WEC – IEF - European Roundtable Darmstadt, October 26-27, 2006, Dr. Heike Bockholt

1. WEC – IEF - European RoundtableDarmstadt, October 26-27, 2006, Dr. Heike Bockholt Securing the pharmaceutical supply chain: Anti-Counterfeiting - a manufacturer’s perspective Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

2. Fake industry is growing… Ca. 80% Counterfeits Can everbody print money? NO! Can everybody print pharmaceutical packaging material? YES! Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

3. Counterfeits in the markets • ~ 10% of pharmaceuticals in the global markets are counterfeits • Estimations: • 2% in Western Europe and USA • 25 – 50 % in developing countries Illegal Internet trade main challenge of the future! Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

4. What is counterfeited? • All products with high market potential: • High value • High volume • Drugs to be determined for the „normal supply chain“ • Drugs to be determined for the black market (anabolics) Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

5. Incorrect Ingredient 16% Incorrect amount 17% No active Ingredient 60% Correct Ingredient 7% Counterfeits: WHO Definition • A counterfeit medicine is one which is deliberately and fraudulently mislabelled with respect to identity and/or source. Percentagebreakdown of dataon 325 of 771 cases of substandard drugs including antibiotics, antimalarials and antituberculosis drugs reported from around the world to WHO database Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

6. Counterfeits manufactured in Asia for RoW across branches Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

7. Latinamerica main source of counterfeits for US, EU, Russia Drugs only Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

8. Risks Nigeria: faked meningitis vaccine: 2500 dead • Damage to Public Health • Erosion of Patient Confidence • Detriment of Company Reputation • Potential Liabilities • Revenue Lost Haiti:diethyleneglycole contaminated Syrup: 89 dead Haiti: faked malaria drug 59 dead USA: Lipitor faked UK: Tamiflu faked Internat. Counterfeit market: 35 Mrd. US-$ USA:Zyprexa replaced by ASS Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

9. 5 elements of Anti-Counterfeiting concepts Legal Framework • Requirements • Control • Reporting • Prosecution International Collaboration • WHO REACT • WTO IPR Groups • WCO Interpol • TRIPS PSI, … Manufacturer • Policy • Prevention of unauthorized access to products and production equipment • Application of security features • Reporting, Investigation • Control Material Flow / (Track and Trace) • Inspection / Audit • Authentication Supply Chain Customer • Awareness • Education • Authentication Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

10. Combat counterfeits at Boehringer Ingelheim • 1998 Member of PSI (Pharmaceutical Security Institute) • 2001 Corporate Policy & Rapid Reporting • 2003 Pilot project: overt-covert security features • 2004 internal • Rules to prevent unauthorized access to machines and products • external • Chairing the EFPIA* Anticounterfeiting ad hoc group • 2005 Regional forensicprojects • 2006 Product Identification Standard • * EFPIA = European Federation of Pharmaceutical Industries Associations • BI- Project team • Quality (Lead) • Legal • Marketing • Production • Supply Chain Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

11. a a The toolbox for product protection • Overt features: • Visual Inspection: • Colour shifting inks • Holograms • Embossing • Watermarks • Tamper proof packaging • Coding: • Unique identifier/pack: • Authentication at • point of dispensing • Track and Trace • Covert features/ • simple verification • Luminescent effects (UV) • Microprinting • Thermocromics secure pack secure pack nano PHARMA SECURE x23A45yQ1 • Covert features/ • Reading device • Infrared • Phosphorescence • Chemical Coding • DNA color shifting seal Microschrift  01800 – 77 00 • Identification: • Consumer • Pharmacist • Customs • Third parties • Forensic features: • Bio-Coding • Molecular coding • Taggants • Spectral analysis • Gas chromatography Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

12. covert ? Technical support overt Patient Authentication complex simple The Dilemma safe DNA Combination Overt/covert & Track & Trace Chemical marker microprint Nano tech Product Pro- tection Hologram Color shifting ink unsafe Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

13. „The pharmaceutical industry develops drugs • using billions of Dollars • and they distribute them • like oranges“ US reporter, 2003 Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

14. Counterfeit penetration by irregular & uncontrolled Supply Chain x x x x x API Manufacturer today: Certified & Audited Distribution 20 – 50 steps Incl. customs QC Point of dispensing Excipients Repackager Customer Packaging Material Internet Supply Chain Control Legal Supply Chain Security features Track& Trace: Transparency & Prosecution Controlled Internet Supply Main authentication Reference to original code! Counterfeit resistant Auto ID-code Audited Supply Chain Control Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

15. Supply chain control - Principles • Audits/Certificationto ensure collaboration with reliable partners • Follow product flow by using Auto ID systems: • Authentication at point of dispensing • (Unique identifier, e.g. 2 D barcode) • Sufficient for identification of suspicious cases! • Track and Trace (e.g. using RFID-technology) • Supports identification of the weak point/penetration of counterfeits! • Facilitates e.g. recalls • Potentially additional advantages in distribution • Pedigree: Documentation of each step • Stakeholder • Manufacturer • Repackager • Wholesaler Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

16. Comparison of Auto-ID-Systems Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

17. USA May 04 • FDA-report „Combating counterfeit drugs“ • Support pedigreerequirements of different US-states • RegardRadio Frequency Identification (RFID) to establish electronic pedigree the most powerful tool to secure US drug supply • Implementation by 2007 expected • Slowdownin the progress towards adopting RFIDrealized! • Task force reassessed anti-counterfeiting efforts • Pedigreerequirementto becomeeffectiveDec. 06 • RFIDstill seen as promisingbutcurrently not mandatory June 06 Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

18. European Union • Authorities: • No common approach (-> different standards) • Some countries tighten legislation • Some countries require special labels (NO standard) Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

19. European Pharmaceutical Industry:EFPIA whitepaper • Health agencies must take responsibility for public health • Need to raise awareness of governments • Communication: get medicines from authorized sources only • Need for risk-based supply chain control incl. Manufacturer, Wholesaler + Distributor • Standards for product identification and packaging needed • Track + Trace, incl. • Authentication at point of dispensing • 2D – barcode as effective and affordable solution Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

20. Summary • USA/Europe: Clear trend towards enhanced supply chain control • Still open questions regarding • business processes • technical implementation/standards • data administration/privacy -> implementation timetable?! • RFID technology as mid to long term solution expected: • Will allow identication of penetration and might have further advantages • 2D barcodesas effective and affordableinterim solution (associations!) to cover primary risk (patient protection) • Different approach for countries where infrastructure does not support supply chain control needed Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

21. Thank you Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

22. Fighting against Counterfeits at Boehringer Ingelheim • Policy (2001): • Acknowledgment of the problem • Commitment to fight back • Corporate Procedure (2004): • Prevention of unauthorized access to products and production equipment • Risk assessment to check need for special product protection measures • Reporting Pilot-project Market Monitoring Participation in Industry groups Consultancy Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

23. Manufacturer - What to do? • Implementation of Policy and Procedures, covering: • Prevention of unauthorized access • to products and production equipment • Handling of Packaging Waste and Non Suitable for Use Finished Goods • Machine Trials • Machine Divestment • Control of Third Parties • Product protection: • Application of security features (based on risk assessment) • Internal Reporting • Investigations, Prosecution • Starting point for supply chain control Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable

24. Initiate Low density of information, unsuitable for mass serialization Inexpensive; infrastructure available Quality Risk Management Process (1D-barcode) High density of information, suitable for mass serialization Inexpensive; some adaptation of infrastructure needed Risk Assessment Manufact. Ident. Product class Batch data Random. Nr. Risk Identification No line of sight needed! -> read many items simultaneously Still too expensive, not mature, expensive infrastructure Risk Analysis Risk Evaluation Unaccep- n R table i o s i t k a Application of data carrier to c M i and/or and/or n Risk Control a u n a Risk Reduction m g m e o (item) (case) (pallet) m Risk Acceptance C e n k t s i T o Output / Results of the o l Quality Risk Management Process s Risk Review Review Events EPC, RFID, 2D-code, Track+ Trace, PedigreeAn overview (2D-barcode) Electronic product code (EPC) (RFID-tag) Authentication (origin check of item) Supply Chain Tracking: Following a physical good on the move Tracing: An authentication history record where a physical good has been Pedigree: The aggregate of documentation created for all objects Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable