Falsified Medicines Directive: Irish Medicines Verification Organisation (IMVO) update for HPRA GMP Conference LEONIE CLARKE - 7 TH FEBRUARY 2017

Transcription

1 Falsified Medicines Directive: Irish Medicines Verification Organisation (IMVO) update for HPRA GMP Conference LEONIE CLARKE - 7 TH FEBRUARY 2017

2 Safety Features Falsified Medicines Directive(2011/62/EU) requires safety features on most medicines packs to enable relevant persons to identify individual packs and verify their authenticity, i.e. 1. Unique identifiers on each pack 2. Anti-tamper device on outer packaging Commission Delegated Regulation (EU) 2016/161 sets out detailed requirements for unique identifiers, including the repository system where they will be stored New requirements will apply to in-scope medicines released to the EU market from 9 th February 2019

3 Unique Identifiers How will process work? Unique identifiers for products placed on market are stored in a national repository for that market EU Hub links all national repositories and facilitates cross border trade and joint/multimarket packs EU Hub & repository systems are cloud based and data is transferred via Internet Manufacturers upload up unique identifiers into system via EU Hub for transmission to relevant national repositories Wholesaler & pharmacy software systems are adapted to interface with repository Pharmacists scan 2D barcode at point of dispensing and unique identifiers are verified against information in repository & decommissioned Wholesalers also verify and/or decommission unique identifiers in certain circumstances Alert is generated if data in barcode differs to that in repository or is missing See graphic on next slide

4 Unique Identifiers How will process work? Pharmaceutical Manufacturer Product Flow Wholesaler Wholesaler Pharmacist Patient Generates Unique Identifiers Verification / decommissioning as required Verification & decommissioning when dispensing to patient & an alert if any problems Upload to European Hub National Medicines Repository Authenticate Number

5 EU requirements for repositories of unique identifiers* Must be set up & managed by non-profit entity established by MA holders and manufacturers of products with safety features In setting up, must consult at least wholesalers, persons authorised/entitled to supply medicines to public (pharmacists) & national competent authority Wholesalers & pharmacists entitled to participate in legal entity on voluntary basis at no cost Nobody shall be required to be a member of a specific organisation to use the repository system Cost of repository system to borne by manufacturers Every MS must be served by one national or supranational repository based in EU Repositories system does not include scanners needed to read unique identifier * Commission Delegated Regulation (EU) 2016/161 Chapter VII

6 European Medicines Verification System Research based industry Community pharmacists European Medicines Verification System (EMVS) comprises European Hub and national / regional repositories of unique identifiers in each Member State Wholesalers Parallel Distributors Generics industry Collaboration to oversee implementation of unique identifier requirements across Europe Set up as a stakeholder-governed model comprising industry, pharmacists and wholesalers Overseen at European level by European Medicines Verification Organisation (EMVO)

7 High Level Overview of EMVS National System National System National System National System Pharmaceutical Manufacturer European Hub Parallel Distributor Pharmacy National System Wholesaler National System

8 Interface Man. Interf. Paral. Distr. Interf. More Detailed Overview of EMVS Landscape Manufacturer System European Hub Interface Parallel Distributor System System owner = Manufacturer System owner = NMVO Nat Syst. Interf. Interface System owner = EMVO Nat. Blue Pr. Interf. Nat. Blueprint. Interf. System owner = Parallel Distributor System owner = NMVO National Standalone System National System based on blueprint standard Pharmacy Wholesaler Pharm. Interf. Wholes. Interf. Interface Interface Interface Interface Pharmacy System Wholesaler System Pharmacy System Wholesaler System System owner = Pharmacist System owner = Wholesaler System owner = Pharmacist System owner = Wholesaler

9 IMVO s role Role: To set up and manage repository of unique identifiers for Ireland To interface with European Medicines Verification Organisation (EMVO) to ensure full interconnectivity of national repository with European Hub To verify credentials of system users in Ireland To levy fees on manufacturers who use system to cover costs of national repository and Ireland s share of the European Hub costs Irish national repository will be part of EVMS Will operate as independent legal entity (company limited by guarantee)

10 Who s involved in IMVO? Stakeholder organisations involved in IMVO: Research industry Irish Pharmaceutical Healthcare Association (IPHA)* Generic medicines industry Irish Generic Medicines Association (IGMA) and Healthcare Enterprise Alliance (HEA) Pharmaceutical parallel distributors Association of Irish Pharmaceutical Parallel Distributors (AIPPD) Pharmacists Irish Pharmacy Union (IPU) (community pharmacists) and Hospital Pharmacists Association of Ireland (HPAI) Wholesalers Pharmaceutical Distributors Federation (PDF) * BioPharmaChem Ireland (BPCI) also attending meetings

11 IMVO activities to date Memorandum of understanding agreed between stakeholders in March 2016 Work on incorporation as a company limited by guarantee almost complete Communications Engagement with wider industry stakeholders (manufacturers, wholesalers & MA holders) External communications HPRA, HSE, Dept of Health, PSI etc. Formal public consultation July-August 2016 Have mapped national users/stakeholders & work practices to identify any Irish specific requirements (none) Early decision to go with Blueprint approach have identified a preferred bidder (name to be announced when contract is finalised)

12 IMVO activities Selected provider to start developing national repository in Q IT project manager will be appointed to work with selected provider Onboarding of all IT software suppliers, wholesalers and pharmacists in Q Pilot testing to begin in Q will run for several months Systems to be developed to support national repository including: Quality management system Procedures for validating system users and granting access credentials Protocols for managing events that indicate possible incidents of falsification Agree what elements of management of system will be outsourced to EMVO Decision on funding & allocation of users

13 Funding Two elements of cost in IMVO: Governance/running costs of the organisation Costs of repository system i.e. national repository costs & IE share of EU Hub costs Will be funded by memberships subscriptions and by annual user fees charged to all manufacturers/ma holders of medicinal placing products bearing safety features on Irish market NB - pharmacists and wholesalers will not pay for repository system costs (as per DR) Cost allocation model for user fees to be agreed (EMVO advocating flat fee per MA holder) Manufacturer stakeholders in IMVO will cover initial set-up costs and these will then be recouped from all manufacturers/mahs

14 Your role as a manufacturer Need to manage this as an enterprise-wide project, not just manufacturing and IT Critical to be ready well ahead of Feb 2019 deadline High level tasks: Finalise packaging artwork and submit for approval by HPRA Onboard to EU Hub Manufacture serialised packs for Irish market Ensure that unique identifiers for these packs are uploaded to EU Hub IMVO pilot requires reasonable no. of serialised packs available in participating wholesalers and pharmacies from Q & manufacturers key to this IMVO will run information events for MA holders/manufacturers in Q1/Q2

15 Onboarding to EU Hub Approx 2,500 manufacturers ( onboarding partners / OBP )will be linked to EU Hub when system is fully operational Max 2 connections per pharmaceutical corporation/obp Manufacturers must liaise directly with EMVO to onboard to EU Hub, IMVO not involved at all Allow several weeks for this process as there are many stages involved: signing participation and non-disclosure agreements connecting to the system (directly or via a gateway ) uploading data testing (self-certification) going live

16 Onboarding Process Managed and administered by the EMVO s Commercial and Partnership Management Team Managed by the EMVO s Operations Team & Solidsoft Reply 1) Participation Request 2) Legitimacy Check 3) Contractual/ Commercial On-boarding 4) Technical On-boarding Initial Contact Portal registration Non-Disclosure Agreement Level 1 checks Person checks (more detailed checks if necessary) Onboarding Fee payment Connection Request Participation Agreement System Connection System Testing System Operation

17 Relationship between OBP & IMVO OBP EMVO Client EU Hub Collects data from and for Marketing Authorisation Holders (MAH) MAH A MAH B MAH C Production 1 Production 2 Production 3 (CMO) * Onboarding Partner

18 Direct Connection Connection Types EU Hub Gateway Connection 3 Gateway Connection 2 Gateway Connection 1 Gateway Provider X Gateway Provider Y Gateway Connection 3 Gateway Connection 2 Gateway Connection 1 OBP A OBP B OBP C Client a Client b Client c Client d

19 EU Hub Environments ITE IQE PRD ITE environment Integrated Test Environment Used as Sandbox by OBPs Integration testing of OBP s connection IQE environment Integrated Quality Environment Used for Quality & certification testing by OBPs Validated environment PRD environment Productive Environment Validated environment

20 For more information on onboarding to EU Hub Visit EMVO website

21 Quality aspects of implementation: practical guidance from EFPIA EFPIA Supply Chain sub-team has drawn up slides on quality aspects of coding & serialisation following the code end to end see next 3 slides

22 Ref Points to consider Data flow Process Step Quality aspects of coding & serialisation - following the code end to end Assumptions: Codes are printed online, there s no aggregation Master Data & Artwork management Process Order Created Start-up of packing line Pack Produced In Lot re-packing Verify correct master data available Create randomised number series Download data elements to the line Verify 2D barcode and human readable text Commission (associate pack & serial number) Decommission serial numbers Apply new serial numbers Defined and appropriate areas for the required print Consider space needed for multi-market packs. Consider pre-printed HRI* for GTIN**, NHRN*** and prefixes Blue box for centrally authorized products (multimarket packs - one or more codes?) Ensure sufficient amount of numbers available at line including additional quantity for rejects Interface to CMO (eg. send number series or CMO creates serial numbers ) Check code and HRI print quality, content and readability before start up Ensure IPC* include coding & serialisation aspects Include information other than the unique identifier in the 2D barcode, eg. 6 th data element per Art % check or IPC of 2D code quality, content & readability 100% OCR* or IPC presence control for HRI text and print quality Note: A portable scanner or mobile workstation might be an option to be able to remove the part to be repacked from the lot 2 2 * HRI = Human Readable Information ** GTIN = Global Trade Item Number *** NHRN = National Healthcare Reimbursement Number * CMO = Contract Manufacturing Organization * IPC = In Process Controls * OCR =Optical Character Recognition DR Art. 5, 6, 7 DR Art. 4 DR Art. 8 DR Art. 5, 6, 14 DR Art. 16, 17 Directive 2001/83/EC Article 47a

23 Ref Points to consider Data flow Process Step Quality aspects of coding & serialisation - following the code end to end Assumptions: Codes are printed online, there s no aggregation Order Complete Quality Released Quality Certified Picked, packed, shipped and free samples 2 3 Upload serial numbers from packing line to company database Reconcile codes, report as part of batch record Ensure at least as many codes as packs Establish a threshold for the positive difference with justification based on capability and trends QA check or IPC if this has been taken place properly, e.g. data consistency and integrity and manage any deviations QA review & release Batch document check. Print quality ok? Reconciliation ok? Tamper evidence ok? Production order serial number data set uploaded to company database? Any damages or in-lot re-work must include actions for code / data handling EudraLex Volume 4, EU GMP Guidelines Annex 16: Certification by a Qualified Person and Batch Release of 12 October 2015 QP certification Data upload to EU Hub* Confirmation of data upload to EU / national Hub Define who is responsible for upload *Article 33, 1 st paragraph states the information is uploaded in the repositories system before the medicinal product is released for sale or distribution. Note: The optimal point of data upload might be later in the process to avoid different processes for aggregated and non aggregated goods Decommission codes for special reasons Free Samples per Art. 41 Goods for special customers per Art. 23 Export: EU labelled goods for non-eu markets (Packing orders originally intended for non-eu markets do not need upload of codes) per Art. 12 Investigational products intended for clinical trials per Art. 16 Note: Any repacking activity after Quality certification must still comply with the regulation (keep or replace code) Art 33.1 states that the person responsible for placing medicinal products on the market shall ensure that the repositories is kept up to date thereafter DR Art. 33, 38 DR Art. 10, 11, 12, 16, 19, 20, 21, 22, 23, 33, 41 Where a manufacturer distributes his products by wholesale, Article 20(a), and Articles 22, 23 and 24 shall apply to him in addition to Articles 14 to 18.

24 Ref Points to consider Data flow Process Step Quality aspects of coding & serialisation - following the code end to end Assumptions: Codes are printed online, there s no aggregation Recalled, withdrawn or stolen product Returned product Destroyed product General points to consider Ensure decommissioning of unique identifiers Verify authenticity and integrity Verify authenticity of and decommission code Any damages or sampling post QA release must include actions for code / data handling At end of shelf-life system will automatically change status to unavailable Ensure harmonization of common data elements for IDMP and EMVS look for efficiency opportunities Ensure decommissioning of the unique identifier of recalled / withdrawn product Ensure decommissioning of unique identifier of recalled / withdrawn / stolen product where known (not always the case) Note: Suggested principle is that the supply chain actor that initiate an action ensures updates to the hub Authenticity must be verified by checking the serial number status against the EU HUB Products which cannot be reverted to an active status shall not be returned to saleable stock For products intended for destruction authenticity must be verified and the UI* must be decommissioned Ensure harmonization of prefixes / expiry date format (per GS1 standard YYMMDD) Reconciliation and reporting requirements are unclear (at which point in the process?) Impact of alerts / flags from the EU hub and any enquiries from data transactions Handling of customer complaints e.g. from pharmacies if issues with reading of codes 2 4 In case of tampering or suspected falsification immediately inform the relevant competent authorities DR Art. 18, 40 DR Art. 20, 22(b) * UI = Unique Identifier DR Art. 12, 22(c), 40 Handling of customer complaints e.g. from pharmacies if issues with tampering Timelines for transition from linear bar codes (OK with different product identifiers during transition?) Ensure that the information is uploaded to the repositories system before the medicinal product is released for sale or distribution by the manufacturer (see comment on previous slide), and that it is kept up to date thereafter

25 Miscellaneous Department of Health has confirmed that reimbursement codes will not have to be included in the unique identifiers on packs in Ireland EMVS does not currently facilitate the use of aggregated codes

26 Questions?