1 Identification and authentication of medicines in Europe: Opportunities and challenges to comply with EU legislation 2017 China/EU Pharmaceutical Industry Forum May 17, Shanghai, China By Mart Levo REKS Estonia The European Medicines Verification Organisation (EMVO) has taken responsibility for advancing the formation of the European Medicines Verifications System (EMVS) in accordance with the EU´s Falsified Medicines Directive (FMD) and Delegated Regulation (DR). In order to achieve the of a functioning, secure, interoperable and cost effective system across Europe, the EMVO pushes for minimum requirements that meet the FMD and the DR for the establishment of a repositories system, i.e. a European Hub with national or supranational verification systems.
2 Introduction: EU-FMD backgroundSafety Features – Impact on Stakeholders EMVO, EMVS and NMVOs Conclusions
3 Recipharm Serialisation Awareness Training23 September 2015 The EU-FMD is good news: 1 common law rather than 32 different laws San Marino Vatican Monaco [One Click Build with zoom animation]: Key message is "the EU-FMD is good news: 1 common law instead of potentially 32 different requirements] The EU-FMD has eliminated the nightmare scenario: 28 different national requirements in Europe: A mix of solutions based on Vignettes, Reimbursement stickers, Security Labels that have to be purchased from the National Mint, national codes carried in different carriers, linear, 2-Dimensional, RFID tags… Instead there is one set of requirements covering the whole of the EU and, in fact, also being adopted beyond, by Switzerland and Norway, for example who are possibly moving faster than some of the member states… ***
4 Countries in scope of the the FMDYellow: 28 EU Member States (MS) Orange: 3 EEA MS (Iceland, Norway, Liechtenstein) Salmon: Switzerland = 32 Countries in scope. ***
5 EU-FMD Timeline 2025 Compliance for MS w. pre-existing measures2014 2015 2016 2017 2018 2019 2020 2011 2012 2013 Compliance for MS w. pre-existing measures 2025 Compliance for MS without pre-existing measures ✓ Publication of Directive in EU Official Journal ✓ Transposition into National Law ✓ Adoption / ✓Publication of Safety Features DA Publication has set the tight 3-year implementation clock ticking for EU-FMD compliance: every pharma company supplying prescription drugs into the European Market will need to be fully EU-FMD compliant by early 2019 [Timeline building up on clicks] “MS (Member States with pre-existing measures” who benefit from the additional 6 years, to give them the 2025 deadline are: Italy, Belgium and Greece. But Belgium have indicated that they will follow the 2019 deadline. ***
6 Key elements of the EU-FMD1) Unique Identifier Fully harmonised across the EU: 2D barcode containing 4 mandatory elements – 1) product code, 2) serialisation number, 3) batch number and 4) expiry date and – optionally – as a 5th element the national reimbursement number (if requested by Member States) 2) Tamper-Evidence Medicinal Products must be tamper-evidenced (EN standard EN 16679:2014 recommended) 3) Repackagers Parallel distributors to replace safety features with equivalent features = UI de/re-commission 4) Scope All prescription medicines (unless white-listed), no OTC medicines (unless blacklisted) 5) Process Systematical end-to-end verification (“before being dispensed to patients e.g. at pharmacy level”) supplemented by risk-based verifications by wholesale distributors: “Medicines at higher risk of falsification (returns or medicines not being distributed directly by manufacturers or marketing authorisation holders or wholesalers distributing on their behalf)” 6) Timing Compliance across all 28 MS (+ 3 EEA) on Publication of DA + 3 years (or + 9 years for BE, GR, IT) 7) Establishment and Operation of the Repository Systems The repository containing the unique identifiers should be set up and managed by stakeholders (stakeholder model) with access and a supervisory role granted to National competent authorities 8) Funding Manufacturers bear the cost of the repository systems [Key elements, revealed on clicks] Directive 2011/62/EC modifying Directive 2001/83/EC and DR 2016/161 Cost: The challenge is how to square the requirements in the legislation with the practical issue of achieving a fair and manageable way of administering the system costs. Linked to that is the agreed approach that the upload of the data to the system will be restricted - for security and performance issues - to one “Manufacturer” = “brand owners” which uploads all the data for its. subsidiaries and CMOs rather than multiple sites or organisational units across many member states. In this context some “manufacturers” = the CMOs should not be required to fund the system but their customers, the brand owners - who hold the Market Authorisations - will be. Key messages, summarised, are: The FMD states that the costs of the repositories system shall be borne by the manufacturing authorisation holders (MFR). The main stakeholders representing manufactures (who are very often also the holders of the marketing authorisations) EFPIA, EGA and EAEPC have agreed upon a model how manufacturers shall pay for the repository systems that is seen to be a transparent, fair, non-discriminatory approach to sharing the cost, proportionate in relation to the services received; this is the flat fee model per marketing authorisation holder (MAH) Where MFR and MAH are the same, this is clearly unproblematic. However, if the MFR and the MAH are not one and the same legal entity, the MAH will be required to pay the flat fee for the use of the system; it is expected that the parties would then agree that the cost can be passed on to the relevant MFR who are legally obliged to bear the cost of the system. ***
7 Unique Identifier Data-Matrix code, developed to ISO-standards Key data elements: Product code (GTIN/NTIN) Batch number Expiry date Randomised unique serial number National health number (where necessary) Serialisation – giving each pack a unique identity – is by comparison a strong authentication feature in it’s own right. It is overt – the serialisation code is visible and can be given semiotic value It is covert – authentic serial numbers are hidden It can be authenticated at distance without losing the value of every serial number It is forensic in the sense that the consumer needs some technology to decode it, however serialisation relies on ubiquitous technology that is already in the hands of consumers telephone networks and the internet But it’s not a silver bullet and may be used in conjunction with conventional authentication features to give the strongest levels of protection for vulnerable products. The key message though is that serialisation is the component of the response that has been, and is being identified by an increasing number of markets as fundamental in their efforts to protect patients from the illegal trade in medicines. The regulatory demands for serialisation are growing and the failure to meet these demands will be a barrier to entry to those markets. The is good news however in that an added bonus of serialisation is that there are wider benefits of the technology that are attractive both to brand owners and consumers and have the potential to offset the cost of implementing serialisation and even generate ROI. *** Product #: Batch: A1C2E3G4I5 Expiry: S/N: AZRQF 2D DM as data carrier of choice: Compact, Robust, Cost-effective
8 Serial Number (EFPIA Pack Coding Guideline)Serialisation for Dummies - SVM Automatik Event, Silkeborg 27th May 2015 Serial Number (EFPIA Pack Coding Guideline) 1) Unique, Random and High Entropy 2) Maximum length 20 chars (alpha- numeric), string should… only contain either lower case or upper case letters, not a mixture. exclude the following letters: i, j, l, o, q and u. (I J L O Q U) = 30 alphanumeric characters available = 2030 possible serial numbers per Product Code Sparseness = the probability that a valid serial number can be guessed should lower than 1 in 10,000 Serial Numbers key requirements are Uniqueness, Randomness and High Entropy. Taking the guidance published by EFPIA which is based on the GS1-standard, using the maximum length of 20 characters, even excluding a number of characters and other limitations leaves you with plenty of numbers. *** = 1,073,741,824,000,000,000,000,000,000,000,000,000,000 © C Integrity Consulting Ltd.
9 Examples for Anti-Tampering Devices (ATD)Flaps Folding boxes closed with glue: A glue (e. g. hot melt, polyurethane, dispersion or other glues) or a combination of glues is applied to glue and close the flaps of the folding box. Specially constructed folding boxes: The flaps and the body of the folding box are constructed in such a way that the flaps are inserted by the manufacturer to close the folding box. Sealing labels and tapes: A label or tape (e.g. from paper, film or laminate) is applied in order to seal the packaging of medicinal products. Film wrappers: The product container or part of it is wrapped in film ensuring the product is appropriately sealed. The film must be ripped or broken to gain access to the product. Sleeves: The closure or the complete product container is shrunk in a film ensuring the product is appropriately sealed. Display blister pack: The product is sealed into a display blister pack which must be cut or broken to gain access to the product. Breakable or tear-away cap: A breakable or tear-away cap is a plastic or metal cap that has a portion that breaks on opening. Thanks to Dieter Mößner, Carl Edelmann GmbH
10 Europe-wide scope of EU-FMD “Safety Features”Safety Features consist of 2 elements: Unique Identifier Tamper Evidence All Prescription Medicines (Rx) are in scope…. …apart from those on the Whitelist Currently white-listed: Radionuclides medicinal gases IV solutions in ATC therapeutic subgroup B05B ‘blood substitutes and perfusion solutions’ contrast media homeopathic medicinal products Over the Counter Medicines (OTC) are out of scope… ...apart from those on the Blacklist Currently black-listed: 2 strengths of Omeprazol Rx Must carry the safety features OTC Must Not carry the safety features [Slide building on clicks]
11 Approach based on the concept: Systematical “Point of dispense verification”
12 Repositories Systems to carry out the Systematical Point of Dispense VerificationNational System National Blueprint System National System European Hub Pharmaceutical Manufacturer Parallel Distributor National System [Note one build on click to change National Systems > National Blueprint Systems"] The purpose of the Blueprint Approach is to minimize overall system costs and the risk to fail. At the same time it supports national stakeholders in implementing their National Medicines Verification System (NMVS) in the easiest way. The most important elements of the Blueprint Approach are: National Systems are implemented and operated based on a “Blueprint standard” as defined in the template of national Memorandum of Understanding the template statutes of an NMVO The EMVO User Requirement specifications (URS) Requirements for the European Medicines Verification System (URS light), including the cost allocation model which set out the rules how Marketing Authorisation Holders and Parallel distributors will be invoiced for using the system. System operation is carried out by pre-qualified IT service providers EMVO offers support to national stakeholders during the system deployment phase Management of National System operation can be partly outsourced to the EMVO to use synergies and for reducing management cost. This Blueprint Approach will give national stakeholders the opportunity to bring into use a pre-designed system according to the agreed principles of the EU stakeholders with a possibility to extend the system functionality due to specific national requirements where necessary (deviations from the blueprint can lead to increased service fees). Pharmacy Wholesaler
13 Introduction: EU-FMD backgroundSafety Features – Impact on Stakeholders EMVO, EMVS and NMVOs Conclusion
14 The Blueprint approach provides substantial benefitNational Blueprint System Complexity reduction for NMVOs: Allows national stakeholders to build national system without starting from scratch = saves time and money Based on a “standard” national verification system providing all necessary functionality = will comply with DR Strong support by EMVO during deployment (quality management) & operation (system management) Cost reduction for payers through economy of scale Several countries buying from the same supplier Coordinated operation Benchmark for Total Cost of Ownership available
15 Stakeholder Impact ManufacturersRequirement (routine operation) Pharma - Brand Owner and Generics Pharma - CMO Parallel Distributors Wholesaler/Distributor Pharmacist National Competent Authorities 1) Pay for EMVS (“Bearing the costs for the system”) Yes no - Marketing Authorisation Holders pay 2) Apply Unique Identifier Yes (requested by customer) 3) Apply Anti-Tampering Device 4) Connect to European Hub: Upload UIs no - will be done by customer 5) Connect to EMVS to Decommission UIs For "consumed" packs (Hub) For packs exported from Europe (National System) 6) Connect to NMVS: Verify UIs for higher risk shipments voluntary check is possible 7) Dispense UIs "Early dispense" for institutions Yes: Point-of-Dispense 8) Process Alerts Where relevant 9) Receive Reports to allow Overview/Supervision [Click to build the slides by revealing additional impact on additional stakeholders] "How are the different stakeholders impacted by the EU-FMD"? Note: Verify = check if UI exists without status change Dispense = Decommission UI at the dispense transaction ***
16 Introduction: EU-FMD backgroundSafety Features – Impact on Stakeholders EMVO, EMVS and NMVOs Conclusion
17 EMVO Mission “The European Medicines Verification Organisation (EMVO) has taken responsibility for advancing the creation of the European Medicines Verification System (EMVS), for the purpose of medicine verification and the enhancement of patient safety, in accordance with the Falsified Medicines Directive (FMD) and the Delegated Regulation (DR), detailing the characteristics of the safety features.”
18 EU-FMD and EMVS Timeline2014 2015 2016 2017 2018 2019 2011 2012 2013 July 1, 2011 Publication of directive in official journal of EU January 2, 2013 Transposition of directive to MS national law February 9, 2016 Publication of Safety F. DR February 9, 2019 Compliance date in 25 EU MS + 3 EEA + CH Connect approx manufacturers to the EU Hub Establish National Systems for 32 countries Connect many thousand Pharmacies and Wholesalers Serialise all pharmaceutical packages in scope (10.5 bn) 2009/2010 Sweden Pharmacy Pilot 2012/2013 EMVS System design Q1 2013 European Hub Provider selected Q1 2014 Link Hub SecurPha rm 2015 Appointm ent of 3 Blueprint Providers EMVS opera- tional EU+ -wide Q4 2011 MoU between EFPIA, PGEU, GIRP signed Q4 2012 MoU with additional stakeholders signed February EMVO stakeholder organisation established March Bulgarian NMVO (1st outside Germany)
19 NMVO and NMVS operational – in “Business As Usual” (BAU)Establishing an NMVO and an NMVS – 2 parallel Workstreams, 4 main steps per workstream Governance Workstream: NMVO and NMVS operational – in “Business As Usual” (BAU) Organisation established IT service up and running SOPs defined Users on-boarded Revenue being collected Alignment between stakeholders NMVO Statutes agreed Memorandum of Understanding NMOV established Technical Workstream: IT service provider selected Project Manager appointed Contract with IT service provider signed Contact to IT service providers established
20 Quality Management The set-up and operation of the NMVS is a core obligation of the NMVOs and will required a solid approach to Quality Management, both during initial set-up and then ongoing operations of the system to achieve the following deliverables: EMVO will offer QA services to support the NMVOs in their QA obligation and provide tools, templates and training. Set-up phase Operational phase Implementation of the NMVO’s QMS Document Management System Software Validation of the NMVS Key Processes to support Daily Operations The system should at least cover the following aspects: Quality Policy Document Management Process Information Security Management Process Change Management Process Incident Management Process Access Management Process Test Management Process Release and Deployment Management Process Roles and responsibilities Training Process
21 7 Constituencies of a NMVO entitled to full membershipSigned up to agreed Governance Principles: Representative: Constituency Approach Fair: 7 Constituencies reperesented Equal: All members have one vote Compliant: Rights & obligations as required by DR Balanced: Veto rights protecting core interests Shared Principles: Data ownership/access; Blueprint & Flat Fee approach Transparent & Trust Building: Continued communication/cooperation with supervising competent authorities & other stakeholders 2) Generic Industry 4) Parallel Distribu-tors 3) OTC Manufacturers 1) Research based Industry 6) Hospital Pharmacies 7) Community Pharmacies Manufacturing Distribution Point of Dispense 5) Wholesalers Associations of Manufacturers, Marketing Authorisation Holders, Wholesalers and Pharmacists should actively take part in all decisions National Stakeholders aim for a fair and balanced division in the voting rights Decisions should be taken on a consensus basis All associations should actively take part in all decisions European Medicines Verification System
22 It is the obligation of the Pharma Industry to establish the repositories systemThe repositories system shall be set up and managed by a non-profit legal entity (NMVO) established in the Union by manufacturers and marketing authorisation holders of medicines in scope = those who must pay for the system Wholesalers, persons entitled to supply medicinal products to the public and relevant national authorities shall be consulted and are entitled to participate in the legal entity on a voluntary basis free of cost (stated in the DR) The statutes for the NMVO can state different membership levels and voting rights The EMVO principle is “pay to vote”, i.e. stakeholders wanting to be Full Members should pay part of the NMVO admin cost
23 How charging works (examples, not real figures)KDH Pharmaceuticals € 81,000 231 Products € 15,000 52 Products ABC Pharmaceuticals € 60,000 6 Products € 18,000 45 Products 34 Products 34 Products € 19,000 25 Products 41 Products 2 Products € 12,000 1 Products € 9,000 1 Products 2 Products 1 Product € 5,000 € 14,000 Tiny Pharmaceuticals € 9,000 1 Product € 19,000 € 14,000 € 12,000 € 19,000
24 Executive Summary Country Readiness April 201715 14 2 20 31 1 18 10 16 24 6 27 13 28 4 3 26 19 17 8 12 30 9 32 25 29 22 7 11 5 23 21 Early Adopter Main Stream Late Follower No Information Non EU Countries
25 Introduction: EU-FMD backgroundSafety Features – Impact on Stakeholders EMVO, EMVS and NMVOs Conclusion
26 The key elements of the EU-FMDSerialization by manufacturer Risk based verification by Wholesalers Verification and check-out at point of dispense Safety features: UI = Code (‘unique identifier’) + ATD = Anti-Tampering Device Product #: Batch: A1C2E3G4I5 Expiry: S/N: AZRQF Manufacturers shall bear the cost of the repositories system EMVO / NMVOs set up and operated by supply chain stakeholders Oversight by competent authorities
27 All stakeholders need to play their role in the Europe-wide systems and processesWholesaler Pharmacy Wholesaler National System National System Pharmacy European Hub Parallel Distributor Brand Owner Obligations: Ensure all Medicinal Products carry SF Report UIs to EMVS via European Hub Process Exceptions and Alerts > Require a capable L4 Repository/EPCIS MAH = Marketing Authorisation Holder = Brand Owner But in parallel MFR readiness must be established. The lessons from early adopters is that this is a major challenge taking a lot of time and effort. The sooner manufacturers start, the better. Don’t forget: If you are not ready by February 2019, you can no longer supply the European Markte! *** Pharmacy Wholesaler
28 Mart Levo Mart [email protected]Thank you very much Mart Levo Mart
29 Glossary BP - Blueprint System DR - Delegated RegulationEMVO - European Medicines Verification Organisation EMVS - European Medicines Verification System FMD - Falsified Medicines Directive MOU - Memorandum of Understanding NBPS - National Blueprint System NMVO - National Medicines Verification Organisation NMVS - National Medicines Verification System