Pharmaceutical Anti–Counterfeiting – Combating the Real Danger from Fake Drugs

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