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29 June 2015
EMA/52449/2015 v. 2.1
User Guidance for Marketing Authorisation Holders
(MAHs) for PSUR Repository
30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom
Telephone +44 (0)20 3660 8427 Facsimile +44 (0)20 3660 5555
E-mail [email protected] Website www.ema.europa.eu
An agency of the European Union
Table of contents
1. Introduction ............................................................................................ 4
2. The submission process ........................................................................... 5
2.1. PSUR submission for product lifecycle maintained using Electronic Common Technical
Document (eCTD) format including examples of workaround solutions and constraints ........ 5
2.1.1. Example 1: Duplicate CAP/NAP – eCTD format: ..................................................... 5
2.1.2. Example 2: MRP/DCP authorisation – comprehensive model (harmonised approach)
using eCTD format: ..................................................................................................... 5
2.1.3. Example 3: MRP/DCP/National authorisation – eCTD format: .................................. 7
2.2. PSUR submission for product lifecycle maintained using Non-eCTD Electronic Submission
(NeeS) format ............................................................................................................ 8
2.3. PSUR containing a mixture of products maintained using eCTD and NeeS formats ........ 8
2.4. PSUR submission of single, pure NAP (product authorised in just one member state) .... 8
3. Create delivery file screen ....................................................................... 9
3.1. Product Selection ............................................................................................... 12
3.1.1. Filtering authorised product listing ..................................................................... 12
3.1.2. Scenario 1: The submission relates to a centrally authorised product (CAP) which will
always require eCTD submission format or a Nationally Authorised or MRP/DCP product in
eCTD format ............................................................................................................ 13
3.1.3. Scenario 2: The submission relates to nationally authorised product (NAP) and
requires NeeS submission format ................................................................................ 15
3.1.4. Scenario 3: The submission relates to a pure, single NAP submission outside the EU
single assessment ..................................................................................................... 16
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Document History
Version
Date
Changes applied
Author
1.0
04/11/14
Original – documented usage of production selection
Wasif Sabir
function
1.1, 1.2
05/11/14
Added “Create delivery file” screens and annotation
Wasif Sabir
1.3
06/11/14
Added section on eSubmissions and restrictions around
Wasif Sabir
submission formats
1.4
07/11/14
Reviewed and updated with additional comments on
eCTD and NeeS restrictions. Also added note regarding
file naming convention not required for PSUR and
Wasif Sabir,
Kristiina Puusaari
Supplemental Info submissions.
1.7
11/11/14
Added the correct EMA routing ID and URL for create
Wasif Sabir
delivery file
2.0
17/04/15
Updated
2.1
05/06/15
Updated to add information on how to submit MRP/DCP
Kristiina Puusaari
submissions in eCTD format
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1. Introduction
This document serves as a simple guide for applicants to submit PSUR documents. It highlights the
restrictions and conventions that users need to be aware of when generating submission and delivery
files.
It also describes the existing constraints and workaround solutions to enable submissions to the
repository.
The document assumes prior knowledge of the eSubmissions gateway processes and will therefore
focuses on the process of creating delivery files to be included in the submissions.
Formal communication regarding the changes to the PSUR submission process will be presented via the
eSubmissions website.
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2. The submission process
The main change to the submission process via eSubmission Gateway to the PSUR Repository is that
the MAH is required to include a delivery file in the submission package instead of using a filenaming
convention like for other procedure types.
At a high level it is a two-step process:
1. Create and download the delivery file for the submission by navigating to create delivery file
screen. See Create delivery file screen section.
2. Add the delivery file (without renaming it) to the top-level folder of your document package
and submit this document package via the existing eSubmissions Gateway / Web Client. See
eSubmission Gateway website for detailed guidance on how to register and use the gateway.
Note: The filenaming conventions for PSUR submissions are not validated when a delivery file is
included in the submission and hence a simplified filenaming convention can be used for submissions
to the PSUR Repository. Please see examples of these simplified filenames in Annex 3.
2.1. PSUR submission for product lifecycle maintained using Electronic
Common Technical Document (eCTD) format including examples of
workaround solutions and constraints
If a submission contains more than one product and these are managed in eCTD format, then a
new delivery file and a separate submission is required for each product.
There are a range of possible scenarios in which eCTD format could be used spanning across different
marketing authorisation types. The following examples expand on the particularities of each possible
combination in order for applicants to fully understand the submission requirements in each case.
2.1.1. Example 1: Duplicate CAP/NAP – eCTD format:
A PSUR covers centrally or nationally authorised duplicate products; product A and product B
which are both managed using a separate eCTD product lifecycle. A separate submission is
required for each product to ensure continuity of the eCTD lifecycle. A separate delivery file
needs to be created and attached for each submission.
2.1.2. Example 2: MRP/DCP authorisation – comprehensive model
(harmonised approach) using eCTD format:
A PSUR covers several products authorised via MRP/DCP procedure managed using a single
harmonised eCTD lifecycle, this is also known as the ‘Comprehensive model’ which includes all
strengths in all member states (MS) i.e. where the same sequence number is used for mutual
submissions.
If all strengths in all MS are entered in Art. 57 database with same product short name
‘Wonderdrug’ under which you can select the full product names per MS (for example
‘Wonderdrug MS1, WonderDrug MS2 and WonderDRUG MS3) one xml delivery file can be
created and just one single submission can be made.
See example:
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If the ‘national products’ belonging to this single MRP/DCP product have been entered in Art.
57 as separate entries i.e. not under same product short name ‘Wonderdrug’, but as
‘Wonderdrug SuperMAH, WonderDrug SuperMAH and WonderDRUG SuperMAH it is not
possible to select multiple products in the product short name level for eCTD submissions
due to a limitation in the user interface. It is therefore not possible to include them in the same
delivery file.
In order to reflect all the relevant products in the repository the same eCTD sequence would
need to be submitted multiple times with relevant xml delivery files.
Note: See below for guidance if your submission requires multiple submissions for same
procedure from same MAH in eCTD format.
Delivery file 1 for Package 1:
Delivery file 2 for Package 2:
Constraint and workaround related to submission of multiple eCTD submissions for
same procedure with Harmonised eCTD lifecycle:
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Due to an issue with the EMA eCTD review tool, the EMA review system cannot at the present
process submissions for the same PSUSA procedure which are sent with the same sequence
number from the same MAH. In these cases the review tool assumes these are the same
submission and rejects the 2nd and subsequent submissions. Due to this issue only the 1st
submission would be accepted, and the subsequent submissions would fail at entry point. Until
this issue is addressed (planned for August 2015), please submit just one single package
and indicate a maximum number of ‘product full names’ on the xml delivery file.
In order to ensure that the full product list is available both to the EMA and MS for assessment
and administrative purposes, the MAH is requested to list all relevant products in the Annex I
of the Formatted table Template included in the submission cover letter. Please mention in the
cover letter that due to a technical issue not all products included in the PSUR submitted are
included in the xml delivery file so that the EMA procedure manager and the rapporteur
assessment teams who are reviewing the submissions to the repository and the Annex I can
confirm the scope of the procedure.
Important note: During the transitional period, until the use of the PSUR repository becomes
mandatory, you should submit the package as usual to the relevant member states using their
preferred submission mechanism as per the current submission requirements for the
MRP/DCP/Nationally Authorised Products.
The above issues with the product selection i.e. to be able to select multiple MRP/DCP/NP eCTD
products on the ‘product short name’ level will be addressed in a future release planned for
Q32015.
2.1.3. Example 3: MRP/DCP/National authorisation – eCTD format:
If you have prepared just one PSUR document covering multiple different products with
separate individual lifecycles (not the comprehensive model) you will need to prepare an xml
delivery file for each package. If the sequences have different sequence number each, these
can be sent to the PSUR repository, however, it is very important to send these in ascending
order, for example; if the PSUR covers 3 different products marketed in 3 countries and for
example Product A from MS1 is sequence 0005, Product B from MS2 is sequence 0015 and
Product C from MS3 is sequence 0030 they should be sent in that particular order to avoid
rejection at entry point.
As detailed in the constraints above; the EMA eCTD review tool cannot accept submissions for
the same PSUSA procedure from the same applicant which are sent with the same sequence
number. If the submission sequences for these separate products have the same sequence
number the review tool assumes these are the same submission and it will reject the 2nd and
subsequent submissions. This technical issue will be addressed in a future release planned for
Q32015.
Constraint and workaround related to submission of multiple eCTD submissions for
same procedure with separate, individual eCTD lifecycles:
As a workaround in this particular case, all the sequences other than the first one which can be
submitted with the delivery file, should be sent just using the filenaming convention (see
Annex 1) until the technical issue is solved. This will prevent automated rejection by the review
tool. In order to complete the repository content for that particular procedure the EMA will
manually upload the submission in to the PSUR repository that are received without the xml
delivery file. MAHs are required to list all relevant products in the Annex I of the Formatted
table Template included in the submission cover letter. Please mention in the cover letter that
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due to a technical issue not all products included in the PSUR submitted are included in the xml
delivery file so that the EMA procedure manager and the rapporteur assessment teams who
are reviewing the submissions to the repository and the Annex I can confirm the scope of the
procedure.
This technical issue will be addressed in a future release planned for Q32015.
2.2. PSUR submission for product lifecycle maintained using Non-eCTD
Electronic Submission (NeeS) format
Due to the different nature of co-existing electronic formats, products maintained in NeeS format do
not share the same level of constraints as those maintained in eCTD. In light of this, product lifecycles
that are maintained in NeeS format allow the same submission to be used for multiple products. In the
case of MAH having created a single PSUR for multiple products only one submission needs to be
prepared and one delivery file can be created listing all products. See section 3.1.3. below for detailed
instructions on how to create xml delivery file in this scenario.
2.3. PSUR containing a mixture of products maintained using eCTD and
NeeS formats
When a PSUR contains multiple products that are maintained in different electronic formats it is not
possible to combine the submission for these products and each will need to be submitted with
different, relevant delivery file. A solution to enable sending of ‘multiple zip packages at once is
currently under investigation by the EMA. For example, a PSUR contains the following products:
Product name
Lifecycle format
Authorisation procedure
Product A
eCTD
CAP
Product B
eCTD
CAP
Product C
NeeS
NAP
Product D
NeeS
NAP
Product E
eCTD
NAP
In this example 4 delivery files need to be created and four separate submissions must be made:
•
One for each eCTD lifecycle for Products A, B and E.
•
One for both NeeS products: Products C and D.
See section 3.1.1.
2.4. PSUR submission of single, pure NAP (product authorised in just
one member state)
At a high level the process is exactly the same as for PSURs included in an EU PSUR Single
Assessment, see above.
The rules for product selection are the same; please see sections 2.1-2.3 above.
It should be noted that it is not possible to submit a single NAP which is not part of EU Single
Assessment using the existing existing filenaming conventions from Annex 1 or the new simplified
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filenaming convention as per Annex 3. An xml delivery file must be created for submission to the PSUR
repository.
3. Create delivery file screen
Prior to the creation of the delivery file it is recommended that the users create a separate folder
named after the product for each delivery file that will be needed. By saving each delivery file in their
relevant folder applicant will ensure that the delivery files are not overwritten.
Note the delivery file name must not be amended. It should always be called “delivery.xml”.
Section
One
Section
Two
Section
Three
Section
Four
The screen is divided into four sections:
Section
Section
Section
Section
1:
2:
3:
4:
Regulatory activity and type of assessment
1
Details of the assessment procedure
Product selection
Routing information
The user will be required to complete each field in each section.
1
This section will change to display “Non-EU single assessment” if the checkbox in section one is deselected
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Step
Description
1
Select regulatory activity.
2
Select whether the submission is for single assessment.
Notes
The checkbox is ticked by
default
When checkbox is
cleared the screen will
change to allow the user
to fill in the Member
State and Data Lock
Point (DLP) for the local
country’s assessment
3
Select the PSUR procedure number as in EURD list by
typing at least 4 characters, for example 0000.
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4
Select the submission format.
5
Complete the product selection steps.
See 3.1.
6
Select the destination of the submission package.
See eSubmission Gateway
guidance for more information
on the options available for
the routing ID.
7
Select the EMA routing ID.
Dropdown menu
8
Type in your Gateway Routing ID.
This is the routing ID that was
given to you when you
registered for the
eSubmissions Gateway.
9
Click “Generate Delivery File” and save the file to your local
The delivery file name must
machine.
not be amended. It should
always be called
“delivery.xml”.
10
Add the delivery file to the submission ZIP file package and
The delivery file is named
submit via the eSubmissions gateway.
"delivery.xml" and its name
must be preserved. The file
must be placed in the top
level of your ZIP package.
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3.1. Product Selection
Product selection is the process is identifying the products which are relevant to a particular PSUR
submission in the MAH user interface. The product selection scenarios described below apply to both
EU and non-EU single assessment.
3.1.1. Filtering authorised product listing
Once you have selected your product name the system will display the full list of authorised products
that relate to that name according to the Extended Medicinal Product Dictionary (XEVMPD), also known
as Art. 57 database.
If there are too many products listed you can further filter the results to narrow down the list and find
the specific items that are interested in. The system allows for the use of wildcard characters when
applying a filter. For example, the product full name in the screen extract below shows that you can
display only the 10mg strength products for a particular MAH and country.
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3.1.2. Scenario 1: The submission relates to a centrally authorised product
(CAP) which will always require eCTD submission format or a Nationally
Authorised or MRP/DCP product in eCTD format
Step
Description
Notes
1
Select submission format from the dropdown list – eCTD –
Screen extract 1
2
Type in some characters from the product short name for which you are
Screen extract 1
submitting, e.g. Wonderpill
3
Select the relevant product short name.
Screen extract 1
Screen extract 1 – Product short name (invented name) selection
Step 1
Step 2
Step 3
4
Click on the product name shown. This will show a list of the products at
Screen extract 2
the presentation level. The list can be hidden by clicking the name of
the product again. (See screen extract below)
5
All centrally authorised products (CAPs) have an “H/C” number in
Screen extract 2
following format: EMEA/H/C/123456. This number is normally available
in the field called “EMA Product number/MRP/DCP number”. This must
be added by the applicant in the full 6 digit format in the field labelled
as “EMA Number” and indicated by the label “A” in picture below.
6
Provide the sequence number (indicated by the label “B” in the picture
Screen extract 2
below).
For eCTD submissions this is the next available sequence number in the
product lifecycle.
7
Select one or more of the products that are listed in the PSUR document
Screen extract 2
being submitted. You can select all the products by clicking beside the
column header "MAH Name" (indicated by label “C” in the picture below)
or you can select individual products by clicking on the corresponding
rows (indicated by label “D” in the picture below). For eCTD
submissions only one product short name can be selected. It is
not possible to add NeeS submissions as part of the eCTD delivery file
and a separate delivery file and separate submission must be prepared.
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Screen extract 2 - Show and select product full names
Step 4
B
A
C
D
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3.1.3. Scenario 2: The submission relates to nationally authorised product
(NAP) and requires NeeS submission format
Step
Description
Notes
1. Select submission format from the dropdown list – NeeS.
Screen
extract 3
2. Type in some characters from the product short name for which you are
submitting.
Screen
extract 3
3. Select the relevant product short name from the list.
Screen
extract 3
4. Repeat steps 2 & 3 above until you have the list of product names that match
the content of your PSUR/Supplemental Info document.
Screen
extract 3
Screen extract 3 - Add multiple products
1. Click on the product name shown (or anywhere in the product row) to show the
list of full product names at the presentation level. The list can be hidden by
Screen
extract 4
clicking the name of the product again.
2. Provide the sequence number at the product short name level.
As the NeeS submission sequence number is not linked to the submission
Screen
extract 4
envelope, this information is requested for the use of the NCAs who can use
the sequence number relevant for each product when uploading submissions to
their review systems.
The submission can only contain one zip file that is shared between the
products. It is not possible to send a package that contains one delivery file for
multiple different zips that are sent together. (See screen extract below).
3. Select one or more of the products that are listed in the PSUR document being
submitted. You can select all the products by clicking beside the column header
"MAH Name" (indicated by label “C” in the picture below) or you can select
individual products by clicking on the corresponding rows
4. Repeat steps 5 to 7 for each product added to the list in step 4.
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Screen extract 4 - Show and select product full names
3.1.4. Scenario 3: The submission relates to a pure, single NAP submission
outside the EU single assessment
Step
Description
Notes
1
Select regulatory activity.
2
Ensure you untick the checkbox to reflect that the
The checkbox is ticked by
submission is for single assessment.
default
When checkbox is
cleared the screen will
change to allow the user
to fill in the Member
State and Data Lock
Point (DLP) for the local
country’s assessment
3
Select the Member state where product is authorised
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3
Select the PSUR data lock point
4
Proceed with product selection as in 3.1.2 or 3.1.3
See section 3.1.2 and 3.1.3
depending on the submission format (eCTD/NeeS)
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