Pharmacovigilance Archives | Page 2 of 2 | European Regulatory Affairs Specialists

EMA eSubmission Gateway – tips & tricks

28th August 2017

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:

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/

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

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”:

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

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

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.

Clinical Trials Regulation EU No 536/2014 – What does this mean for you?

8th May 2017

When the Clinical Trial Regulation (No. 536/2014) comes into effect in 2018, there will be a major change on how clinical trial applications are submitted and how clinical trials are conducted in the EU.

The goal of the new Regulation is to create an environment that is favourable to conducting clinical trials in the EU, with the highest standards of safety for participants and increased transparency of trial information.

Below you will find a brief summary of the changes:

Directive 2001/20/EC (Current)

Multiple submission for one trial (1 submission per each MS)
Double submission with a MSC: to NCA and EC
Individual assessment by Each MSC with no IT collaboration tool available
No Single MSC decision (NCA and ECs)
Limited EudraCT data availability to the public

Regulation 536/2014 (New)

Single e-submission to all MSCs
Harmonised dossier for one trial and
e-submission of structured data and documents by MSCs
Specific timeline
Joint assessment for PART I facilitated by collaboration tool
Single MSC decisions
Single web-based EU portal
Distribution of the burden among users
View all CT relation information

Transition period (3 years) Directive 2001/20/EC (current) to Regulation 573/2014

Starts when Regulation becomes applicable (~ Oct 2018)
1^st Year: Clinical Trials can be submitted under old/current (Directive) or new (Regulation) system
2^nd & 3^rd Year: Trials authorised under old system can remain under that system, New/initial Clinical Trials should comply the Regulation System
All Clinical Trials to switch to the Regulation 3 years after implementation (~ Oct 2021)

Typical Documents to be submitted:

Part I: Cover letter (very important), EU AF, Protocol, IB, GMP compliance documents, IMPD, Auxiliary Medicinal Product Dossier, Scientific Advice, PIPs, and labelling, proof of payment, etc.
Part II: Recruitment arrangements, SI/ICF/ICF procedure, suitability of the investigator, suitability of the facilities, proof of insurance cover or indemnification, financial and other arrangement, proof of payment, etc.

Part I Timetable Coordinated assessment (also applies to Mono-national Clinical Trials)

Day 0: Validation
D26: Draft Part I Assessment Report made available by the RMS (reporting MS) to the CMS
D38: All CMS share considerations
D45: RMS finalises the Part Assessment Report
D57: Sponsor submits response (w/n 12days)
D69: Co-ordinated assessment between MSs (12 days)
D76: RMS files conclusion (7days)

Part II Timetable National evaluation

D0: Validation

D45: Final assessment report from each MSC submitted

D57: Sponsor submits response

D76: Final assessment by the MSC shall be performed (w/n 19 days)

Submission of Part I and II in parallel (recommended) or submission of Part I followed by Part II (not less than 2 years after Part I)

Important Notes:

New MSs can only be added after the notification date of the initial authorisation decision
Withdrawal of MS: the whole application has to be withdrawn and resubmitted

Transparency:

EU Database will be publically accessible by default, with exceptions justified on any of the following grounds

Protection of personal data
Protection of commercially confidential information in particular taking into account the MA status of the medicinal product, unless there is an overriding public interest in disclosure
Protecting confidential communication between Member State in relation to the preparation of the assessment report
Ensuing effective supervision of the conduct trial Member States

Where can I find more information?

Information on Clinical trials – Regulation EU No 536/2014, General information, Guideline EU

Clinical Trial Portal and Database, Transparency, Safety reporting, Clinical trials conducted outside the EU, Contact points can be found here: https://ec.europa.eu/health/human-use/clinical-trials/regulation_en

We can help…

Ivowen are fully equipped to submit for Clinical Trials Applications on your behalf. Please contact us for more information and for support of your dossier compilation or updates.

Written by: Fiona Downey

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

30th November 2016

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:

The EudraVigilance Post-Authorisation Module (EVPM)
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.

PSUR repository updated

25th August 2015

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

Select your Submission Format (eCTD or NeeS)
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.
Select your products, enter your procedure number (where relevant) and the sequence number of your submission.

Section 4 Routing information

Enter EMA routing ID (e.g. ESUBPROD) and your Routing ID (e.g. ESUBPTESTPROD123)
The XML delivery file will always be called xml, this should not be renamed/edited
Save the XML delivery file inside the PSUR submission folder (zipped).
Your PSUR folder should have a meaningful file name and examples of these can be found in Annex 3.
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.

EMA eSubmission Gateway – tips & tricks

Current State of Play

Contact us

“Click to send documents totalling more than 10 MB”

Clinical Trials Regulation EU No 536/2014 – What does this mean for you?

Where can I find more information?

We can help…

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

PSUR repository updated

Need help with all the regulatory jargon?

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