Pharmaceutical Anti-Counterfeiting

PREFACE xxi ACKNOWLEDGMENTS xxiii PART 1 GENERAL THEMES 1 Introduction 3 Why Write This Book? 3 Doesn't This Book Just Help the Criminals? 4 Who Is the Book Aimed At? 5 2 Origins and Context of Counterfeiting in Healthcare 7 Background and Nature of the Threat 7 R&D Costs, Patent Life, and the Profit Imperative 9 A Low Cost, High Profit Business 10 Research and Development 10 Regulatory Approval 10 Manufacturing 11 Packaging 11 Marketing 11 Logistics 12 Permissive Legal Environment 12 Role of the Internet 13 Global Growth of Counterfeiting 14 3 A Snapshot of the Problem 15 Case Study: Malaria 18 4 Risks and Costs of Counterfeit Pharmaceuticals 21 Risks and Costs for Consumers 21 The Drugs Do Not Work 21 Toxic Products 23 Fear and Mistrust of the Medical Profession 24 Risks and Costs for Businesses 24 Revenue Loss 24 Brand Erosion 28 Litigation 30 Loss of Public Trust 30 Risks and Costs for Governments 31 Public Concern 31 Increased Social and Healthcare Costs 32 Tension between Affordability and Quality 34 Increased Regulatory Costs 34 5 Anti-Counterfeiting Definitions 35 Terminology and General Principles 36 Counterfeiting 38 Diversion 45 Parallel Trade and Re-Importation 46 6 Protecting and Educating Consumers 49 Consumer Behavior 49 Engagement with the Consumer 50 Engaging Through Social Media 51 Social Networking and Blogging as Anti-Counterfeiting Tools 52 Consumer-Focused Authentication Technology 54 Cultural Sensitivity 55 7 Business Risks and Strategy 57 Establishing a Baseline and Prioritizing At-Risk Products 59 Doing the Simple Things 60 Used Manufacturing Equipment 61 Layering of Countermeasures 62 Information Management and "Need-To-Know" 62 Integration with Corporate Strategy 63 8 Government Issues 65 Legal Framework 66 Link with Reimbursement and Social Healthcare 68 Law Enforcement Issues 69 Data Mining 69 Money Transfer and Credit Cards 70 Internet Service Providers and Search Engines 71 9 Intellectual Property and Anti-Counterfeiting 73 Establishing Ownership of Intellectual Property Rights (IPR) 74 Patents 74 Patenting of Security Technologies 75 Trademarks 75 Online Intellectual Property 78 Criminal Prosecution Versus Civil Suit 79 10 Traceability or Authentication? 81 PART 2 AUTHENTICATION 11 What Is Authentication? 87 Digital Versus Sensory Authentication 88 Types of Authentication Technologies 89 International Standards and Norms 91 12 Authentication of the Person 93 13 Authentication of Bulk Products 97 14 On-Dose and In-Dose Authentication 103 On-Dose Features 104 In-Dose Features 106 Regulatory Reporting 109 Labeling and Disclosure of On-Dose and In-Dose Approaches 110 Concealment of Identity 110 On-Product and In-Product Approaches Aimed at Consumers 111 Formulation Additives in Products other than SODFs 112 15 Analytical Detection of Counterfeit Dosage Forms 113 Simple Chemical and Physical Analysis Methods 114 Colorimetry 115 Hardness and Dissolution Tests 115 Thin Layer Chromatography (TLC) 116 Ultraviolet and Visible Spectroscopy 117 Laboratory-Based Methods 118 Atomic Absorption Spectrophotometry (AAS) 118 X-ray Techniques 119 Nuclear Magnetic Resonance (NMR) Spectroscopy 119 Mass Spectrometry (MS) 120 Gas Chromatography (GC) 120 Liquid Chromatography (LC) 121 Capillary Electrophoresis (CE) 121 Forensic Palynology 121 Non-Destructive Methods 123 X-ray Diffraction 123 Infrared Spectroscopy 123 Fourier Transform Infrared (FTIR) Spectroscopy 124 Near-Infrared (NIR) 125 Raman Spectroscopy 125 Terahertz Imaging 126 Conclusions on the Analysis of Dosage Forms 126 16 The Role of Packaging 127 Packaging Design 128 Being Just Slightly Better than the Opposition 130 Security Features on Packaging 131 Integration into Packaging: Bulk Packaging Material at Source 131 Integration into Packaging: By Design Complexity 132 Addition to Packaging: Labels, Printed Packaging, etc. 132 17 Printing Technologies 135 Offset Lithography 135 Flexography 136 Gravure 136 Screen Printing 137 Laser Printing 137 Clicheor Pad Printing 138 Embossing and Debossing 138 Laser Engraving 138 Inkjet Printing 138 Some Technical Considerations 140 How Much Surface Area Is Available for the Feature? 140 What Is the Budget? 141 Is the Product Surface Flat or Curved? 141 Is the Product Orientation Predictable and Constant? 142 How Much Time Is Available? 142 Direct Application onto Packaging Versus Use of Labeling 143 18 Security Labels 145 Adhesive 146 Frangibility 147 Security Cuts and Perforation 148 Voiding 148 Alignment 149 General Considerations 149 Label Reconciliation and Storage Conditions 151 19 Holograms and DOVIDs 153 Types of Holograms 154 Other Optically Variable Devices 156 20 Specialty Inks 159 Colorshift Inks 160 Other Security Inks 161 Iridescent 161 Metallic 162 Fluorescent 162 Bi-fluorescent 162 Thermochromic 163 Photochromic 163 Coin Reactive 163 Microstructured Taggants 163 21 Covert Taggants and Forensic Markers 165 Infrared-Absorbing Inks 165 Forensic Markers 166 Isotopic Tags 167 DNA Markers 167 Antibody Systems 168 X-Ray Detection of Specific Added Elements 168 Other Markers 168 22 General Conclusions on Printed Packaging and Security Labels 169 Layering 169 Guidelines 170 Flexibility and Vigilance 170 23 Security of Primary Packaging 173 Contact with Dosage Form 173 Types of Primary Packaging 175 Blister Packs 175 Wallets, Carded Blisters, Compliance-Prompting Packaging, etc. 179 Strip Packs, Sachets, and Pouches 180 Bottles or Jars 181 Tubes 183 Vials and Ampoules 184 Other Dosage Forms 187 Syringes 187 Inhalers and Related Devices 187 Implantable Drug-Containing Devices 189 Equipment and Consumables for Diagnostic Products 189 Medical Devices 190 Analytical Considerations for Primary Packaging 191 24 Security of Secondary Packaging 193 Role of Secondary Cartons 193 Outsourced or In-House Application 196 Outsourced Security Features 198 In-House Security Application 198 Planning Ahead 199 Tamper-Evidence: Seals, Shrink Wraps, Pack Closures, and Adhesive 200 Definitions 200 Snap-Off Caps 200 Glued End-Flaps 201 Seals 201 Induction Seals 203 Shrink Wrap and Tear Tape 203 25 Analytical Methods for Packaging 205 Visual Inspection (Visible Light) 206 Other Optical Methods (UV, IR, Polarized Light) 207 Other Methods 207 26 Security of Other Packaging Types 209 Drug-Device Combinations 209 Patient Information Leaflets and Labels 211 Other Documentation 212 Certificates of Analysis, Import Licenses, etc. 212 Prescriptions 213 Reimbursement 213 27 Bulk Packaging and Transport Security 215 Theft of Cargo from Trucks and Warehouses 216 Vigilance 218 Information Management 218 Training 218 Other Factors 219 Technology Approaches: RFID and GPS 219 Radio Frequency Identification (RFID) Technology 219 Global Positioning System (GPS) Technology 220 PART 3 PRODUCT TRACKING 28 Rationale for Pharmaceutical Tracking 225 29 Tracking Technologies 231 Serial Numbers 232 Linear Bar Codes 234 Matrix Codes 234 2D Codes and Mobile Phones 236 Technical Issues with 2D Codes 237 Radio Frequency Identification (RFID) 238 Mobile Phones 242 Other Tracking Technologies 244 Applicability of Tracking Systems Worldwide 245 30 Data Format, Generation, and Storage 247 Serialization 247 Randomization 250 Pedigree/ePedigree 251 Track and Trace 253 Fingerprinting 254 Physical Authentication + Digital Tracking = Enhanced Security 256 31 Management of Packaging Hierarchy 257 Inference Approaches 257 "Bookend" Approaches 262 Batch Level Traceability Versus Full Serialization 266 Digital Signatures 266 Supply Chain Benefits 266 32 Geographical Perspectives 269 U.S. State Laws 269 California 270 Federal Initiatives in the United States 271 Europe 273 The Concept of "Medicrime" 275 European Committee on Crime Problems (CDPC) 275 Purpose 276 Scope 276 Definitions 276 Manufacturing of Counterfeits 278 Supplying, Offering to Supply, and Trafficking in Counterfeits 278 Falsification of Documents 279 Similar Crimes Involving Threats to Public Health 279 Aiding or Abetting and Attempt 279 Jurisdiction 280 Corporate Liability 281 Sanctions and Measures 281 Aggravating Circumstances 282 Criminal Investigations 282 Cooperation and Information Exchange 283 Measures for Prevention 283 Measures for Protection 284 International Cooperation 284 Monitoring Mechanism 284 EFPIA Pilot Coding Project 285 India 287 Malaysia Meditag System 288 Turkey 289 Brazil 290 33 Product Tracking in Other Industries 291 Excise Products: Tobacco and Alcohol 291 Food and Beverage 292 Toys 293 Conclusions 294 34 Supply Chain Security Processes 295 General Security 295 Forward Logistics 296 Reverse Logistics: Returns and Customer Complaints 297 Insider Fraud 298 Security of Security Materials 301 Security of Evidence 302 35 Implementing Anti-Counterfeiting Initiatives-Practical Issues 303 How to Work Together: Getting the Best from Security Partnerships 303 What Do Pharmaceutical Companies Need? 304 What Do Security Suppliers Need? 305 What Do Print and Packaging Suppliers Need? 306 General Observations on Business Models for Product Security 307 Unit Fee Pricing 308 Commodity Pricing 308 Insurance Premium 309 Other Pharmaceutical Service Industries 309 PART 4 CONCLUSIONS AND THE FUTURE 36 Where Do We Go from Here? 313 Future Scenario: Risk of Inaction 313 Future Scenario: Risk of Incomplete Action 314 Future Scenario: Risk of Inappropriate Action 314 Future Policy Approaches 315 Future Authentication Approaches 317 Future Traceability Approaches 318 Global Standards, Worldwide Tracking 318 RFID 319 GPS 319 37 New Models, New Approaches 321 Non-Technological Approaches 322 Lack of Availability of Genuine Drugs 323 Huge Profit Potential 323 Low Entry Costs 324 Law Enforcement Issues 324 Legal Approaches 324 Conclusions 325 38 Selected Examples from Around the World 329 Argentina 329 Brazil 330 Canada 330 China 330 European Union 331 India 331 Laos and Southeast Asia 331 Nigeria 331 Russia 332 Uganda/East Africa 332 United Kingdom 333 United States 333 PART 5 FURTHER RESOURCES A PATIENT'S GUIDE TO AVOIDING COUNTERFEIT DRUGS 337 Do I Need This Particular Medication? 337 Is My Desired Drug Approved and Available in My Country? 338 Are My Drug Sources and Methods of Purchase Safe? 338 What Does the Packaging Look Like? 339 What Does the Product Itself Look Like? 340 When Taking the Drug 341 After Taking the Drug 341 NOTES AND REFERENCES 343 GLOSSARY 363 INFORMATION SOURCES 379 General Readership 379 Specialist Readership 380 News 381 Education 381 Organizations 381 DRUG REGULATORS 385 INDEX 391