Foreword xi Preface xv Acknowledgments xvii Introduction 1 Setting a Transformative Agenda 1 What Should You Expect to Take Away from This Book? 2 Book Format 3 Who Should Benefit from Reading This Book? 5 Research Methodology 6 A Positive View of the Future 6 More Than a Generation of Change Will Be Required 7 References 7 Section I The Pharmaceutical Industry and Its Supply Chain 9 1 Industry Basics 11 Pharmaceutical Products 11 Industry Business Models and the Supply Chain 12 References 20 2 The Pharmaceutical Supply Chain 21 The End-to-end (E2E) Supply Chain in Perspective 21 Production Supply Chain: Small Molecule Products (Originator and Generic) 21 Production Supply Chain: Biologic Products (Originator and Biosimilar) 24 Production Supply Chain: Advanced Therapies--Autologous 30 References 36 3 Regulation of Pharmaceutical Products 39 Regulatory Authorities 39 Licensing Medicinal Products for Sale 40 Electronic Common Technical Document 41 Drug Development Programs 42 Regulatory Good Practices (GxP) 43 Expert Witness Statement: Alan Kennedy 48 Regulatory Modernization Initiatives 52 References 62 4 Evidence of Serious Supply Chain Problems Emerge 65 U.S. Government Accountability Office Sounds an Important Warning Bell 65 The Heparin Tragedy 67 FDA/Xavier University Co-sponsored Global Outsourcing Conference (GOC) 68 Governments and Regulatory Authorities Respond 71 References 78 5 Investigating Worrying Supply Chain Symptoms 81 Large Pharmaceutical Companies Outsource Their Assets 81 The Valley of Death Creates the Patent Cliff 85 Merger and Acquisition Becomes the Next Strategic Realignment 85 The Emergence of Biologics (eg Monoclonal Antibodies) 87 Commercial Potential of Recombinant DNA 88 What Is the Purpose of the Orphan Drug Act? 91 Value-based Pricing and HEOR Groups Emerge 92 Symptoms Transition to Deep Concerns 98 References 104 6 Impact of the Systems Dynamic on Supply Chain Performance 107 Circling Back to Professor Andrew Cox''s Assessment 107 Supply Chain Underperformance Through the Development Process 108 Differences Between the Commercial and Clinical Supply Chain Challenges 112 Commercial Launch and Supply (and Phase IV--Clinical Trials After Launch) 115 7 The Outcome 119 Politicians Have Been Calling Out the Spiraling Price of Drugs 119 Wildly Varying Estimates of Drug Development Costs and Clinical Trial Failures 119 Generic Drugs Are Not Always the Same as the Originator''s 120 Animal Testing Is Still the Only Way 121 Me-too Drugs 122 Patient-centricity Is About Brands Not Cures 122 Counterfeit Drugs 123 Price Gouging 123 Is Big Pharma Becoming More Focused on the Patient These Days? 124 Does the Industry Overlook Side Effects? 124 Expert Witness Statement: Dr Ray Perkins 125 Do Genes Define Our Biological and Medical Destiny? 129 Of Missing Methods, Moldy Models, Mutated Mindsets, and Muddled Medications 131 To Ship or Not to Ship? That Is the Question 133 Basic Assumptions in the Pharmaceutical Industry 135 Impact of Basic Assumptions 138 An Expert Witness Statement: Professor Daniel Steenstra 138 What Is a Paradigm Shift? 139 References 141 Section II Managing the Supply Chain Strategically 143 8 Introduction to Socio-technical Systems 145 What is a System? 145 Closed and Open Systems 145 The Socio-technical System 147 Systems Complexity in the Supply Chain: Bullwhip Effect 153 Example of a High-performing Socio-technical (Production) System 154 References 155 9 Fundamentals of the Supply Chain 157 What Is a Supply Chain? 157 The Supply Chain in Modern Times 158 Three States in the Supply Chain 159 Reference 160 10 The Supply Chain and Competitive Edge 161 Supply Chains, Not Products, Compete 161 Linking Porter''s Value Chain Model to the Supply Chain System 164 Expert Witness Statement: Nick Rich, PhD, Professor in Operations Management, Business, at Swansea University 167 References 169 11 Core Disciplines of Supply Chain Management 171 Planning and Inventory Management 171 Strategic Procurement 189 Transport Logistics 197 References 209 12 Support Disciplines of Supply Chain Management 211 Information Systems (IS) and Information Technology (IT) 211 Industrial Improvement 219 Expert Witness--Javid Cheema 226 Leadership and Culture in the Supply Chain 239 References 255 Section III Transforming the Pharmaceutical Supply Chain 257 13 Shifting the Paradigm Gear 259 Why Change? 259 Underpinning Principles of the New Paradigm 261 Time to Switch on Your Imagination 263 Aviation as a Comparator with Pharmaceuticals 265 Redefining Basic Assumptions for the New Paradigm 266 References 268 14 Heuristic Methodology to Define the Transformation 269 Primary Analysis 270 Supporting Evidence 270 Small Molecule Product Supply Chain 270 Primary Analysis 270 Supporting Evidence 271 Confirmatory Supporting Evidence 273 Cimetidine--More Confirmatory Supporting Evidence 275 Biologic Product Supply Chain (Including Allogeneic Products) 279 Overview 283 Manufacturing Capability 283 References 284 15 Introducing the Pharmaceutical Production System 285 Drugs Are Physical Products 285 A New Model for Product Development 287 Adopting Production Systems Principles in Hospitals 291 References 293 16 Catalyst of Radical Change 295 The First Step 295 Criteria for Patentability: New and Useful Process 296 The Patent Came After the Process 296 What Is Compound Claims Patent Law? [2] 297 What Is the Purpose of Patent? 298 Compound Claims for New Molecules 299 Patent Law Moves Center Stage 300 Previous and Ongoing Patent Change Initiatives 300 References 304 17 Delivering the Transformation with Stakeholders Onboard 305 Returning to Purpose 305 What Can Key Stakeholders Do to Help? 310 Governments 310 Regulatory Authorities 313 Clinicians in the Healthcare System 314 Investors in Drug Development 315 Universities and Colleges 315 Patients 317 Key Stakeholder Groups Inside the Pharmaceutical Supply Chain 317 Engaging Pharmaceuticals in Supply Chain Management (SCM) 320 More than a Generation of Change Is Required 320 References 321 Appendices 323 Index 341.