1. EVDAS en EVWEB: raak er niet in verstrikt
15 mei 2018, PPN
Anja van Haren EudraVigilance Coördinator
EVDAS en EVWEB: raak er niet in verstrikt

2. Acknowledgement
These PowerPoint slides are based on materials from the European Medicines Agency. Reproduction was permitted provided the source is acknowledged.

3. EVDAS for signal management Closure
Outline
Introduction
EVWEB for downloading
EVDAS for signal management
Closure

4. MAH access to EudraVigilance.

5. > 10 million cases in EudraVigilance
MAH access to EudraVigilance
Download ICSRs (XML format) ICSR forms
e-RMRs (since 22 Feb 2018) ICSR line listings
ICSR forms
> 10 million cases in EudraVigilance

6. CIOMS I form -> ICSR form
16 January 2019
CIOMS I form -> ICSR form
ICSR form
E-RMR and line listing are based on level 1 access => all outputs are the same regardless of which MAH is querying EV. But for the ICSR form, the different levels of access apply (1, 2a and 3) as per the EV Access Policy.

7. EudraVigilance Organisations Users MAHs 5,476 18,970 NCAs 78* 1,256
16 January 2019
EudraVigilance – Registered Users
EudraVigilance
Organisations
Users
MAHs
5,476
18,970
NCAs
78*
1,256
EVDAS
Organisations
Users
MAHs
2,064
6,277
NCAs
65*
878
* Includes regional centres 7

8. Number of ICSRs processed: 22 November 2017 – 5 March 2018 ICSRs Total
EudraVigilance – Processing of ICSRs
Number of ICSRs processed: 22 November 2017 – 5 March 2018
ICSRs
Total
EEA
Non-EEA
Serious
325,625
142,572
183,053
Non-serious
321,311
315,036
6,275 8

9. EVDAS for signal management Closure
Outline
Introduction
EVWEB for downloading
EVDAS for signal management
Closure

10. ICSR download requests by MAHs: 22 November 2017 – 5 March 2018
EudraVigilance – ICSR download requests by MAHs
ICSR download requests by MAHs: 22 November 2017 – 5 March 2018
1,274 MAHs submitted download request to EV
74,070 download requests successfully executed
5,987,253 ICSRs downloaded 10

11. EudraVigilance - hypercare and maintenance
New filters added to improve download functionalities:
EudraVigilance release notes:
‘Sender organisation’
NCA (EEA Member States) Other sender organisations (excluding NCAs) All sender organisations
‘Current report only’:
exclude ICSRs if a newer version of the case has been subsequently received from the same original Sender
‘Report type’:
“Spontaneous”, “Report from studies”, “Other” or “Not available to sender (unknown)”

12. EudraVigilance - hypercare and maintenance
Fortnightly maintenance releases planned until end May 2018 to include:
Further improve the ICSR download functionality
Adding a print search function (e.g. Excel) that will contain the search parameters and the results (e.g. Worldwide case identifier), including no results
This will allow to:
“Print” the searches for documentation
Get an (Excel) file to document data retrieved with L2A access
“Document none hits” (request launch and retrieved no data)

13. EudraVigilance - hypercare and maintenance
Fortnightly maintenance releases planned until end May 2018 to include:
b. Cancellation of download request
Implement an option for the user to cancel the download request they launched
Additional download format
User will be able to select to EV ICSR downloads in xml and rtf format

14. Processing of ICSRs downloaded from EudraVigilance
Don’t send EEA cases originating from NCAs back to EudraVigilance
without having received new information from the primary source. .
MAH version
NCA case EV
MAH (1-n)
Master
MAH version
MAH version
Master

15. Processing of ICSRs downloaded from EudraVigilance
Don’t send ICSRs back to EV that were submitted by other MAHs
Even if you disagree with the other MAHs assessment
Don’t send back to EV MLM ICSRs
Unless you have contacted the primary source and you have obtained additional first-hand information from them
Don’t send nullifications for ICSRs that were sent to EV by other sender organisations

16. Processing of ICSRs downloaded from EudraVigilance
Don’t send ICSRs back to EV where:
reported suspected adverse reaction ​was upgraded from non-serious to serious
ICSRs downloaded from EudraVigilance should only be resubmitted if the sender organisation has received NEW information from the primary source that qualifies for the submission of a follow-up report.

17. Download of ICSRs
Recommendation to avoid multiple downloads of the same ICSRs (where as possible): Set the end date of L2A downloads to at least 3 days before the last available date indicated on screen

18. with marketing authorisation for paracetamol and ibuprofen
Download of ICSRs
16 January 2019
Example of MAH
with marketing authorisation
for paracetamol and ibuprofen

19. EVDAS for signal management Closure
Outline
Introduction
EVWEB for downloading
EVDAS for signal management
Closure

20. Signal management pilot
Commission Implementing Regulation (EU) No 520/2012 requires MAHs to continuously monitor EV data and inform regulatory authorities of validated signals.
guidance available in GVP IX rev. 1.
template for Stand alone signal notification
To streamline the implementation of these requirements, EMA and the European Commission have agreed on transitional arrangements:
pilot period of one year starting on 22 February 2018,
focussing on limited number of active substances (based on additional monitoring list).

21. Some features of the pilot list (1)

22. Some features of the pilot list (2)

23. Tools for screening EudraVigilance
16 January 2019

24. Handling of EV signals – notify authorities

25. 16 January 2019
Validation of signals
Reasonable efforts should be made to ensure that a signal is really new, i.e. not already addressed in other EU SmPCs (e.g. originator SmPC, agencies’ websites, PROTECT ADR database…) or considered by EMA/PRAC (EMA communications, referrals). For inspiration: See checklist in SCOPE WP5 Signal Management Best Practice Guide

26. What is considered ‘day zero’ for notifying regulatory authorities?
Completion of MAH assessment is ‘Day 0’ of reporting timelines.

27. What are the obligations for substances not on the pilot list?
Is substance on the pilot list?
Obligation to monitor EV
No obligation to monitor EV
Start 22 Feb 2018
yes
Access to EV as additional data source to complement existing signal management activities no
don’t send stand alone signal notifications to EMA/NCAs (i.e. existing processes and procedures should be used)

28. What are the obligations for substances not on the pilot list?
BUT.. use EudraVigilance data for PSURs!
“PSURs shall be based on all available data and therefore EudraVigilance should be used as another source of information”
“whenever there are signals evaluations in the PSUR triggered by other sources of information or there are issues under close monitoring, it is expected that the data from EudraVigilance is considered in order to complement and enhance the signal assessments and the conclusions for issues under close monitoring”
Source: Explanatory Note to GVP Module VII,
EMA/670256/2017, 31Oct2017

29. to present comprehensive signal information in PSURs
How should MAHs report signals not originating from EV data to authorities?
16 January 2019
Signals should be reported to the authorities as usual, taking into account the general obligations of the MAH to:
keep their product information up-to-date throughout the product’s life cycle by Variation applications
to present comprehensive signal information in PSURs
inform authorities of emerging safety issues (ESI)
What authorities DON’t want: a notification stating that a literature article was considered a validated signal - not a signal based on EV data
PSUR
Variation
ESI

30. EVDAS for signal management Closure
Outline
Introduction
EVWEB for downloading
EVDAS for signal management
Closure

31. Million dollar question
MAHs are seeking clarification about their obligations to record suspected adverse reactions they access through EudraVigilance - as part of the downloaded ICSRs via EVWEB - as part of the EVDAS access for signal management
Proposal discussed with Pharmacovigilance Business Team, EudraVigilance Expert Working Group, PRAC and Pharmacovigilance Inspectors Working Group (PhV IWG)

32. Some key principles (1)
The legislation is silent about MAHs obligations as regards the recording of the suspected adverse reactions they become aware of as part of their EudraVigilance access.
The legislation puts specific emphasis on the fact that MAHs should access reports originating from NCAs through EudraVigilance (Directive 2001/83/EC, Article 107a, paragraph 4, 3rd subparagraph).
Duplication of efforts in recording adverse reactions reports should be limited (“simplified reporting”) thus freeing resources to focus on the monitoring of the safety of medicines.

33. Some key principles (2)
The main requirements for recording and reporting suspected adverse reactions in the EU and 3rd countries is based on the fact that the MAH is the “receiver” of the information from the reporter: “MAHs shall record all suspected adverse reactions in the Union or in third countries which are brought to their attention, whether reported spontaneously by patients or healthcare professionals, or occurring in the context of a post-authorisation study”. (DIR 2001/83/EC, Art 107, par 1).
Recording of ICSRs necessary to “comply with pharmacovigilance obligations” refers to the tasks and responsibilities listed in Title IX of Dir 2001/83/EC

34. EMA will issue further guidance following consultation with the EC.
Next steps
EMA will consult the European Commission (EC) on the legal interpretation of the proposal in the context of the EU pharmacovigilance legislation.
EMA will issue further guidance following consultation with the EC.
Industry has been invited to nominate volunteers to work with the EudraVigilance Expert Working Group on the development of criteria to determine “pharmacovigilance obligations” and the subsequent recording of cases.
In the meantime, proceed in accordance with your currently established processes.

35. Please continue to share your - questions - issues - proposals for improvement
EMA EV support page:
Questions & Answers: