Falsified Medicines Directive:

Irish Medicines Verification

Organisation (IMVO) update for HPRA

GMP Conference LEONIE CLARKE - 7TH FEBRUARY 2017

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 9th February 2019

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/multi-market 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

Unique Identifiers – How will process

work?

Verification &

decommissioning

when dispensing

to patient & an

alert if any

problems

PatientPharmaceutical

Manufacturer

Generates Unique

Identifiers

Upload to

European Hub

NationalMedicinesRepository

PharmacistWholesaler

ProductFlow

Wholesaler

Verification /

decommissioning

as required

Authenticate Number

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

European Medicines Verification System

European Medicines Verification System (EMVS) comprises European Hub and national / regional repositories of unique identifiers in each Member State

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)

Research

based

industry

Community

pharmacists

Generics

industry

Wholesalers

Parallel

Distributors

High Level Overview of EMVS

NationalSystem

Pharmacy Wholesaler

Pharmaceutical

ManufacturerParallel

Distributor

National

System

National

System

National

System

National

System

National

System

European

Hub

Pharmacy

System

Wholesaler

System

National

Standalone

System

Pharmacy

System

Wholesaler

System

Inte

rfac

e

Pa

ral. D

istr

. In

terf

.

Inte

rfa

ce

Ma

n.

Inte

rf.

Nat Syst. Interf.

Interface

Manufacturer

System

European

Hub

Parallel

Distributor

System

Nat. Blue Pr. Interf.

Wholes. Interf.

Nat. Blueprint. Interf.

Interface

System owner =

Manufacturer

System owner =

Parallel DistributorSystem owner = EMVO

System owner =

NMVO

System owner =

Pharmacist

System owner =

NMVO

More Detailed Overview of EMVS Landscape

System owner =

Pharmacist

System owner =

Wholesaler

National System

based on ‘blueprint

standard’

Pharm. Interf.

Interface

Pharmacy Wholesaler

Interface Interface

System owner =

Wholesaler

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)

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

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)

IMVO activities 2017-2018

Selected provider to start developing national repository in Q1 2017

IT project manager will be appointed to work with selected provider

Onboarding of all IT software suppliers, wholesalers and pharmacists in Q2

2017

Pilot testing to begin in Q3 2017 – 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

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

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 Q2 2017 & manufacturers key to this

IMVO will run information events for MA holders/manufacturers in Q1/Q2

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

1) Participation Request

•Initial Contact

•Portal registration

•Non-Disclosure Agreement

2) Legitimacy Check

•Level 1 checks

•Person checks

•(more detailed checks if necessary)

3) Contractual/ Commercial On-boarding

•Onboarding Fee payment

•Connection Request

•Participation Agreement

4) Technical On-boarding

•System Connection

•System Testing

•System Operation

Managed

and

administered

by the

EMVO’s

Commercial

and

Partnership

Management

Team

Managed by the EMVO’s Operations

Team & Solidsoft

Reply

Onboarding Process

Marketing Authorisation Holders (MAH)

EMVO

EU Hub

OBP

Client

Production 1 Production 2

MAH A MAH B

Production 3 (CMO)

MAH C

Collects datafrom and for

* Onboarding Partner

Relationship between OBP & IMVO

OBP COBP BOBP A

Dir

ec

t C

on

nec

tio

n

Gateway

Provider XGateway

Provider Y

Client a Client b Client c Client d

Ga

tew

ay

Co

nn

ectio

n 2

Ga

tew

ay

Co

nn

ec

tion

3

EU Hub

Ga

tew

ay

Co

nn

ec

tion

1

Ga

tew

ay

Co

nn

ec

tion

2

Ga

tew

ay

Co

nn

ec

tion

3

Ga

tew

ay

Co

nn

ec

tion

1

Connection Types

IQE environment• Integrated Quality

Environment • Used for Quality &

certification testing by OBPs

• Validated environment

PRD environment• Productive

Environment• Validated

environment

ITE IQE PRD

ITE environment• Integrated Test

Environment• Used as ‘Sandbox’

by OBPs • Integration testing of

OBP’s connection

EU Hub Environments

For more information on onboarding to EU Hub

Visit EMVO website https://www.emvo-medicines.eu/

Email: helpdesk@emvo-medicines.eu

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

Quality aspects of coding & serialisation - following the code end to endAssumptions: Codes are printed online, there’s no aggregation

2

2

Pro

ce

ss

Ste

p

Master Data &

Artwork

management

Process Order

Created

Start-up of packing

line

Pack Produced

Da

ta flo

wP

oin

ts t

o c

on

sid

er

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?)

* HRI = Human Readable Information ** GTIN = Global Trade Item Number*** NHRN = National Healthcare Reimbursement Number

Verify correct master data

availableVerify 2D barcode and

human readable text

Commission (associate pack

& serial number)

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…)

* CMO = Contract Manufacturing Organization

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. 6th data element’

per Art. 8

* IPC = In Process Controls

100% check or IPC of 2D code quality, content & readability

100% OCR* or IPC presence control for HRI text and print

quality

* OCR =Optical Character Recognition

Create randomised number

seriesDownload data elements to

the line

In Lot re-packing

Decommission serial numbers

Apply new serial numbers

Note: A portable scanner or mobile workstation might be an option to be able to remove the part to be repacked from the lot

Re

f DR Art. 5, 6, 7 DR Art. 4 DR Art. 8 DR Art. 5, 6, 14 DR Art. 16, 17Directive 2001/83/EC Article 47a

Quality aspects of coding & serialisation - following the code end to endAssumptions: Codes are printed online, there’s no aggregation

2

3

Order Complete Quality Released Quality Certified

Upload serial numbers from

packing line to company

database

Reconcile codes, report as

part of batch record

QA review & release

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

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-workmust include actions for code / data handling

Define who is responsible for upload

*Article 33, 1st 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

QP certification

Data upload to EU Hub*

Confirmation of data upload to

EU / national Hub

Pro

ce

ss

Ste

p

Da

ta flo

wP

oin

ts t

o c

on

sid

er

Picked, packed,

shipped and free

samples

Free Samples per Art. 41 Goods for special customers per Art. 23Export: EU labelled goods for non-EU markets (Packing orders originally intended for non-EU markets do not need upload of codes) per Art. 12Investigational 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”

Decommission codes for special reasons

Re

f EudraLex Volume 4, EU GMP

Guidelines Annex 16: Certification by a

Qualified Person and Batch Release of

12 October 2015

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.

Quality aspects of coding & serialisation - following the code end to endAssumptions: Codes are printed online, there’s no aggregation

2

4

Recalled, withdrawn

or stolen product

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

In case of tampering or suspected

falsification immediately inform the

relevant competent authorities

Ensure decommissioning of

unique identifiers

Pro

ce

ss

Ste

p

Da

ta flo

wP

oin

ts t

o c

on

sid

er

Destroyed productReturned product

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

* UI = Unique Identifier

Verify authenticity of and

decommission code

Verify authenticity and

integrity

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 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

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

General points to consider

Re

f

DR Art. 12, 22(c), 40DR Art. 20, 22(b)DR Art. 18, 40

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

Questions?