

8.10 Types of Patents 92

8.10.1 Composition of Matter Patent 93

8.10.2 Medical Use Patent 93

8.10.3 Formulation Patent 94

8.11 KSR versus Teleflex-Raising the Nonobviousness Bar 94

8.12 Patent Strategy 96

9. Nonpatent Exclusivities 99

9.1 NCE Exclusivity (United States) 99

9.2 New Clinical Study Exclusivity (United States) 100

9.3 Data and Marketing Exclusivity (Europe) 100

9.4 Data Exclusivity (Japan) 101

9.5 Orphan Drug Exclusivity 101

9.6 Pediatric Exclusivity 103

9.7 180-Day Generic Product Exclusivity 105

10. Patent Settlements 107

Part D Developmental LCM 113

11. Strategic Principles of Developmental LCM 115

11.1 Developmental LCM Goal 1: Provide a Meaningful Improvement in Clinical Profile 116

11.2 Developmental LCM Goal 2: Increase the Potential Real-World Patient Potential for the Brand 118

11.3 Developmental LCM Goal 3: The Ability to Generate an ROI 120

11.4 Developmental LCM Goal 4: The Ability to Enhance Market Exclusivity of the Brand Franchise 121

12. Indication Expansion and Sequencing 123

12.1 Categories of Indication Expansion 123

13. Patient Subpopulations and Personalized Medicine 131

13.1 What Does a Good Patient Selection Strategy Look Like? 135

13.2 Patient Selection without Predictive Criteria: Post Hoc Approaches 138

13.3 What about the Patients Who Are Not Selected? 139

14. New Dosage Strengths, New Dosage Regimens 140

14.1 New Dosage Strengths 140

14.2 New Dosage Regimens 141

15. Reformulation, New Routes of Administration, and Drug Delivery 143

15.1 Reformulation and New Routes of Administration 143

15.1.1 Switch and Grow Strategy 143

15.1.2 Expand and Grow Strategy 145

15.1.3 Generic Defense 145

15.2 Drug Delivery Devices 149

16. Fixed-Dose Combinations (FDCs) and Co-Packaging 152

17. Second-Generation Products and Modified Chemistry 159

17.1 Isomerism 160

17.2 Polymorphism 161

17.3 Salts, Ethers, and Esters 162

17.4 Prodrugs and Metabolites 163

18. Other Developmental LCM Strategies 165

18.1 Manufacturing Strategies 165

18.2 White Papers and Citizen Petitions 166

Part E Commercial LCM 167

19. Strategic Principles of Commercial LCM 169

19.1 Commercial LCM Goal 1: The Ability to Drive Widespread and Preferential Patient Access to the Brand 170

19.2 Commercial LCM Goal 2: The Ability to Defend Market Access and Formulary Position 170

19.3 Commercial LCM Goal 3: The Ability to Optimize Profi tability of the Brand Franchise 171

20. Geographical Expansion and Optimization 172

20.1 Geographic Expansion 174

20.2 Harmonization and Rationalization 175

21. OTC Switching 178

21.1 What to Switch: Choosing the Best Approach 179

21.2 Where to Switch: Dealing with Intermarket Variability 181

21.3 When to Switch: Balancing the Product Life Cycle? 183

21.4 How to Make the Switch Successful: What Corporate Support Is Required? 184

22. Brand Loyalty and Service Programs 186

23. Strategic Pricing Strategies 190

23.1 Pricing Strategy and Tactics in the Launch and Growth Phases 190

23.2 Pricing Strategy and Tactics Following Patent Expiry 193

24. Generic Strategies and Tactics 198

Building a Generic Portfolio: Old versus New Thinking 202

25. Exit Strategies 204

Executing the Exit Strategy 206

Part F Biologics and Biosimilars 207

26. Biologics and LCM 209

26.1 Emergence of Biotech 209

26.2 Some Definitions 210

26.2.1 Biologics 210

26.3 Uptake and Value of Biologics 211

26.4 LCM of Biologics 213

26.4.1 Next-Generation Biologics 213

26.4.2 Reformulation 214

26.4.3 Indication Expansion 215

26.4.4 Self-Injection Devices 215

27. Biosimilars and Their Impact on Biologic LCM 217

27.1 Changing Terminology: Biogenerics, Biosimilars, and FOBs 217

27.2 Why Are Biosimilars a Big Deal? 219

27.3 How Are Biosimilars Different? 220

27.4 Biosimilar Approval Pathways 220

27.4.1 Biosimilars in Europe 220

27.4.2 Biosimilars in the United States 221

27.4.3 Biosimilars around the World 222

27.5 Substitution of Biosimilars 223

27.5.1 Automatic Substitution 223

27.5.2 Therapeutic Substitution 224

27.6 Innovator Responses to Biosimilar Threats 225

27.7 The Future for Biologics LCM 226

27.7.1 Legal Strategies in the United States 227

27.7.2 Indication Expansion in Europe 228

27.7.3 Brand Loyalty Programs and Services 229

27.8 The Emergence of the "Innovasimilar" Biopharma Company 229

27.9 Final Words 231

Part G The Integrated Brand LCM Strategy And its Implementation 233

28. Strategic Goals of LCM Brand Plans 235

28.1 Position to Market 235

28.2 Comparative Clinical Profile versus Gold Standard 237

28.3 Level of Market Unmet Need 237

29. Ten Keys to Successful LCM 238

29.1 Excellent Functional Expertise 238

29.1.1 Patent Attorneys 239

29.1.2 Regulatory Affairs 240

29.1.3 Clinical Development 240

29.1.4 Formulation Scientists 241

29.1.5 Marketing and Sales 242

29.1.6 Manufacturing 243

29.2 Visible Management Support 244

29.3 Unambiguous Ownership 245

29.4 An Early Start 246

29.5 A Robust "Broad to Bespoke" Process 248

29.6 Focus on "High LCM Value Brands" 249

29.7 Adequate Resources 250

29.8 Measurements and Rewards 250

29.9 Training and Support 252

29.10 Realism 252

30. Organizational Structures and Systems for Ensuring Successful LCM 254

30.1 Organization of Project and Brand Management 254

30.1.1 Functional Structure 255

30.1.2 Project Structure 255

30.1.3 Matrix Structure 257

30.2 Project and Brand LCM Structures 259

30.3 LCM Center of Excellence 263

30.4 Composition of the LCM CoE 266

31. The LCM Process: Description, Timing, and Participants 268

31.1 Purpose of the LCM Process 268

31.2 Timing of the LCM Process 269

31.3 Description of the LCM Process 271

Part H Integrating LCM with Portfolio Management 277

32. Principles of Portfolio Management 279

33. LCM Projects in the Development Portfolio 284

34. Managing Established Brand Portfolios 286

34.1 What Do You Do with a Priority Established Brand? 288

34.2 What about the Nonpriority Brands? 289

34.3...