The EudraVigilance system, updated in May 2017 and effective from November 22, 2017, enhances the management and analysis of suspected adverse reactions to medicines in the EU. Key changes include improved safety monitoring, streamlined submission processes, and enhanced data analysis capabilities, all aimed at better protecting public health. These updates necessitate organizations to upgrade their processes and IT infrastructure to comply with new reporting and signal management requirements.

1. EudraVigilance:
what’s changed?
In May 2017, the updates to the EudraVigilance system were approved for release and the changes
went into effect on 22 November 2017, implemented by the European Medicines Agency (EMA)
The system is used to manage and analyse
information on suspected adverse reactions to
medicines that need to be reported in the
European Union (EU). It is operated by the EMA
on behalf of the EU medicines regulatory network.
The system itself supports the safe and effective
use of medicines by facilitating the electronic
exchange of individual case safety reports between
the EMA, national competent authorities,
marketing authorisation holders (MAHs) and the
World Health Organisation (WHO). It also
facilitates the early detection and evaluation of
possible safety signals and enables better product
information for medicines authorised in the
European Economic Area (EEA).
This long-anticipated update follows on from
the independent audit of the system completed
earlier in 2017. The recommendations provided by
the Pharmacovigilance Risk Assessment
Committee (PRAC) were favourable, confirming
that the EMA is on track. These revisions will
ensure that the database achieves full
functionality and the system meets the
operational specifications.1
Changes to the system
The revisions to the EudraVigilance (EV) system
look to enable the improved safety monitoring of
medicines. Specifically, they streamline the
submission process and simplify the reporting of
individual case safety reports. This will also
increase the transparency and efficiency of the EV
system to ensure the protection of public health.
The foci of the changes are listed below:
G data submission and collection (EV Gateway,
EVWEB)
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2. G data management (EudraVigilance Database
Management System [EBDMS], recording,
duplicate detection)
G data analysis (EudraVigilance Data Analysis
System, European database of suspected
Adverse Drug Reaction Report [Adrreports.eu]).
Further to this, key changes are also discussed in
the revisions to the Proposed Module VI, which is
coupled with the changes introduced through ICH
E2B (R3).
The updated system will simplify reporting
requirements for individual case safety reports
(ICSRs), which is expected to decrease the time
spent making reporting decisions. The EV system
will also increase collaboration with WHO by
making reports of individual cases of suspected
adverse reactions available to the WHO Uppsala
Monitoring Centre directly from EV. The updates
will also enhance the data analysis capabilities
through the EV Data Analysis System (EVDAS).
Additionally, MAHs will no longer be required to
do country specific registrations and/or testing to
set up organisation identifiers.
The main changes to the electronic reporting
requirements for MAHs include that all reports of
suspected adverse drug reactions (ADRs)
requiring submission according to Regulation (EC)
No. 726/2004 and/or Directive 2001/83/EC should
be reported to EV directly. Previously, the
adoption of EV-only submission was limited to a
small number of countries, but will now apply to
all EU member states. The system will include the
UK, at least until its withdrawal from the EU. The
future inclusion of the UK in EU medicines
regulation will depend on the outcome of the
Brexit negotiations.
MAHs will no longer receive ADR reports
directly from EU national competent authorities,
but will be provided access to these through EV.
MAHs will also no longer need to provide ICSRs to
national competent authorities and must submit
these to the EV system only.
Enhancements for signal management
The signal detection process has been updated in
the new EV system, improving the functionality
and reducing the extant duplication of effort.
MAHs shall monitor the data available in the
system to the extent that they have access to, to
determine whether there are new risks or whether
risks have changed for their medicinal product(s)
and active substances. They must then inform the
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28 manufacturing chemist January 2018
EMA and national competent authorities about
safety signals validated to contain sufficient
evidence to necessitate further analysis.
The new updates will allow MAHs access to a
greater level of detail on applicable ICSRs than is
currently supplied. Further details on the process
will be provided in the revised good
pharmacovigilance practices (GVP) Module IX —
signal management. The EMA will also grant
MAHs access to EVDAS to use signal detection,
analytical and reporting functions to the extent
necessary to fulfil their obligation.
The frequency of signal detection activities will
depend on the nature of the product, but
justification for the approaches taken should be
captured in signal management documentation. For
newly licensed products, there is an expected
2-week review cycle; for older, long-marketed
products, this may be reduced to 6 monthly reviews.
MAHs will have the option to create standard
searches and the ability to save customised searches
within the system; however, depending on the
nature of the product and the number of events,
this activity could be resource intensive.
The burden of reporting for suspected non-
serious adverse reactions has been increased, with
organisations now required to report suspected
non-serious adverse reactions to EV within 90
days. Before this update, only seven EEA national
competent authorities required non-serious case
reporting. The burden will vary by product and
therefore per company, inevitably demanding extra
resources for submissions. The increased reporting
requirements will be supported by the enhanced
performance and scalability of the EV system.
Some elements of the system will remain
unchanged, including the reporting of adverse
reactions by patients and healthcare providers
(HCPs) to national competent authorities based on
local spontaneous reporting systems. The
reporting of suspected unexpected serious adverse
reactions during clinical trials will also remain
unchanged until the application of the new
Clinical Trial Regulation, expected in 2018.
Impact on users
Users of the EV system, including MAHs and
national competent authorities, will need to
ensure their processes and IT infrastructure are
revised in line with the new changes and the
simplified reporting, as outlined in the
revised change management plan.2
Processes must also be developed and
updated to report non-serious cases.
This includes any guidance
documents, safety
“The updated
system will
simplify
reporting
requirements
for individual
case safety
reports, which is
expected to
decrease the
time spent
making
reporting
decisions

3. REGULATORYAFFAIRS
January 2018 manufacturing chemist 29
agreements between licensing partners (SDEAs),
communication plans and safety databases. Since
the original draft ruling in May 2017, the EMA
and European Commission have updated this
process to determine some transitional
agreements to streamline the implementation of
this new process. This means that MAHs have a
grace period until February 2018 to implement
monitoring practices.3
To bring about these changes, it’s important
that teams are trained in accordance with the new
guidelines, through training offered by the EMA
or by taking help from an outsourcing supplier
that’s experienced in this area. The EMA has
noted that it will provide functionality support to
the national competent authorities and MAHs in
the EEA through e-learning, face-to-face training,
webinars and information days.4
Along with this,
any existing users of the system will be
automatically migrated to the new version. More
specifically, training should cover
G use of the new ICH E2B(R3) format
G EVDAS (EudraVigilance Data Analysis
System)
G GVP Module VI (revision 2)
G GVP Module IX (revision 1)
G EudraVigilance access policy.
The new ICH E2B(R3) format can be used for the
electronic exchange of ADRs, improving data
quality. The new format will eventually replace
the current ICH E2B(R2). One notable change in
the new R3 format is that seriousness is reported
at event level rather than only at case level.
Technology changes will be necessary to ensure
systems are compatible with the new database and
formats. When possible, the local gateway should
be configured to support ICH E2B(R3) messages.
MAHs can continue to submit ICSRs in E2B(R2)
format; however, any cases downloaded from
EudraVigilance will be in E2B(R3) format only.
In the interim period, a backwards/forwards
conversion tool will need to be implemented if the
ICH E2B(R3) format cannot be processed locally.
Currently, the deadline for upgrading to a fully
compliant ICH E2B(R3) system has not been
publicised and is expected to be at least 2 years
away. MAHs are advised to work with safety
database providers to ensure ICH E2B(R3)
compatibility.
An important aspect to note from the draft
guidelines is that the EMA views that a “loss of
data, for example, owing to server
breakdown” constitutes a “serious breach”
of regulation. Therefore, sponsors
and vendors are expected to have
IT measures in place to be
FOR MORE
INFORMATION
David Balderson
Global Vice President
Global Safety Operations
Prashant Joshi
Director
Domain and Process, Safety
and Risk Management
Sciformix Corporation
www.sciformix.com
able to retrieve relevant information in the
instance that a system breaks down at any point
in time. To comply with their pharmacovigilance
obligations, it is important that MAHs have the
right access to EudraVigilance. Access is granted
on the basis of the product data supplied by the
EMA in accordance with Article 57(2) of
regulation (EU) No. 726/2004. Therefore, it is
essential that MAHs ensure that the data in the
Article 57 database is always complete and
up-to-date.
Moving forward
These changes look to greatly improve the
functionality of the EV system to ensure public
health is protected to the highest degree.
Resulting from these revisions, organisations and
MAHs have a considerable number of changes to
implement across both processes and their
technology infrastructure. The development of an
internal communications plan to inform all
relevant stakeholders of the change requirements
should be considered.
The priority of MAHs should be to update all
operating procedures for the reporting and
retrieval of ICSRs, along with signal detection
procedures to ensure they are in line with the new
guidelines. The latest update to GVP Module VI
will come into effect within 6 months of the new
EudraVigilance system being released and will
provide further guidance and clarification.
Implementing the required changes could be
resource intensive, with experienced employees
needed to train staff. Preparation is key to
remaining fully compliant after the transition to
the new EudraVigilance database. Working with a
specialised service provider with expertise in
pharmacovigilance, technology infrastructure and
the regulatory requirements will ease the pressure
on organisations and make the move to the new
system as seamless as possible.
REFERENCES
1. www.ema.europa.eu/docs/en_GB/document_library/
Other/2017/05/WC500228158.pdf.
2. www.ema.europa.eu/docs/en_GB/document_library/
Regulatory_and_procedural_guideline/2015/10/
WC500196029.pdf.
3. www.ema.europa.eu/ema/index.jsp?curl=pages/
regulation/general/general_content_000587.jsp&mid=WC0b0
1ac0580727d1b.
4. www.worldpharmanews.com/ema/3952-green-light-given-
for-new-eudravigilance-system-for-collection-and-monitoring-of
-suspected-adverse-reactions.