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

Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable 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 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 Counterfeits: WHO Definition A counterfeit medicine is one which is deliberately and fraudulently mislabelled with respect to identity and/or source. No active Ingredient 60% Incorrect Ingredient 16% Incorrect amount 17% Correct Ingredient 7% Percentage breakdown of data on 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 Counterfeits manufactured in Asia for RoW across branches

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

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

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

Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable Combat counterfeits at Boehringer Ingelheim 1998Member of PSI (Pharmaceutical Security Institute) 2001Corporate Policy & Rapid Reporting 2003Pilot project: overt-covert security features 2004internal Rules to prevent unauthorized access to machines and products external Chairing the EFPIA* Anticounterfeiting ad hoc group 2005Regional forensic projects 2006Product 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 The toolbox for product protection Forensic features: Bio-Coding Molecular coding Taggants Spectral analysis Gas chromatography Coding: Unique identifier/pack: Authentication at point of dispensing Track and Trace Covert features/ simple verification Luminescent effects (UV) Microprinting Thermocromics Overt features: Visual Inspection: Colour shifting inks Holograms Embossing Watermarks Tamper proof packaging Covert features/ Reading device Infrared Phosphorescence Chemical Coding DNA Identification: Consumer Pharmacist Customs Third parties a nano a x23A45yQ1  – Microschrift

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

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

Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable Supply chain control - Principles 1.Audits/Certification to ensure collaboration with reliable partners 2.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 1D2DRFID* Electronic Product Code-compatible (= Global Standard) High density of information: Suitable for mass serialization No Line of sight needed: Bunchreading possible Upgradeable functionality (e.g. cooling chain) Inexpensive (current status) No major adaptation of infrastructure needed Technically mature (current status) Comparison of Auto-ID-Systems

Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable USA FDA-report „Combating counterfeit drugs“ Support pedigree requirements of different US-states Regard Radio Frequency Identification (RFID) to establish electronic pedigree the most powerful tool to secure US drug supply Implementation by 2007 expected Slowdown in the progress towards adopting RFID realized! Task force reassessed anti-counterfeiting efforts Pedigree requirement to become effective Dec. 06 RFID still seen as promising but currently not mandatory May 04 June 06

Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable 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 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 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 barcodes as effective and affordable interim 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 Thank you

Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable 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 Market MonitoringConsultancy Participation in Industry groups Pilot-project

Dr. Heike Bockholt Securing the pharmaceutical supply chain WEC-IEF-European Roundtable 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 EPC, RFID, 2D-code, Track+ Trace, Pedigree An overview High density of information, suitable for mass serialization Inexpensive; some adaptation of infrastructure needed Low density of information, unsuitable for mass serialization Inexpensive; infrastructure available No line of sight needed! -> read many items simultaneously Still too expensive, not mature, expensive infrastructure Application of data carrier to and/or (item)(case)(pallet) Manufact. Ident. Product class Batch data Random. Nr. Electronic product code (EPC) (RFID-tag) (2D-barcode) (1D-barcode) Authentication (origin check of item) 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 Supply Chain