Pharmaceutical Anti-Counterfeiting

MARK DAVISON, CEO of Blue Sphere Health, is a pharmaceutical consultant and entrepreneur with more than twenty years of industry experience. He was formerly business development director for healthcare at SICPA, one of the world's leading anti-counterfeiting and product security technology providers, where he gained an in- depth, global perspective on counterfeit pharmaceuticals and medical devices. He is a writer, seminar leader, and international conference speaker on pharmaceutical security matters. His article "Drugs for the Developing World: Obligation, Opportunity and Threat" won the Royal Society of Medicine Oswald Morton Essay Prize in 2010.

• PREFACE xxi ACKNOWLEDGMENTS xxiiiPART 1 GENERAL THEMES1 Introduction 3Why Write This Book? 3Doesn’t This Book Just Help the Criminals? 4Who Is the Book Aimed At? 52 Origins and Context of Counterfeiting in Healthcare 7Background and Nature of the Threat 7R&D Costs, Patent Life, and the Profit Imperative 9A Low Cost, High Profit Business 10Research and Development 10Regulatory Approval 10Manufacturing 11Packaging 11Marketing 11Logistics 12Permissive Legal Environment 12Role of the Internet 13Global Growth of Counterfeiting 143 A Snapshot of the Problem 15Case Study: Malaria 184 Risks and Costs of Counterfeit Pharmaceuticals 21Risks and Costs for Consumers 21The Drugs Do Not Work 21Toxic Products 23Fear and Mistrust of the Medical Profession 24Risks and Costs for Businesses 24Revenue Loss 24Brand Erosion 28Litigation 30Loss of Public Trust 30Risks and Costs for Governments 31Public Concern 31Increased Social and Healthcare Costs 32Tension between Affordability and Quality 34Increased Regulatory Costs 345 Anti-Counterfeiting Definitions 35Terminology and General Principles 36Counterfeiting 38Diversion 45Parallel Trade and Re-Importation 466 Protecting and Educating Consumers 49Consumer Behavior 49Engagement with the Consumer 50Engaging Through Social Media 51Social Networking and Blogging as Anti-Counterfeiting Tools 52Consumer-Focused Authentication Technology 54Cultural Sensitivity 557 Business Risks and Strategy 57Establishing a Baseline and Prioritizing At-Risk Products 59Doing the Simple Things 60Used Manufacturing Equipment 61Layering of Countermeasures 62Information Management and "Need-To-Know" 62Integration with Corporate Strategy 638 Government Issues 65Legal Framework 66Link with Reimbursement and Social Healthcare 68Law Enforcement Issues 69Data Mining 69Money Transfer and Credit Cards 70Internet Service Providers and Search Engines 719 Intellectual Property and Anti-Counterfeiting 73Establishing Ownership of Intellectual Property Rights (IPR) 74Patents 74Patenting of Security Technologies 75Trademarks 75Online Intellectual Property 78Criminal Prosecution Versus Civil Suit 7910 Traceability or Authentication? 81PART 2 AUTHENTICATION11 What Is Authentication? 87Digital Versus Sensory Authentication 88Types of Authentication Technologies 89International Standards and Norms 9112 Authentication of the Person 9313 Authentication of Bulk Products 9714 On-Dose and In-Dose Authentication 103On-Dose Features 104In-Dose Features 106Regulatory Reporting 109Labeling and Disclosure of On-Dose and In-Dose Approaches 110Concealment of Identity 110On-Product and In-Product Approaches Aimed at Consumers 111Formulation Additives in Products other than SODFs 11215 Analytical Detection of Counterfeit Dosage Forms 113Simple Chemical and Physical Analysis Methods 114Colorimetry 115Hardness and Dissolution Tests 115Thin Layer Chromatography (TLC) 116Ultraviolet and Visible Spectroscopy 117Laboratory-Based Methods 118Atomic Absorption Spectrophotometry (AAS) 118X-ray Techniques 119Nuclear Magnetic Resonance (NMR) Spectroscopy 119Mass Spectrometry (MS) 120Gas Chromatography (GC) 120Liquid Chromatography (LC) 121Capillary Electrophoresis (CE) 121Forensic Palynology 121Non-Destructive Methods 123X-ray Diffraction 123Infrared Spectroscopy 123Fourier Transform Infrared (FTIR) Spectroscopy 124Near-Infrared (NIR) 125Raman Spectroscopy 125Terahertz Imaging 126Conclusions on the Analysis of Dosage Forms 12616 The Role of Packaging 127Packaging Design 128Being Just Slightly Better than the Opposition 130Security Features on Packaging 131Integration into Packaging: Bulk Packaging Material at Source 131Integration into Packaging: By Design Complexity 132Addition to Packaging: Labels, Printed Packaging, etc. 13217 Printing Technologies 135Offset Lithography 135Flexography 136Gravure 136Screen Printing 137Laser Printing 137Clichéor Pad Printing 138Embossing and Debossing 138Laser Engraving 138Inkjet Printing 138Some Technical Considerations 140How Much Surface Area Is Availablefor the Feature? 140What Is the Budget? 141Is the Product Surface Flat or Curved? 141Is the Product Orientation Predictable and Constant? 142How Much Time Is Available? 142Direct Application onto Packaging Versus Use of Labeling 14318 Security Labels 145Adhesive 146Frangibility 147Security Cuts and Perforation 148Voiding 148Alignment 149General Considerations 149Label Reconciliation and Storage Conditions 15119 Holograms and DOVIDs 153Types of Holograms 154Other Optically Variable Devices 15620 Specialty Inks 159Colorshift Inks 160Other Security Inks 161Iridescent 161Metallic 162Fluorescent 162Bi-fluorescent 162Thermochromic 163Photochromic 163Coin Reactive 163Microstructured Taggants 16321 Covert Taggants and Forensic Markers 165Infrared-Absorbing Inks 165Forensic Markers 166Isotopic Tags 167DNA Markers 167Antibody Systems 168X-Ray Detection of Specific Added Elements 168Other Markers 16822 General Conclusions on Printed Packaging and Security Labels 169Layering 169Guidelines 170Flexibility and Vigilance 17023 Security of Primary Packaging 173Contact with Dosage Form 173Types of Primary Packaging 175Blister Packs 175Wallets, Carded Blisters, Compliance-Prompting Packaging, etc. 179Strip Packs, Sachets, and Pouches 180Bottles or Jars 181Tubes 183Vials and Ampoules 184Other Dosage Forms 187Syringes 187Inhalers and Related Devices 187Implantable Drug-Containing Devices 189Equipment and Consumables for Diagnostic Products 189Medical Devices 190Analytical Considerations for Primary Packaging 19124 Security of Secondary Packaging 193Role of Secondary Cartons 193Outsourced or In-House Application 196Outsourced Security Features 198In-House Security Application 198Planning Ahead 199Tamper-Evidence: Seals, Shrink Wraps, Pack Closures, and Adhesive 200Definitions 200Snap-Off Caps 200Glued End-Flaps 201Seals 201Induction Seals 203Shrink Wrap and Tear Tape 20325 Analytical Methods for Packaging 205Visual Inspection (Visible Light) 206Other Optical Methods (UV, IR, Polarized Light) 207Other Methods 20726 Security of Other Packaging Types 209Drug–Device Combinations 209Patient Information Leaflets and Labels 211Other Documentation 212Certificates of Analysis, Import Licenses, etc. 212Prescriptions 213Reimbursement 21327 Bulk Packaging and Transport Security 215Theft of Cargo from Trucks and Warehouses 216Vigilance 218Information Management 218Training 218Other Factors 219Technology Approaches: RFID and GPS 219Radio Frequency Identification (RFID) Technology 219Global Positioning System (GPS) Technology 220PART 3 PRODUCT TRACKING28 Rationale for Pharmaceutical Tracking 22529 Tracking Technologies 231Serial Numbers 232Linear Bar Codes 234Matrix Codes 2342D Codes and Mobile Phones 236Technical Issues with 2D Codes 237Radio Frequency Identification (RFID) 238Mobile Phones 242Other Tracking Technologies 244Applicability of Tracking Systems Worldwide 24530 Data Format, Generation, and Storage 247Serialization 247Randomization 250Pedigree/ePedigree 251Track and Trace 253Fingerprinting 254Physical Authentication + Digital Tracking = Enhanced Security 25631 Management of Packaging Hierarchy 257Inference Approaches 257"Bookend" Approaches 262Batch Level Traceability Versus Full Serialization 266Digital Signatures 266Supply Chain Benefits 26632 Geographical Perspectives 269U.S. State Laws 269California 270Federal Initiatives in the United States 271Europe 273The Concept of "Medicrime" 275European Committee on Crime Problems (CDPC) 275Purpose 276Scope 276Definitions 276Manufacturing of Counterfeits 278Supplying, Offering to Supply, and Trafficking in Counterfeits 278Falsification of Documents 279Similar Crimes Involving Threats to Public Health 279Aiding or Abetting and Attempt 279Jurisdiction 280Corporate Liability 281Sanctions and Measures 281Aggravating Circumstances 282Criminal Investigations 282Cooperation and Information Exchange 283Measures for Prevention 283Measures for Protection 284International Cooperation 284Monitoring Mechanism 284EFPIA Pilot Coding Project 285India 287Malaysia Meditag System 288Turkey 289Brazil 29033 Product Tracking in Other Industries 291Excise Products: Tobacco and Alcohol 291Food and Beverage 292Toys 293Conclusions 29434 Supply Chain Security Processes 295General Security 295Forward Logistics 296Reverse Logistics: Returns and Customer Complaints 297Insider Fraud 298Security of Security Materials 301Security of Evidence 30235 Implementing Anti-Counterfeiting Initiatives—Practical Issues 303How to Work Together: Getting the Best from Security Partnerships 303What Do Pharmaceutical Companies Need? 304What Do Security Suppliers Need? 305What Do Print and Packaging Suppliers Need? 306General Observations on Business Models for Product Security 307Unit Fee Pricing 308Commodity Pricing 308Insurance Premium 309Other Pharmaceutical Service Industries 309PART 4 CONCLUSIONS AND THE FUTURE36 Where Do We Go from Here? 313Future Scenario: Risk of Inaction 313Future Scenario: Risk of Incomplete Action 314Future Scenario: Risk of Inappropriate Action 314Future Policy Approaches 315Future Authentication Approaches 317Future Traceability Approaches 318Global Standards, Worldwide Tracking 318RFID 319GPS 31937 New Models, New Approaches 321Non-Technological Approaches 322Lack of Availability of Genuine Drugs 323Huge Profit Potential 323Low Entry Costs 324Law Enforcement Issues 324Legal Approaches 324Conclusions 32538 Selected Examples from Around the World 329Argentina 329Brazil 330Canada 330China 330European Union 331India 331Laos and Southeast Asia 331Nigeria 331Russia 332Uganda/East Africa 332United Kingdom 333United States 333PART 5 FURTHER RESOURCESA PATIENT’S GUIDE TO AVOIDING COUNTERFEIT DRUGS 337Do I Need This Particular Medication? 337Is My Desired Drug Approved and Available in My Country? 338Are My Drug Sources and Methods of Purchase Safe? 338What Does the Packaging Look Like? 339What Does the Product Itself Look Like? 340When Taking the Drug 341After Taking the Drug 341NOTES AND REFERENCES 343GLOSSARY 363INFORMATION SOURCES 379General Readership 379Specialist Readership 380News 381Education 381Organizations 381DRUG REGULATORS 385INDEX 391

“The book is an excellent resource and I would recommend it to anyone with either an interest in anti-counterfeiting technology or pharmaceutical counterfeiting in general.”   (International Journal of Comparative and Applied Criminal Justice, 26 April 2012)"Pharmaceutical Anti-Counterfeiting" covers the key concepts and explains the available options in pharmaceutical anti-counterfeiting including a mix of policy, strategy, tactics and practical implementation tips. A must-read for those determined to do something about counterfeit pharmaceutical and healthcare products, and will prove useful to brand protection professionals in other industries." (Chemanager, 24 January 2012)"For those determined to take an action against counterfeit pharmaceutical and healthcare products, will find the book useful." (The Holography Times, 1 December 2011)"Using accessible and interesting language, Mark Davison talks the reader right the way through the issue of drug counterfeiting - its origins and context within healthcare , the risks presented to companies and consumers alike, anti-counterfeiting strategies and technologies - the result being a definitive guide to the inner workings of the counterfeit industry and a myriad of ways to stymie the counterfeiter's every step ... Reading this book will provide any pharmaceutical brand owner with a solid and informed grounding for making any decisions related to anti-counterfeiting strategy." (Notofakes.com, 16 November 2011)"In writing this book Davison has made a great contribution to the global fight against counterfeit drugs. For the first time we have a single reference that collects explanations of every significant anti-counterfeiting technology and approach used around the globe, including both sensory authentication and traceability technologies." (RxTrace, September 2011)"Best Pharma Anit-Counterfeiting Book Ever...Davison does not back away from or avoid pointing out conflicts and disagreements that exist between approaches to solving problems (digital vs. physical authentication), but he is quick to help the reader find the strongest solution by seeing the ways that solutions and technologies can work together." (Randall Burgess, Pharmaceutical AntiCounterfeiting Blog, October 5, 2011)"Pharmaceutical Anti-Counterfeiting: Combating the Real Danger from Fake Drugs by Mark Davison succeeds in providing a handbook for professionals involved in product security and brand protection. . . Davison has a great deal of industry experience in pharmaceuticals as well as product security and is well positioned and qualified to be the one to write this book. The industry owes him a debt of gratitude for committing himself to this effort." (Pharma AntiCounterfeiting News, 1 August 2011)"Cambridge-based consultant and entrepreneur Mark Davison, CEO of Blue Sphere Health Ltd, has written a comprehensive guide for drug company executives, technology vendors, healthcare professionals and policy-makers. . . This newly-released 426pp volume is a must-read primer for those determined to do something about counterfeit pharmaceutical and healthcare products, and will prove useful to brand protection professionals in other industries." (Cambridge Network , 6 September 2011)