11/08/2014
EMA/93253/2014
Procedure Management & Business Support
Cover note on XEVMPD Substance controlled vocabulary
following the quality control exercise
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© European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged.
Table of contents
1. Introduction ............................................................................................ 3
2. General principles and definitions ........................................................... 3
2.1. Master substance ................................................................................................. 3
2.2. Synonym and translation....................................................................................... 4
2.3. Duplicate substance .............................................................................................. 4
2.4. Invalid name ....................................................................................................... 4
3. XEVMPD Substance assessment – Scenarios ........................................... 5
3.1. Assessment impacting EV Code .............................................................................. 5
3.2. Assessment impacting name .................................................................................. 6
4. Business process for the implementation ................................................ 7
5. Next steps ............................................................................................. 10
6. Requesting a new substance/translation/synonym .............................. 11
6.1. Requests for a new approved substance to be inserted in the XEVMPD ...................... 11
6.2. Requests for an update of an existing substance to add substance translation or alias 11
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1. Introduction
As part of the efforts to provide high quality Article 57(2) data, the Agency performed an activity to
de-duplicate substance names available in the XEVMPD Substance Controlled Vocabulary (CV). The
objectives of this activity have been as follows:

To identify and merge all duplicated substance names;

To collate all substance names received via Art57 helpdesk since March 2012 and substance names
currently available as historical records only;

To reconcile and include any substance names and translations reported in Individual Case Safety
Reports (ICSRs).
The following activities are out of scope of this phase of the quality control exercise:

The validation of substance reference information available in EVWEB (e.g. CAS number, molecular
formula); and

The completion of information in the existing substance record in line with the official reference
sources and addition of any missing translations.
The purpose of this document is to provide Marketing Authorisation Holders (MAHs) with the outcome
of the substance name de-duplication activity and an explanation on how to consult the XEVMPD
substance controlled vocabulary list available in the Controlled Vocabularies section of the Data
submission on authorised medicines - Guidance documents webpage.
Following the validation performed by the Agency, the XEVMPD substance controlled vocabulary
contains the complete list of the substance assessment and mapping data. Specifically, the purpose of
this file is to allow MAHs submitting Article 57 medicinal product information via EMA Gateway to
perform an analysis and plan for the implementation of the remapping of substance names in their inhouse systems. In addition, the actions to be performed by EVWEB users (where applicable) are also
explained.
2. General principles and definitions
2.1. Master substance
Among the cluster of potentially duplicated substance names, the master substance is defined
according to the definitions and classes referred to in the ISO 11238:2012 IDMP standard, and based
on the validation against internationally recognised reference sources.
The ‘Master Substance EV Code’ is selected from the “Cluster of substance names” and it is selected
based on the following principles:

The substance name with the status “checked” and most frequently referenced in Article 57(2)
medicinal product submissions;

Preferably, the preferred name should be an International Nonproprietary Name (INN)/ European
Pharmacopoeia (Ph. Eur.) or other internationally recognised name.
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2.2. Synonym and translation
Synonym refers to a valid alternative name according to the official reference source. The synonym
substance name may be used to refer to the substance preferred name.
Translation is defined as a valid alternative term of the master substance name or the associated
synonym in another European language, according to an official reference source. For each of the
substance names assessed, indication if it is a translation as well as the applicable language is
available.
2.3. Duplicate substance
Duplicate substance is defined as a name that refers to the same substance and reference
information, where the name’s EV Code does not equal to the EV Code of the selected master
substance name. This is in line with the substance definitions and classes, as described in the ISO
2012:11238 IDMP standards on substances, and the review of reference sources.
2.4. Invalid name
Substances in the XEVMPD should be in line with specific rules and naming conventions. Where these
are not applicable, the substance name is considered not valid. Examples of not accepted substance
names are multiple substance names, substance classes and product names.
These names will be removed from the XEVMPD substance CV and they should not be used for future
submissions.
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3. XEVMPD Substance controlled vocabulary description and
assessment – Scenarios
The following paragraph should be read in conjunction with the excel file “EudraVigilance eXtended
Medicinal Product Dictionary (XEVMPD) substances”.
Sheet 1_Current + New Substance CV contains the valid substance controlled vocabulary that is
updated with the new substance names on regular basis. In column “G” of this sheet newly inserted
substance names and/or EV codes since the last publication of the CV can be identified.
Sheet 2_Deprecated Substance names incudes all the substance names that have been deprecated
since the last publication of the CV and sheet 3_EVCodes Nullified includes those EV Codes nullified
since the last publication.
The sheets 4-6 are aimed to explain the de-duplication performed by the Agency and provide guidance
on the actions that need to be performed by MAHs as detailed in section 3.2 and 5 of this cover note.
3.1. Assessment - Scenarios
3.1.1. Assessment impacting EV Code
The below table provides the different scenarios following the substance validation.
Scenario
Action performed in the
Action to be performed by
description
XEVMPD by the Agency
the MAH
Sheet
The EV Code is a
4_Remapped
duplicate of the

The previous Substance
EV Code “Before the

databases to link the
EV Codes
master substance
Substance Quality
authorised medicinal
(EV Code)
Control” has been
product referencing the
remapped to the master
previous EV Code to the
substance EV Code
master substance EV Code
“After the Substance
Quality Control”;

To re-align their in-house
(Gateway users only);

Not use the previous
All products referencing
substance EV Code in
the previous EV Code
future submissions.
were re-linked to the
Master substance EV
Code

The previous EV Code
has been nullified and
will not be available for
use in future
submissions.
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Sheet
The name and its

EV Code nullified at the

Not to use the substance
5a_EV Codes
EV Code are not
end of the de-
name/EV Code in future
to be
valid, and cannot be
duplication activity.
submissions as it is not
nullified
recoded against a
includes
valid substance EV
substance EV
Code/Name.
valid.
Codes not
used in any
medicinal
product(s)
Sheet
The name and its

5b_EV Codes
EV Code are not
MAHs to re-link their
medicinal product
to be
valid, and cannot be
medicinal product(s) to
maintenance submission,
nullified
recoded against a
the most suitable and
MAHs should re-submit the
includes
valid substance EV
valid substance EV
medicinal product(s)
substance EV
Code/Name.
Code/Name;
containing the EV Code to
The EMA will not
be nullified to reference
medicinal
perform any action in
the most suitable master
product(s)
the database until the
substance EV Code.

Codes used in
The EMA will ask the

In the context of the
re-submission by the
concerned MAHs is
completed;

Following the resubmission by MAHs,
the substance EV Code
will be nullified, and will
not be available for use
in future submission.
3.1.2. Assessment impacting name
This table provides the different scenarios following the substance name validation.
Scenario
description

Action performed in the
Action to be performed by the
XEVMPD by the Agency
MAH
The Agency reconciled

Update all substance EV Codes to
Sheet
Valid preferred
1_Current
name,
all the assessed
include all the valid names
+ New
synonym/alias,
substance names and
present in sheet 1_Current +
Substance
translation
translations. The
New Substance CV
CV
according to the
outcome of this exercise
official reference
is the list of Master EV
source
Codes with their
corresponding substance

The substance EV Code “Before
the Substance Quality Control” is
provided only for reference.

Sheet 1_Substance CV should be
names and translations,
used for the maintenance of the
which are published in
CV.
the substance Controlled
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Scenario
description
Action performed in the
Action to be performed by the
XEVMPD by the Agency
MAH
Vocabulary.

The name has been

This list is only provided to MAHs
Sheet
The name is not
6_Invalid
valid according
removed from the
for information and future
substance
to the reference
XEVMPD substance CV,
reference. The list needs to be
names
sources
and it will not be
checked before submitting
available to users for
substance requests via
future submission.
MDMS@ema.europa.eu (see
section 6. of this document).

Not to use the listed substance
names in future medicinal product
submissions.
4. Business process for the implementation
This section describes the proposed business process to reconcile medicinal product information
available in the XEVMPD with MAHs in-house systems.
In addition, it outlines the process to be followed by all users to validate the substance referenced in
the Article 57 medicinal product records in the context of the medicinal product maintenance
submission.
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Business process
Gateway users
Automatic script
1.Update in your
own system all the
products
referencing the
previous substance
EVCodes that need
to be remapped to
new master
EVCodes.
Use ‘Substance
EVCODE to be’ in
sheet 4_
Remapped EVCodes
2.Nullify in your
substance CV the
duplicate substance
EVCodes


Nullify previous substance
EVCodes’ in sheet 4_
Remapped EVCode
Nullify substance EVCode of
sheet 5a_ EVCode to be
nullified
All Users
4. In the context of the
medicinal product
maintenance submission
3. Update the
substance EVCodes
in your substance
CV to include all the
valid names
Use sheet
1_Current + New
Substance CV
4.a Validate that the
relinked products
due to above
procedure still
reference the right
substance
4.b Relink all products referencing to
substance EVCodes that should be
nullified to a valid EVCode
The products that
need to be relinked
in this step are
referencing to
substance EVCodes
present in sheet
5b_EVCodes to be
nullified
NOTE: all the substance names in sheet
6 _Invalid substance names are not
available for future submission, so the
list need to be checked before
submitting substances requests via
MDMS@ema.europa.eu.
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STEP
ACTION
Gateway users
1.
As regards the medicinal products submitted under Article 57(2) legal obligation, all
referenced EV Codes should be replaced with the Master Substance EV Codes. Using your
system, update [operation type 'Update (2)'] all products referencing the current
substance EV Codes that need to be remapped to the new EV Codes.
MAHs should check that the new substance name/EV Code is correct and still valid for
that product, and amend as applicable as part of the maintenance submission.
Use column " previous Substance EV CODE before the substance Quality Control" in sheet
4_ Remapped EV Codes
NOTE:
The Agency will perform the re-link of duplicated approved substances on authorised and
development medicinal products in the XEVMPD.
2.
In your substance CV, nullify [operation type 'Nullify (4)'] the duplicated substance EV
Codes.
3.

Nullify "Current substance EV Codes" in sheet 4_ Remapped EV Codes

Nullify substance EV Code of sheet 5a_ EV Codes to be nullified
Update [operation type 'Update (2)'] the substance EV Codes in your substance CV to
include all valid names.
Use sheet 1_Current + New Substance CV
The list will be used to upload your system.
All Users
4
In the context of the medicinal product maintenance submission, please check that
following the process described in steps 1 – 3, the re-linked products still reference the
correct substance.
5
Re-link all products referencing the substance EV Codes that should be nullified to a valid
EV Code.
The products that need to be re-linked in this step are referencing the substance EV
Codes present in sheet 5b_ EV Code to be nullified.
When the products are updated, these substance EV Codes will be nullified by the
Agency.
NOTE:
All substance names in sheet 6_ Invalid substance names are not available for future
submission. This list is provided for information only and should be checked before
submitting substances via MDMS@ema.europa.eu (see section 6. of this document).
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5. Next steps
From 16 June 2014, marketing-authorisation holders will need to update, complete and improve the
quality of the information. This will involve the completion of the previously submitted information with
the additional data elements, as well as checking the quality of all information in line with the updated
reporting requirements. MAHs will need to complete this process by the end of 2014.
For full details on the reporting requirements during this phase, please see the Legal Notice on the
Implementation of Article 57(2) of Regulation (EC) No. 726/2004, and the detailed guidance
documents available on the Agency's website.
NOTE: During this phase, marketing-authorisation holders will also need to continue to submit
information on new marketing authorisations granted after 2 July 2012 as soon as possible and no
later than 15 calendar days from the date of authorisation (i.e. 15 calendar days from the date of
notification of the granting of the marketing authorisation by the competent authority).
If it is not possible for MAHs using the EudraVigilance Gateway to submit this information within the 15
calendar days due to the XEVPRM schema changes, the Agency should be informed of their expected
submission plan by submitting an email notification to the email address
Art57submissionplan@ema.europa.eu. The following information must be provided:

MAH name and Headquarter organisation ID (i.e. the ID specified by the organisation during the
registration process to uniquely identify each organisation in EudraVigilance. This ID is used to
send/receive product/safety reports as per your organisation’s profile.);

Volume of data (i.e. number of product records to be submitted during the specified time frame);

Timeline for submission (i.e. the start date and completion date of the electronic submission).
Following the update, completion and improvement of the quality of data by the end 2014, marketingauthorisation holders will need to maintain the data in the database. This phase will begin in January
2015 at the latest.
Marketing-authorisation holders will need to:

Continue to notify the Agency of any new marketing authorisations within 15 calendar days from
the date of authorisation (i.e. 15 calendar days from the date of notification of the granting of the
marketing authorisation by the competent authority);

Notify the Agency of any amendments to the terms of marketing authorisation by means of the
same business processes and within 30 calendar days from the date on which the changes are
authorised.
For full details on the reporting requirements during this phase, please see the Legal Notice on the
Implementation of Article 57(2) of Regulation (EC) No. 726/2004, and the detailed guidance
documents available on the Agency's website.
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6. Requesting a new substance/translation/synonym
6.1. Requests for a new approved substance to be inserted in the XEVMPD
Providing that an approved substance is not listed in the XEVMPD substance controlled vocabulary list
(sheets 1_Current + New Substance CV and 6_ Invalid substance names) available in the
'Controlled Vocabularies' section of the Data submission on authorised medicines - Guidance
documents webpage, or in the XEVMPD substance look-up table, MAHs should submit their substance
requests to MDMS@ema.europa.eu.

Request for an insert of a new approved substance should be stated in the email subject;

The substance name in English, substance class and reference source need to be included in the
request.
Please see the EudraVigilance eXtended Medicinal Product Dictionary (XEVMPD) substance classes
Controlled Vocabulary published on the Agency's website for further information on available
substance class values.
Please see the EudraVigilance eXtended Medicinal Product Dictionary (XEVMPD) reference sources
Controlled Vocabulary published on the Agency's website for further information on available
reference source values.
Should the Summary of Product Characteristics (SmPC) or Package Leaflet (PIL) be used as the
reference source, the SmPC/PIL should be attached to the request.

If requesting that a translation is added to an approved substance entry, the translation and
the applicable language information should be included in the request. For languages where
the grammar uses declined forms, the nominative singular form (i.e. not declined) of the
translated substance name should be provided.

If requesting that an alias is added to the substance entry, the alias and reference source
should be included in the request.
The Agency will process the request in the XEVMPD and provide the MAH with the master substance EV
Code to be referenced in their product entry as part of the electronic submission of medicinal product
information under Article 57(2) provision.
6.2. Requests for an update of an existing substance to add substance
translation or alias
MAHs should retrieve the substance EV Code in the XEVMPD substance controlled vocabulary list (sheet
1_Current + New Substance CV) available in the Controlled Vocabularies section of the Data
submission on authorised medicines - Guidance documents webpage, or in the XEVMPD substance
look-up table, and submit their requests to add the substance translation or alias to
MDMS@ema.europa.eu.

Request for an update of an approved substance should be stated in the email subject;

The translation and the applicable language information should be included in the request. For
languages where the grammar uses declined forms, the nominative singular form (i.e. not
declined) of the translated substance name should be provided.
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
If requesting that an alias should be added to the substance entry, the alias and reference
source should be included in the request.
The Agency will process the requests in the XEVMPD.
MAHs should use the master EV Code of the approved substance with the preferred name in English in
their product entries as part of the electronic submission of medicinal product information under Article
57(2) provision.
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