Tag Archive for: PSUR

CESP expands in Poland and Greece

Latest news from Poland and Greece for CESP

From 3rd April 2017 it will be possible to submit the following procedures via Common European Submission Portal (CESP) to Poland:

  • Initial Marketing Authorisation Applications (MAAs)
  • Variations
  • Renewals

The submissions may concern national and European procedures (MRP, DCP) both for human and veterinary medicinal products.


Also from 3rd April 2017 the following submissions should be transmitted through CESP for Greece:

  • All submissions for Mutual Recognition/Decentralised Procedures (MRP/DCP)
  • national procedures relating to approvals, variations, renewals, PSURs, ASMFs etc., as well as any other documentation should be submitted using CESP.
  • Responses to deficiencies and any other additional information that can be requested from the EOF within the claims of assessment.



What does this mean for you?

To date in Poland, only submissions concerning initial MAAs were possible via CESP. There are still some national requirements in Poland, however.  All documents that require an original signature can be either submitted

  • in electronic version with a valid electronic signature or
  • must be submitted in parallel to CESP in paper.
  • Documentation once submitted via CESP should be submitted via this channel throughout its whole lifecycle.

For submissions into Greece, additional CD/DVDs are no longer required.  In addition, for each submission, a corresponding reference number will be automatically assigned and will be sent directly to the applicant.


Where can I find more information?

Full details are available on the Polish Ministry’s website (in Polish) here.

Full information is for Greece (in Greek) here.


We can help…

Ivowen are fully equipped to prepare and submit any applications on your behalf.  Please contact us or our EuDRAcon partners for more information and for support of your dossier compilation or updates.

Written by Majella Ryan

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EMA eSubmission Gateway – tips & tricks

Current State of Play

As many of you know, the EMA eSubmission Gateway/Web Client has been mandatory for all submissions for human medicinal products made through the Centralised Procedure since March 2014 and for veterinary products since January 2017.  In addition, all PSUSA/PBRER submissions are also made through this EMA eSubmission Gateway, and have been mandatory since June 2016.

Unfortunately, as many of you also know, there are some glitches and issues with this portal.  Below are the workarounds for some of these glitches.


Contact us

Please feel free to contact us if you need any help submitting through the EMA eSubmission Gateway/Web Client


“Click to send documents totalling more than 10 MB”

To send any submission through the portal and get an acknowledgement (“ACK”) for this submission, you have to use the “Click to send documents totalling more than 10 MB” option.  When you first log in or register for the EMA eSubmission Gateway, and go to the “SEND DOCUMENT” page, this option is not available.  This is down to Java settings and security.  The way around this is to set your Java security settings and exceptions as follows:


Java settings


At the moment, you may find that the “Click to send documents totalling more than 10 MB” option is still not available, even when your security settings and exception list are correct.  The EMA Service Desk has assured me that they are working on this issue, but in the meantime you can follow the instructions below to work around this issue/


  1. Open Internet Explorer and log into EMA portal. Go to “Send document”.
  2. If you see the “Click to send documents totalling more than 10 MB” then continue to send your submission as normal.
  3. If you don’t see the “Click to send documents…” link, like this example, then follow the instructions below:

Click to send missing


3.1       In the top right hand corner is a Settings button that looks like a machine wheel

3.2       Click on this Settings button and then click “F12 Developer Tools”:

F12 Developer tools 1


3.3       If you see that the Document Mode is “11 (default)” like the screenshot below:

Document mode 11

3.4       Change this to “10” and the “Click to send documents…” will appear:

Document mode 10

3.5       You need to leave the F12 Developer Tools window with these settings OPEN until you have completed your submission.  The EMA Gateway Service desk is working on a fix for this problem, but this is the workaround for now.

EMA introduces changes to the QRD templates

The EMA has introduced changes to the QRD templates of the product information that accompany all medicines authorised for use in the EU including package leaflet (PL) and the summary of product characteristics (SmPC). Full details are available here:

Summary of Main Changes:

The changes to Quality Review of Documents (QRD)  templates are detailed in the updated guidance for the pharmaceutical industry. The main modifications are:

  1. the acceptance of combined SmPCs for different strengths of the same pharmaceutical form whereas until now a separate SmPC was required for each strength of the same pharmaceutical form
  2. the dates to be recorded in section 9 of the SmPC (i.e. date of first authorisation and date of latest renewal)
  3. the text to be included in Annex II (for centrally approved products (CAPs) only)
  4. the list of local representatives in the PL may only contain the address of the local representative of the marketing-authorisation holder (MAH) in the Member State where this particular medicine is sold, instead of the contact details of all local representatives in all EU Member States (for CAPs only)

What does this mean for you?

  1. This means that updates to common sections can be managed in one document, instead of multiple documents making life-cycle management much easier and reducing variation preparation time, etc.
  2. These dates only need to go in once, and the only one that will require updating is the renewal date. Since most products ordinarily undergo only one renewal, this date will also only have to be inserted once.
  3. The standard text to be included pertaining to the submission of PSURs has changed. This needs to be updated at the next variation to the your approved QRD text.
  4. This is really good news for all holders of Community Authorisations! (products approved through the Centralised Procedure). Instead of having to list up to 31 local contacts on the printed PIL, it is now permissible to list only the local contacts associated with that particular PIL. For example, for Ireland and UK dual packs, only the Irish and UK local contact need be listed. This will result in serious space savings on individual PILs, and time and efficiency improvements for regulatory affairs departments who need to keep the document life-cycles up to date.

What’s next?

Ivowen have extensive experience with the Centralised Procedure and QRD template changes and maintenance. Please contact us if you would like to discuss any of the above changes or any issues that you might have with your centrally approved products.

Ivowen would also advise that you take this opportunity to check over older approved QRD Annexes and correct any legacy typos, font issues, etc.

Written by Majella Ryan

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Ivowen attends EudraVigilance Training Course on Reporting of ICSRs/SUSARs in the EEA – Suspected Adverse Reactions to Medicines

What is EudraVigilance?

EudraVigilance (http://eudravigilance.ema.europa.eu) is a centralised European database of suspected adverse reactions to medicines that are authorised or being studied in clinical trials in the European Economic Area (EEA) and supports the safe and effective use of medicines (Figure 1 – EudraVigilance System Components).  Adverse reactions (ADRs) can be reported during the development and following the marketing authorisation of medicinal products in the EEA.  The European Medicines Agency (EMA) operates the system on behalf of the European Union (EU) medicines regulatory network.


ICSR, SUSAR and Safety Signals

Specifically, EudraVigilance is a system for managing and analysing information on suspected adverse reactions to medicines by facilitating electronic exchange of adverse event Individual Case Safety Reports (ICSRs) between EMA and all stakeholders including national competent authorities (NCAs), marketing authorisation holders (MAHs) and sponsors of clinical trials in the EEA.  Within clinical trials such a case is referred to as a SUSAR (a Suspected Unexpected Serious Adverse Reaction).  The reporting of ICSRs allows for the early detection and evaluation of possible safety signals leading to improved product information and benefit-risk balance for marketed medicines authorised in the EEA.  A Safety Signal is defined as information on a new or known adverse event that is potentially caused by a medicine and that warrants further investigation.  Signals are generated from several sources such as spontaneous reports, clinical studies and the scientific literature.

Taking into account the pharmacovigilance activities in the pre- and post-authorisation phase, EudraVigilance provides two reporting modules:

  1. The EudraVigilance Post-Authorisation Module (EVPM)
  2. The EudraVigilance Clinical Trial Module (EVCTM)


Figure 1.  EudraVigilance System Components


 Data Publishing, Review and PRAC Evaluation

EMA publishes data from EudraVigilance in the European database for suspected adverse drug reaction reports – http://www.adrreports.eu/.  EMA, NCAs and MAHs are responsible for reviewing EudraVigilance data to detect safety signals.  The Pharmacovigilance Risk Assessment Committee (PRAC) evaluates the safety signals detected in EudraVigilance and may recommend regulatory action as a result – http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000537.jsp&mid=WC0b01ac058058cb18.


What we can do for you:

Electronic reporting of suspected adverse reactions to medicines is mandatory for MAHs and sponsors for clinical trials.  Ivowen can advise and assist you in the following areas of reporting to EudraVigilance along with updating product information for PRAC recommendations:

  • Describe the Registration process with EudraVigilance
  • Create, validate and send safety messages (initial, follow-up reports, nullification reports, literature reports, parent-child , study reports, reports with medical and drug history)
  • Create and send acknowledgments of received ICSR messages
  • Query, view, browse and download safety reports
  • Query, view and browse MedDRA through the EVWEB

Please contact us for further information.


Written by Laura Oakey.



Pharmacovigilance most of all

The European Medicines Agency (EMA) has recently published an overview of pharmacovigilance activities that outlines just how strong and reliable a system we have in the EU. The report was prepared by EMA in collaboration with the National Competent Authorities (NCA).  The report includes quantitative data covering the period between 2015 and 2018 and shows that the European regulatory network for medicines is held accountable for the implementation of the pharmacovigilance legislation.

The measurement of impact is based on a strategy and action plan for measuring the impact of pharmacovigilance activities, adopted by EMA’s safety committee (PRAC) in 2017.

It shows that the EU pharmacovigilance system is strong and protects public health.

 Some key outcomes 2015-2018

  • More than 500 new or updated risk management plans were assessed by the PRAC each year, ensuring the safety monitoring and risk minimisation is proportionate and planned. In addition, nearly 7,000 risk management plans were assessed by the Member States for nationally authorised medicines during the reporting period.
  • Enhanced EudraVigilance database of suspected side effects, resulting in improved reporting and greater analytical power;
  • Evaluation of nearly 9,000 potential signals (information about new or changing safety issues potentially caused by a medicine) by EMA’s signal management team over the period covered by the report, and a similar number of potential signals assessed by Member States;
  • Radical simplification and improvement of the way periodic safety update reports are handled, by establishing a common repository with a single portal for access;
  • Development of criteria to determine when a public hearing on issues of medicines’ safety would be of value, and the successful holding of the first such hearings, for valproate-containing medicines in 2017 and for quinolone and fluoroquinolone antibiotics in 2018;
  • Continued development of the ‘Article 57 database’, which now contains information on more than 800,000 medicinal products authorised through central, decentralised, mutual recognition and national procedures across the European Economic Area.

For more details on the report please refer to EMA web page where you can access the press release issued.

The pharmacovigilance legislation established now reinforces the need for and format of various reports, including:

  • Risk Management Plans (RMP);
  • Periodic Safety Update Reports (PSUR);
  • Post-Authorisation Safety and efficacy Studies (PASS);
  • Pharmacovigilance System Master Files (PSMF).

Should you require assistance with respect to setting up a pharmacovigilance system, or the preparation and submission of pharmacovigilance related data we encourage you to contact us.

Written by Alice D’Alton.

PSUR repository updated

On the 26th of January 2015, the EMA introduced the pilot phase on the use of the XML delivery file for submissions of PSURs via the eSubmission Gateway/Web Client.

This introduction,

1) Simplified package file names for PSURs and

2) Introduced the requirement of an XML delivery file.

The XML delivery file is created in the PSUR Repository user interface

The PSUR Repository user interface is basically broken down into 4 sections:

  • Section 1: Regulatory Activity

This is a simple drop down list and is currently only available for PSUR submissions and Supplementary information which is related to a PSUR submissions.

  • Section 2: Details of assessment procedure

This section requires you to enter the Procedure Number as per the EURD list, all other information (Submission deadline, DLP, Active name, Rapporteur name and Rapporteur country) will prepopulate based on this Procedure Number. Carefully check if all information is correct, if prepopulated information is wrong contact the EMA.

  • Section 3: Product Selection
  1. Select your Submission Format (eCTD or NeeS)
  2. Enter the product name(s) in the section products to which the submission relates for all your products to which the submission relates. This is a drop down menu based on the Art 57 database. Therefore you must first ensure that all your product information entered in the Art 57 database is up to date and correct.
  3. Select your products, enter your procedure number (where relevant) and the sequence number of your submission.
  •  Section 4 Routing information
  1. Enter EMA routing ID (e.g. ESUBPROD) and  your Routing ID (e.g. ESUBPTESTPROD123)
  2. The XML delivery file will always be called xml, this should not be renamed/edited
  3. Save the XML delivery file inside the PSUR submission folder (zipped).
  4. Your PSUR folder should have a meaningful file name and examples of these can be found in Annex 3.
  5. Your Submission file can be send in the normal manner via the eSubmission Gateway/Web Client.

From September 2015, it will be mandatory to use the XML delivery file for all PSUR submission to the EMA via the eSubmission/Web Client.

Please contact us if you require any further information or help with this process.

Written by Fiona Downey.