falsified medicines directive: irish medicines ... · dr art. 5, 6, 7 dr art. 4 dr art. 8 dr art....
TRANSCRIPT
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: [email protected]
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?