Falsified Medicines Directive Info session for MAHs

Falsified Medicines Directive Info session for MAHs 25/4/2017 14u 17u Auditorium at Wolubilis

Agenda Welcome MAH responsibilities in FMD Products to market Q&A Interaction with the Verification system Q&A Management of the Verification system Q&A Closing notes H. Van Eeckhout JP. Engels D. T Jampens J. Janssens P. Boudrez M. Gryseels T. Schmitz MAH Event 25/4/2017 Falsified Medicines Directive 2

MAH Event 25/4/2017 Falsified Medicines Directive 3

Falsified Medicines Directive Legal framework Directive Directive 2011/62/EU published on 1 July 2011 To be detailed via a delegated act; Obligatory safety features on the outer packaging of the medicines, Transposition by Member States into national law Transpose into national law by 2 January 2013. The transposition process is now complete. Implementation of the Falsified Medicines Directive Outlined in EU secondary legislation (Delegated Regulation) Published 09 Feb 2016 Time frame : implementation by 09 Feb 2019. Philosophy : stakeholder model - managed outsourcing by government The pharma sector will initiate, organize and finance the system Via special purpose VZW/ASBL With limited involvement of government MAH Event 25/4/2017 Falsified Medicines Directive 4

Basic concept: Point of dispense verification Mandated by Delegated Regulation MAH Event 25/4/2017 Falsified Medicines Directive 5

Basic concept: Point of dispense verification Each MAH: Adapt packs & production line Each MAH: Interaction with the Verification system MAH stakeholders: Manage the Verification system Mandated by Delegated Regulation MAH Event 25/4/2017 Falsified Medicines Directive 6

Medicines Verification System Manufacturer System System owner = Manufacturer Interface Man. Interf. System owner = EMVO European Hub Nat. Blue Pr. Interf. Paral. Distr. Interf. Interface Parallel Distributor System System owner = Parallel Distributor System owner = BeMVO Nat. Blueprint. Interf. National System based on blueprint standard Pharm. Interf. Interface Wholes. Interf. Interface Pharmacy System Wholesaler System EMVO European Medicines Verification Organization BeMVO Belgian Medicines Verification Organization MAH Event 25/4/2017 Falsified Medicines Directive 7

Tree levels of organisation HUB EMVO VZW / ASBL member: EU stakeholders association Role and Responsibility Building and exploitation of HUB Overall program management Support for scale effects Offices in Brussels Upload of product data BeMVS Verification BeMVO VZW / ASBL 7 constituencies / 8 found. Members (Pharma.be / Febelgen / BAPI / BACHI APB / Ophaco /BVZA-ABPH/ NVGV-ANGR) Role and Responsibility Building and exploitation of National MVS Overall project management Collection of membership fees & contributions BeMVO under construction COMPANY SYSTEMS STAKE- HOLDERS All companies in medicine supply chain MAH + Wholesalers +(Hosp.) Pharmacists Role and Responsibility Apply the FMD regulation Use the MVS system MAH Event 25/4/2017 Falsified Medicines Directive 8

Time to start NOW 2017 2018 2019 1. Project implementation Pre-pilot Pilot Ramp up Validation 2. Products to market Do I have products in Scope? Change my Artwork Submit my Variations Modify my production line Bring products to the market 3. Interaction with the Verification system Get my GTIN codes Connect to the Hub Load and manage my codes My internal processes 4. Manage the Verification system Participate in Pilot phase Contract to National system MAH Event 25/4/2017 Falsified Medicines Directive 9

Time to start NOW 2017 2018 2019 1. Project implementation Pre-pilot Pilot Ramp up Validation 2. Production line Do I have products in Scope? Change my Artwork Submit my Variations Modify my production line Bring products to the market 3. Interaction with the Verification system Get my GTIN codes Connect to the Hub Load and manage my codes My internal processes 4. Manage the Verification system Participate in Pilot phase Contract to National system MAH Event 25/4/2017 Falsified Medicines Directive 10

Bring my products to the market Dany T Jampens

Products to Market Scope of FMD for Belgium (*) With NCA following scope of FMD has been defined Use of the UI All medicinal products subject to prescription Plus Black List Minus White List Plus all reimbursable products in BE bearing a RIZIV/INAMI serial bar code today. Use of the ATD All medicinal products subject to prescription Plus Black List Minus White List Plus all other products on a voluntary basis based on risk assessment submission and agreement of FAGG. 2D Matrix for products out of scope The parties confirm that, for the products out of scope, the use of the 2D Matrix (without a UI) will be on a voluntary basis. For these products still without a 2D Matrix the parties advise to use the CNK. See decision table that will be published on the BeMVO website (*) based on informal agreement with Belgian National Competent Authority MAH Event 25/4/2017 Falsified Medicines Directive 12

Products to Market Impact of FMD on Pharmaceutical Packaging - General The Delegated act (Commission Delegated Regulation 2016/161) imposes the pharmaceutical industry to apply safety features to the medicinal products in scope of the regulation Unique Identifier (UI) Two-dimensional barcode Anti-Tampering Device Why? To allow the verification of the authenticity of medicinal products subject to prescription and protect patients and business alike from the risks of falsified medicines MAH Event 25/4/2017 Falsified Medicines Directive 13

Products to Market Impact of FMD on Pharmaceutical Packaging Unique Identifier Technical specifications: sequence of numeric or alphanumeric characters unique to a given pack of a medicinal product shall consist of the following data elements: a code allowing the identification of at least the name, the common name, the pharmaceutical form, the strength, the pack size and the pack type of the medicinal product bearing the unique identifier ( product code ) a numeric or alphanumeric sequence of maximum 20 characters, generated by a deterministic or a non-deterministic randomisation algorithm ( serial number ) the batch number the expiry date The probability that the serial number can be guessed shall be negligible and in any case lower than one in ten thousand. The character sequence resulting from the combination of the product code and the serial number shall be unique to a given pack of a medicinal product until at least one year after the expiry date of the pack or five years after the pack has been released for sale or distribution whichever is the longer period. MAH Event 25/4/2017 Falsified Medicines Directive 14

Products to Market Impact of FMD on Pharmaceutical Packaging UI Two-Dimensional Barcode Barcode shall be a machine-readable Data Matrix (further: 2D matrix) Carrier of the unique identifier Technical specifications for 2D matrix are presented in Delegated Act Quality of printing of 2D matrix to be verified by manufacturers MAH Event 25/4/2017 Falsified Medicines Directive 15

Products to Market Impact of FMD on Pharmaceutical Packaging UI - Human Readable Form Content of 2D matrix must also be present in human readable format Product code Serial number Not required when sum of two longest dimensions of packaging 10cm (e.g., eye drops) When human readable required, should be adjacent to 2D matrix Always required Product Code Serial Number Only required on boxes > 10cm MAH Event 25/4/2017 Falsified Medicines Directive 16

Products to Market Impact of FMD on Pharmaceutical Packaging Anti-Tampering Device No specific requirements Manufacturer s choice which ATD to use Labeling (with or without perforation) Hot-Melt Gluing with perforation Self-destroying folding boxes Wrapping MAH Event 25/4/2017 Falsified Medicines Directive 17

Products to Market Impact of FMD on Pharmaceutical Packaging - Conclusion For all products in scope of FMD, the lay-out of the secondary packaging is about to change: Add anti-tampering device Add 2D matrix Add Product Code and Serial Number Remove linear sequential barcode MAH Event 25/4/2017 Falsified Medicines Directive 18

Products to Market Post-FMD Secondary Packaging Big Boxes All Data Printed On-line MAH Event 25/4/2017 Falsified Medicines Directive 19

Products to Market Post-FMD Secondary Packaging Big Boxes Reduced On-line Data Printing MAH Event 25/4/2017 Falsified Medicines Directive 20

Products to Market Post-FMD Secondary Packaging Big Boxes Too Large for Exemption, but too Small for Grouping Box too big for exemption (> 10cm), but too small to fit all the human readable version of variable text on one panel There is no obligation to place LOT and EXP adjacent to the 2D matrix The 2D matrix, PC and SN can be printed on one panel, LOT and EXP on another panel MAH Event 25/4/2017 Falsified Medicines Directive 21

Products to Market Post-FMD Secondary Packaging Small Boxes Only 2D matrix Human readable version of PC and SN not mandatory may if possible LOT & EXP required, as before MAH Event 25/4/2017 Falsified Medicines Directive 22

Products to Market Post-FMD Secondary Packaging CNK In-Scope Products MAH Event 25/4/2017 Falsified Medicines Directive 23

Products to Market Post-FMD Secondary Packaging CNK Out-Of- Scope Products For products not subject to FMD, CNK code still to be used on the folding box Industry associations recommend however to evolve from CNK code to 2D matrix also for products out of scope (for harmonization in market) Content of this 2D matrix will then be: PC Lot EXP No SN is allowed for exempted products! MAH Event 25/4/2017 Falsified Medicines Directive 24

Products to Market Regulatory Variations - Current Requirements for Packaging Changes Based on circular letter 423 (24-FEB-2003) the FAMHP requests that companies are submitting the product information as per QRD template Version 10 of QRD has been updated to include provisions for the implementation of the Falsified Medicines Directive. Following sections have been added: Section 17, UNIQUE IDENTIFIER 2D BARCODE Section 18, UNIQUE IDENTIFIER - HUMAN READABLE DATA Product Code to be identified with: PC (NL/FR/DE) Serial Number to be identified with: SN (NL/FR/DE) MAH Event 25/4/2017 Falsified Medicines Directive 25

Products to Market FMD Related Regulatory Variations How to submit? Combine with any variation that is to be submitted for concerned products or via Art. 34 4 notification Implementation period not limited to 6 months (due: Feb 9, 2019)! (1,2) Submit one variation for implementation of FMD requirements, even when there s a stepwise approach, e.g., Step 1: Add 2D matrix Step 2: add anti-tampering device Step 3: reduce blue box size (as serial barcode no longer needed) Grouping and cost of variations In discussion with FAGG Decisions to be validated by Transparency Commission (1) EMA - http://www.ema.europa.eu/docs/en_gb/document_library/other/2016/02/wc500201413.pdf (2) CMDh - http://www.hma.eu/fileadmin/dateien/human_medicines/cmd_h_/falsified_medicines/cmdh_345_2016_rev00_02_2016_1.pdf MAH Event 25/4/2017 Falsified Medicines Directive 26

Products to Market Regulatory Variations Mock-Up Needed? Impact Mock-Up Declaration Not Significant (1) NO Declaration of no significant impact on mock-up Significant (2) YES N/A (1) 2D matrix replaces CNK and no other changes to packaging (2) Impact on readability of packaging MAH Event 25/4/2017 Falsified Medicines Directive 27

Products to Market Pack design Important Timelines (*) Tree pack situations are possible for your convenience 1. Packs with only old serial bar code system Possible to bring old serial bar code packs on market till 08 FEB 2019 2. Packs with old serial bar code and new 2D matrix in parallel During transition it will be possible to bring packs on the market with both old and new code on packs Possible as from today till 09 FEB 2019 Instructions regarding pack design and variations : see 3. Packs with only new 2D matrix Packs with only 2D matrix are possible as from AUG 2018 To facilitate transition especially for smaller packs with no possibility to have both codes systems on pack For this to happen : all pharmacies and Riziv must agree and be ready to work with 2D matrix system! 4. Same rules apply to Prescription Bound & Not Reimbursed products (*) based on current views and instructions of EMVO and informal agreement with FAGG and Riziv MAH Event 25/4/2017 Falsified Medicines Directive 28

Products to Market Start Preparing... NOW! Artwork Analyze your artwork components Shared packs amongst countries same country requirements? If not: country specific packs? impact on supply chain (MOQ)? Space for 2D matrix, anti-tampering device? Develop a strategy for artwork changes Capacity, lead times, etc. Resources & budget!!! Anti-Tampering Device Define your standard (one or multiple) Identify supplier Testing of solution on boxes (e.g., stability study for label adhesion on boxes / compatibility with varnish) Patient testing MAH Event 25/4/2017 Falsified Medicines Directive 29

Products to Market Start Preparing... NOW! Production Printing of or labeling with 2D matrix, PC and SN Printing: Adapt and validate packaging lines (technical, IPC checks, data integrity) Random serial number generator needed Labeling: Which printing company can supply labels with 2D matrix, PC and SN? Data integrity throughout supply chain (how to protect serial number information) Adapt for anti-tampering device Handling of serial numbers from generation to upload in EU hub Working with contract manufacturing? Rework / Repackaging How to change leaflets in tamper-evident boxes? Release process QA/QP oversight to be defined Return process How to handle returned units? How to check whether decomissioned or not? Quality System How to operate in serialized environment? Cost-Of-Goods? MAH Event 25/4/2017 Falsified Medicines Directive 30

Q & A MAH Event 25/4/2017 Falsified Medicines Directive 31

Managing the product codes Jan Janssens

Connect to System GS1: Non Profit Setting Global Standards GS1 sets Standards for identification of in collaboration with business: Products: Global Trade Identification Numbers (GTIN) Company/Location: Global Location Number (GLN) Assets: Global Individual Asset Identifier (GIAI) Global Returnable Asset Identifier (GRAI) Logistics: : Serial Shipping Container Codes (SSCC) Standards in data Carriers & Barcodes: Data matrix, EAN, ITF, Standards in data exchange (EDI) MAH Event 25/4/2017 Falsified Medicines Directive 34

Connect to System CNK replaced by GTIN 13/14 Belgian decision Elements of GTIN 14: Country of GS1 membership(belgilux): 54 Company Prefix: length defining number of products possible and cost Article Number: 2 to 5 digits for Belgium->#codes 100 to 100000 Check Digit: check correct read out of product Indicator: identification level: e.g. tablet, blister, sales pack, bundle, carton, => ALLOCATION RULES FOR STATIC DATA SET: www.gs1.org/docs/gsmp/healthcare/gs1_healthcare_gtin_allocation_rules.pdf A GTIN in healthcare can never be re-used! MAH Event 25/4/2017 Falsified Medicines Directive 35

Connect to System Next step 2D Matrix: Data Matrix ECC 200 version Static data GTIN Dynamic data: Application Identifier (AI) Lot number Expiration date Production date Serial number, AI Code Pharma Data Set Format End indicator 01 PC GTIN 14 N14: 14 Numeric Values 17 Exp Expiry Date N6: 6 Numeric Values 10 Lot Batch N X..20: Up to 20 Alphanumeric Values FNC1 21 SN Serial N X..20Up to 20 Alphanumeric Values FNC1 Barcode Specifics: L-Shaped pattern Checkerboard pattern Error correction X-Dimension = one module Margins: 1 x X-dimension Default Pharma data capacity requirement Content: 24x24 => Impact size and technical requirements! MAH Event 25/4/2017 Falsified Medicines Directive 36

Connect to System Action Points Things to consider: GS1 Membership: Local or Global Approach Number of codes required: Company code length! Coding Database & Allocation Methodology Production: Technical Requirements & checks GTIN to CNK: Set up in discussion with Stakeholders Refunding adjust database RIZIV EDI communication set up MAH Event 25/4/2017 Falsified Medicines Directive 37

Connect to System Hub Processes for the MAH Onboarding process Managed by EMVO https://www.emvo-medicines.eu/eu-hub-on-boarding/ HUB is fully operational and tested - MAH started to upload data (3-6 mnths) Participation request Legitimacy check Contractual onboarding Technical onboarding Training video: https://www.youtube.com/watch?v=of5k7uhfxle&feature=youtu.be FIRST : Check if your corporation is managing the connection with the Hub centrally for you? Yes, Principle of OnBoarding Partner group all MAH to 1 connection No, Start onboarding process with EMVO Organize your internal processes MAH Event 25/4/2017 Falsified Medicines Directive 39

Q & A MAH Event 25/4/2017 Falsified Medicines Directive 40

Manage the System Managing the Verification system Delegated Regulation: the Marketing Authorization Holders are responsible for implementing and managing the Verification system Set up the not-for-profit organization BeMVO Contract the IT Service Provider Implement and roll out the Verification system Assure efficient ongoing operations Successful implementation - Pilot phase Distribution stakeholders MAH Packaging & production line Connect to Hub Load data to Hub Contract BeMVO MAH Event 25/4/2017 Falsified Medicines Directive 42

Manage the System Pilot phase Pilot starts TODAY Because of RIZIV/INAMI readiness by 2018 selected products : Rx products, not-reimbursed MAH evaluating to participate as a Pilot can let this know to the BeMVO latest by 30/5/2017 MAH participating to the pilot will benefit from Strong support (guidelines and procedures) from the BeMVO Accelerated approval procedure at FAGG (if variation only for FMD) Extended technical support from the IT provider Additional information sessions TO DO o Select product(s) to take in Pilot o Artwork, submit variations & get approval o Production line & Bring to market o Connect to Hub and load data to Hub o Contract to BeMVO (*see further) Register NOW as Pilot candidate by mail to info@bemvo.be MAH Event 25/4/2017 Falsified Medicines Directive 43

Financing the BeMVO and BeMVS Pieter Boudrez

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Manage the System Budget criteria by BeMVO Lean and mean organisation Max 2 headcounts staff Quality, reporting, communication, link with IT-provider Low cost structure (offices, multistakeholder ) EMVS contribution Unforeseen expenses possible (quality, EMVS, blueprint deviations ) Buffer needed but will be brought to minimum reserve within first two years of operational BeMVO Discount on yearly flat fee GD Luxembourg will pay their share MAH Event 25/4/2017 Falsified Medicines Directive 46

Manage the System Budget buildup Constituency fees for associations full members One Off Registration fees per MAH Yearly Flat fee per MAH as of february 2019 Contributions of MAH s to be collected MAH Event 25/4/2017 Falsified Medicines Directive 47

Manage the System Criteria Every MAH active in Belgium (on Feb, 9th 2019) has to be contracted Every MAH active in Belgium needs to contribute directly Invoice per MAH Number of MAH s is uncertain and volatile FMD-compliant Rationalisation Auto-check of all MAH s to be in line with BeMVO obligations Check scope FMD Check structure of MAH s within corporate organisation MAH Event 25/4/2017 Falsified Medicines Directive 48

Manage the System Variabilities to manage in the budget Number of MAH s Contracting the MAH s Possible rationalisation Budget to be foreseen in total Risk factors Unforeseen costs Unforeseen changes on European level Payment period by MAH s IT-implementation density MAH Event 25/4/2017 Falsified Medicines Directive 49

Manage the System Registration process Need to register in 1 of 3 waves Added value to register quickly: Ready for testing on national level Ready for testing on European level Time to adjust internal systems and processes Lowers the cost on BeMVO level Check your MAH/corporate position right now MAH Event 25/4/2017 Falsified Medicines Directive 50

Manage the System After registration Phase till 9 february 2019 One off registration fee in 3 waves After 31 may 2018: registration fee of 20000 + admin cost for those already active in Belgium After 9 february 2019 New MAH: one off registration fee of 20000 /MAH Yearly flat fee to be paid per MAH to cover operational costs Amount to be calculated Q4 2018 If substantial reserves on BeMVO-level discount on yearly flat fee for first 2 years will be applied MAH Event 25/4/2017 Falsified Medicines Directive 51

Manage the System Wrap up Action points - registration process Letter of invitation to registration will be sent to all MAH All MAH known by FAGG (name, address, ) Check if your MAH will act within scope of FMD in Belgium on FEB, 9th 2019 Sign up and indicate what wave you prefer to register into BeMVO Lines open as of 2 may via info@bemvo.be Complete, sign the contract and return to BeMVO (email) Template will be provided via website www.bemvo.be and been pushed through umbrella organisations Signature by authorized persons Invoice will be sent to MAH Remember: Auto control responsiblity If no contract and/or no payment received on FEB 9th, 2019 Registration fee at + full rate Potentially No access to FMD Belgium/BeMVO MAH Event 25/4/2017 Falsified Medicines Directive 52

Q & A MAH Event 25/4/2017 Falsified Medicines Directive 53

Key takeaways Overall responsibility of the MAH in the FMD stakeholder model Check if you are concerned by the scope Modify your pack layout and bring new designed packs to the market Connect to the Verification System via the Hub Manages your codes (GTIN and serial number) and reorganize internal processes Participate in the Pilot for a fluent start Take your responsibility towards the management and financing of the Verification System START NOW! MAH Event 25/4/2017 Falsified Medicines Directive 54

Closing Remarks M. Gryseels T. Schmitz MAH Event 25/4/2017 Falsified Medicines Directive 55

Addenda MAH Event 25/4/2017 Falsified Medicines Directive 56

Your To Do s check list 1 General 1. Do I have products if scope of FMD? If one product in scope on Belgian market => be FMD compliant Scope definition : see Addendum slide p59 2. Register yourself and sign contract with BeMVO Make yourself visible towards the BeMVO All MAH should sign contract with BeMVO to access the system Will be the only basis for invoicing of contributions Process : see slide 52 4. Pay your One-Off Registration Fee A first financial contribution is foreseen to cover costs of investment and operations before FEB 2019 Process, timing and fee levels : see slide 49 5. Evaluate opportunity to joint the pilot projects We work with fazed implementation and well defined pilot projects Process, timing, criteria and benefits to participate in pilots : see slide 42 MAH Event 25/4/2017 Falsified Medicines Directive 57

Your To do s check list 2 Your workstreams 1. What is the process of onboarding? All requested information should be uploaded via EU Hub This must be done by you or your OBP Before uploading you need to onboard in the HUB For instructions of onboarding : see slide 38 2. GTIN For Belgian : we will work with GTIN for product identification More information : see slides 33-36 3. Adapted pack design and (cost of) variations Implementation of FMD will require Adaptation the pack design Submission of variations All information about process and design rules :see slides 11-29 4. Impact assessment on your organization Start as soon as possible the impact assessment Potential domains : ICT functions / access management process / warehousing / transport / MAH Event 25/4/2017 Falsified Medicines Directive 58

Scope for FMD in Belgium Rx - product NON Rx - product on white list not on white list not on black list CHARACTERISTICS (8) reimbursable not reimbursable reimbursable not reimbursable reimbursable on black list not reimbursable reimbursable not reimbursable FMD SCOPE case number Compulsory ATD? (0) Compulsory 2D-Matrix with UI? For FMD packs - Should Human readable PC and SN be on pack? Is pack > 10 cm? (3) Is pack < or = 10 cm? (3) Possible to put adjacent (5)? => PC and SN adjacent ==> Obliged to put on pack Not possible to put adjacent (5)? => free to put on wathever place/panel (3) ==> Not obliged to put on pack No obligation but if possible and willing to do => free to put on whatever place/panel Can I put a Can I put a 2D-Matrix liniair code? without UI? FOR non FMD PACKS GTIN OR CNK (6) COMPULSORY ACCORDING TO RIZIV RULES not bearing code today 1 VOL N NA - not in FMD NA - not in FMD NA - not in FMD Y Y COMPULSARY bearing code today (7) 2 VOL N NA - not in FMD NA - not in FMD NA - not in FMD Y Y COMPULSARY not bearing code today 3 VOL N NA - not in FMD NA - not in FMD NA - not in FMD Y Y FREE bearing code today (7) 4 VOL N NA - not in FMD NA - not in FMD NA - not in FMD Y Y FREE not bearing code today 5 Y Y N Y IS AN FMD PACK bearing code today (7) 6 Y Y N Y IS AN FMD PACK not bearing code today 7 Y Y N Y IS AN FMD PACK bearing code today (7) 8 Y Y N Y IS AN FMD PACK not bearing code today 9 Y Y N Y IS AN FMD PACK bearing code today (7) 10 Y Y N Y IS AN FMD PACK not bearing code today 11 Y Y N Y IS AN FMD PACK bearing code today (7) 12 Y Y N Y IS AN FMD PACK not bearing code today 13 VOL N NA - not in FMD NA - not in FMD NA - not in FMD Y Y FREE bearing code today (7) 14 VOL Y N Y IS AN FMD PACK not bearing code today 15 VOL N NA - not in FMD NA - not in FMD NA - not in FMD Y Y FREE bearing code today (7) (8) 16 VOL N NA - not in FMD NA - not in FMD NA - not in FMD Y Y FREE (0) VOL = voluntary (1) N = NO Y=YES (3) Is the sum of the two largest dimensions of the pack >10 cm? (4 )Is the som of the two largest dimension of the pack > or = 10 cm? (5) Adjacent = just above, left, right or under the 2D matrix (6) For non FMD packs recommanded to evolve from CNK code and liniair bar code to GTIN and 2D matrix for harmonisation in the market. => content of 2D martrix will be : PC + LOT +EXP. Remark : SN is NOT allowed out of scope products. (7) Denomination 'bearing code today' will evolve in the futur to 'bearing a public price" (8) Some cases / combinations are be purely theoritical MAH Event 25/4/2017 Falsified Medicines Directive 59