1. Gap analysis between Article 57(2) of EC Regulation and the epSOS eP
Giorgio Cangioli , HL7 International Foundation
Paolo Alcini, European Medicines Agency
Member States authorities and Competence Centres Engagement Workshop.
Luxembourg, 21st April, 2015

2. Table of Contents The context
The epSOS experience..
…what’s happening now… (EXPAND, openMedicine,..)
…the EMA Art. 57 Database
How Art. 57 Db can help the cross-border eP
The epSOS Art. 57 Gap Analysis
Proposed approaches
Conclusions

3. The Context
The epSOS project, its “children” (EXPAND, openMedicine) and the EMA Art. 57 database

4. The epSOS experience
The epSOS project piloted the cross-country exchange of medications information in several use cases:
ePrescription / eDispensation
Patient Summary
Healthcare Encounter Report
Medication Related Overview
Without a common European Drug Nomenclature (like RxNorm in US) drugs have been “identified” in epSOS using a set of attributes (ingredients, strengths, form code, route of administration, …) that describe them

5. The epSOS experience
Those data are conveyed using epSOS defined CDA extensions, based on standard models, relying on commonly available coding systems: ATC (for substances) , EDQM (form code, route of administration, …),…
Several shortages have been however experienced in epSOS:
Capability of providing structured and coded information (particularly for multiactive ingredients products)
Mapping issues with local codes
Concepts in EDQM which countries cannot map nor translate to
Suitability of the ATC code system for the identification of the active ingredients (ATC is not conceived for that)
Management of the “complex” packages
Display of the received information (e.g. non physical units: tablets, puffs,…=> Unit of Presentation)
…….

6. …what’s happening now…
The EXPAND Thematic Network [ ] ( has taken over most of the issues identified in epSOS and some mitigation actions has been agreed for facilitating the prosecution of the pilot, leaving however the most relevant topics to the openMedicine project
The openMedicine Coordination & Support Action ( [ ] aims to
Contribute towards and enhance the safety and continuity of cross-border (and also national level) healthcare through interoperable ePrescriptions
Develop concrete solutions to: “The challenge in ePrescription is how medicines can be communicated in the cross border setting.”

7. Then ? EXPAND provided solutions for short term eP pilots
openMedicine is looking for long term comprehensive answers (based on the ISO IDMP Identification of Medicinal Products standards)
What can be done in the medium term for improving the eP interoperability ?

8. Fundamental questions from epSOS
Can the EMA work, undertaken because of the pharmacovigilance legislation, contribute towards improving interoperability of databases and safety and interoperability of ePrescriptions?
YES
«It – could – work!»

9. How the Art. 57 DB can help the cross-border eP
epSOS vs Art. 57 Gap analysis, Proposed approaches

10. ...the Article 57 Database (governance)
The submission of data on medicines by marketing-authorisation holders is a legal requirement introduced by the Article 57(2) of Regulation (EU) No 1235/2010 (2010 pharmacovigilance legislation)
NCAs & EC grant/ amend
Marketing Authorisations of Medicinal Products following evaluation and approval of product information
15 days from
initial marketing authorisations
30 days from
variation of marketing authorisations
Article 57
Database
Article 57 database contains regulated information on Medicinal Products in Europe

11. …the Article 57 Database (Content)
Structured Medicinal Product Information:
P1: MAH (Legal Entity)
P2: QPPV
P3: PhV Enquiries
P4: PSMF
P5: Authorisation country code
P6: Authorisation procedure
P7: Authorisation status
P8: Authorisation number
P9: Authorisation date
P10: MRP/DCP/EU number
P11: Date of withdrawal/revocation/suspension
P12: Package description
P13: Orphan drug designation
P14: Comments (e.g. paediatric use)
P15: Medicinal product name
P16: Medicinal product invented name
P17: Product generic name
P18: Product company name
P19: Product strength name
P20: Product form name
P21: Pharmaceutical Form
P22: Route of administration(s)
P23: Active ingredient(s), Adjuvant(s)
P24: Excipients
P25: Medical device(s)
P26: Strength of active ingredient(s)/adjuvant(s)
P27: Therapeutic Indication(s)
P28: ATC code
P29: Medicinal Product type/Legal Basis
Unstructured Medicinal Product Information:
P30: Summary of Medicinal Product Characteristics
Substance controlled terminology:
S1: Substance names
S2: Substance Translations
S3: Substance synonyms
S4: Substance class
S5: Reference source
S6: International Codes
Multilanguage
Reference controlled terminology:
R1: Pharmaceutical form
R2: Route of Administration
R3: ATC codes
R4: Units of Measurement (UCUM)
R5: Units of presentation
R6: Reference source
). The following structured information is electronically submitted and therefore available in the XEVMPD:
1. description of the (invented) name of the medicinal product;
2. details of the marketing authorisation holder (including the name, address and a description of the size of the organisation i.e. SMEs);
3. details of the marketing authorisation such as the status and date (e.g. withdrawal, valid); marketing authorisation procedure and legal basis; marketing authorisation country and related authorisation numbers; Orphan drug designation;
4. description of the pharmacodynamic properties based on the ATC code(s) of the medicinal product;
5. description of the therapeutic indications coded in MedDRA and a declaration that the medicinal product is "authorised for the treatment in children";
6. details of the qualitative and quantitative composition of the medicinal product, including the list of active substance(s), adjuvant(s) and excipients, and the strength (amount) of the active substance(s) (and adjuvants where applicable);
7. description of the medical device(s) for combined advanced therapy medicinal products in accordance with Regulation (EC) No 1394/2007 as applicable;
8. the authorised and administrable pharmaceutical form(s);
9. description of the posology and method of administration (i.e. Route(s) of administration);
10. pharmacovigilance information such as the name and contact details of the Qualified Person Responsible for Pharmacovigilance (QPPV), the location of pharmacovigilance system master file, and the organisation contact and phone number for pharmacovigilance enquiries;
11. an electronic copy of the latest approved Summary of Product Characteristics (SmPC) including version date, document reference number(s) and document language(s).
Most of the information available in the XEVMPD is encoded based on a set of controlled terminologies e.g. XEVMPD substance controlled vocabulary, pharmaceutical form(s) and routes of administration(s).
Organisation controlled terminology:
O1: MAH (Legal Entity) details
O2: QPPV
O3: PhV Enquiries
O4: PhV System Master File

12. …the Article 57 Database (Content)
Product Report Repository
Brand name 1
Brand name 2
Brand name 1
XEVPRM Format
XEVPRM Format
Brand name 2
Scientific Product
Repository
Paracetamol 100mg Tablet
Paracetamol 100mg
Paracetamol Tablet
Paracetamol
Abstract composition codes represents the Pharmaceutical Product independently from its commercial form, identified as Non Proprietary Medicinal  Preparation

13. Art. 57 Vs epSOS gap Analysis
The project team performed a gap analysis with the perspective of supporting the epSOS use cases using the EMA “facilities”
Data models comparison
Vocabulary comparison
I.e. is out of the scope of this analysis to consider how the epSOS

14. Art. 57 Vs epSOS gap Analysis
Data Model
Information available in the EMA database is substantially a superset of what is required by epSOS
the only exception concern the type of outer package, coded in epSOS and provided as general description in the EMA DB.
Not a critical issue
I.e. is out of the scope of this analysis to consider how the epSOS

15. Art. 57 Vs epSOS gap Analysis
Vocabulary
The adoption of some XEVMPD (eXtended EudraVigilance Medicinal Product Dictionary) vocabularies may resolve most of the epSOS known issues (e.g. the identification of the active ingredients)
Substance names
Pharmaceutical form
Route of Administration
ATC codes
Units of Measurement
Units of Presentation
I.e. is out of the scope of this analysis to consider how the epSOS

16. Art. 57 Vs epSOS gap Analisys
Main gaps are
Different versions of adopted code system: WHO ATC, EDQM (European Directorate for the Quality of Medicines)
Usage of EMA specific code system extensions (mainly for EDQM) (i.e. pre-adoption of concepts not yet included in the official release)
Different approach on the management of the units of measure, both based on UCUM (Unified Code for Units of Measure)
Notation : case sensitive Vs case insensitive
Adopted Logic : prefix and unit (e.g. ‘m’ and ‘g’ as separate fields) Vs pre-coordinated unit (e.g. mg)
Usage context: specific (strength denominator; strength numerator) Vs broad scope (any field where units are used)
EMA provides suitable vocabularies, currently not foreseen in epSOS (ingredients (non ATC); unit of presentations)

17. Possible approaches
Two possible - not mutually exclusive - approaches have been identified:
Use the ART 57(2) Database for filling the epSOS data structure: i.e. communicate the detailed and complete information on the prescribed product (medication description)
Use the ART 57 services for resolving the identification of the Products cross-borders.
No constrains have been specified about how each country will determine and provide this information in the issued cross-border ePrescription. For example:
determined by the prescriber as part of the information available in the local drug DB;
assigned when the prescription is transmitted outside the national borders by a software component on the basis of the data present in the prescription; ….

18. Filling the epSOS elements using the Art 57 data
epSOS Data Set
Cyllaron*
Pharmaceutical Product
Amoxicillin and clavulanic acid, 875 mg/125 mg, Tablets, Oral; 20 tablets; ….
The patient receives a prescription for ‘Pharmacillo’ from her Italian doctor….
… she then travels to Greece where she wants to redeem the prescription… 18
(*) Medicinal product names are fictional and for illustrative purposes only..

19. Filling the epSOS elements using the Art 57 data
Proposed harmonization tasks
Adopt the XEVMPD substance vocabulary for resolving the known issues about the identification of the active ingredients.
Allow to use the substance ATC code and the active ingredient data as distinct information
Recently approved EXPAND change proposals support this !
Align the epSOS ATC and EDQM based value sets with the XEVMPD ones
Use the EMA tables of units for generating new value sets to be used in epSOS for filling strengths’ denominators and numerators.
A 1 to 1 relationship between the epSOS and the ART. 57 used units can be defined.

20. Filling the epSOS elements using the Art 57 data
Constraints for the adoption
Country of Affiliation must have in its local database the coded information contained in Art 57 database for its authorised medicines
–or –
Country of Affiliation must perform a call to EMA Art 57 database to retrieve the coded data
Country of Affiliation must upgrade the National Connector
epSOS MVC and MTC have to be upgraded
OpenNCP Semantic Components and Portal and eP scrutiny test tools must be updated
Country of Treatment must have in its local database the coded information contained in Art 57 db for its authorised medicines to fill the eDispensation –or –
Country of Treatment must perform a call to EMA Art 57 database to retrieve the coded data for the eDispensation
Advantage of the adoption
Preparatory to the adoption of ISO IDMP

21. Cross-borders identification with Art. 57 services
Marketing Authorisation
MHN: IT
Italian name: Pharmacyllo*
Authorised by: AIFA
Marketing Authorisation
MPID: GR
Greek name: Cyllaron*
Authorised by: ANSM
Marketing Authorization Number
e.g. IT
The patient receives a prescription for ‘Pharmacyllo’ from her Italian doctor….
… she then travels to Greece where she wants to redeem the prescription… 21
(*) Medicinal product names are fictional and for illustrative purposes only..

22. Cross-borders identification with Art. 57 services
The Pharmaceutical Products are resolved cross- borders using the ART 57 services
The country that issues the prescription identifies the product through the national authorization number
The dispensing country queries the Art. 57 services for obtaining which product(s), in that country, fit(s) with the prescribed one.
Proposed harmonization tasks
Introduce the concept of authorization number in the epSOS data set (as mandatory)
This concept is already present in the implemented model adopted in the epSOS extension.

23. Cross-borders identification with Art. 57 services
Constraints for the adoption
Country of Affiliation who allows only to prescribe by “generics” or by Active Ingredients, must simulate a Dispensation retrieving a registration code of a medicine compliant to the ePrescription
–or –
Country of Affiliation must perform a call to EMA Art 57 database to retrieve the registration data (very unlikely…)
Country of Treatment must perform a call to EMA Art 57 database to retrieve the list of medication equivalent to the receive ePrescription (suggested: through the portal)
eDispensation is built using the registration code of the dispensed medicinal
Advantage of the adoption
Limited changes in OpenNCP and MVC are required
No need for coded data in Country A and B
Conceptually, no changes are needed in the portal display, being the Country B medicinals

24. Conclusions
« It – could – work! » (Young Frankenstein, 1974)

25. Conclusions (1/2)
A medium term solution for improving the EU cross- border eP interoperability based on the Art. 57 Database content and services can be realized.
It covers registered pharmaceutical products
It may evolve towards long terms sustainable future solutions based on IDMP, coherently with the evolution path foreseen by EMA for the Art. 57 and by the openMedicine project.
Two possible - not mutually exclusive - approaches can be thought :
Filling the epSOS elements using the Art 57 data
Resolve the Pharmaceutical Products, cross-borders, using the ART 57 services

26. Conclusions (2/2)
EMA is currently validating the information received in Art57 database and it is also discussing with MSs on how to ensure good data quality minimising the “a posteriori” validation.
EMA is currently liaising with MSs to check the level of completeness of the data received in Art57 database.
EMA will review the business process and the data workflow during the ISO IDMP implementation to improve data quality at source point

27. Fundamental questions from epSOS
Can the EMA work, undertaken because of the pharmacovigilance legislation, contribute towards improving interoperability of databases and safety and interoperability of ePrescriptions?
YES
«It – could – work!»

28. Thank You ! Questions ? Our questions:
Which solution do Member States prefer the most?
Which Member States are ready for either solutions?