Signal management & Eudravigilance

Laura Sottosanti

10/07/2018
Public Declaration of transparency/interests*
The view and opinions expressed are those of the individual presenter and should not be attributed
to AIFA
From 0 to 3
Interests in pharmaceutical industry NO Current Over 3 preavious years
previous years
DIRECT INTERESTS:
1.1 Employment with a company: pharmaceutical
X mandatory
company in an executive role
1.2 Employment with a company: in a lead role in the
X mandatory
development of a medicinal product
1.3 Employment with a company: other activities X optional

2. Consultancy for a company X optional

3. Strategic advisory role for a company X optional

4. Financial interests X optional

5. Ownership of a patent X optional

INDIRECT INTERESTS:
6. Principal investigator X optional

7. Investigator X optional

8. Grant or other funding X optional

9. Family members interests X optional

*Laura Sottosanti, in accordance with the Conflict of Interest Regulations approved by AIFA Board of Directors (25.03.2015) and published
on the Official Journal of 15.05.2015 according to EMA policy /626261/2014 on the handling of the conflicts of interest for scientific
committee members and experts.
 Learning objectives
By the end of this session you should have a general understanding of
the:

1. Signal definition
2. GVP module IX and signal process
3. Roles and responsibilities within the EU signal management process
4. Signal management in AIFA
5. Standalone signal notification
6. Emerging Safety Issue
7. Eudravigilance (EV) and Eudravigilance Access Policy
8. Use of EV data and eRMR (electronic Reaction Monitoring Report)
Documents

• Guidance and Legal Requirements

Commission Implementing Regulation (EU) No 520/2012

Directive 2010/84/EU

Good Pharmacovigilance Practices Module IX revision 1

Addendum of GVP IX with new methodology for Signal

detection

Guideline on screening ADRs in EudraVigilance

User Manuals on how to use the tool in signal detection

(EMA, NCAs, MAH)

EMA Question & Answers on Signal Management

 • What’s a Signal?
• Signal is an information that arises from one or multiple sources
(including observations and experiments), which suggests a new
potentially causal association, or a new aspect of a known association,
between an intervention and an event or set of related event, either
adverse or beneficial, that is judged to be of sufficient likelihood to
justify verificatory action.

Report of the Council for International Organisations of

Medical Sciences WG VIII, Practical Aspects of Signal
Detection in Pharmacovigilance (CIOMS, Geneva 2010).
 Signals

Signals are generated from several sources, such as spontaneous

reports of suspected adverse reactions, clinical studies and the
scientific literature.

The evaluation of safety signals is a routine activity within

pharmacovigilance to establish whether or not there is a causal
relationship between the medicine and the reported adverse event.
In cases where a causal relationship is confirmed or considered
likely, regulatory action may be necessary.

*EMA’s Annual Report 2015

 Signal Management Process

• A set of activities performed to determine whether, based on an

examination of
• individual case safety reports (ICSRs),
• aggregated data from active surveillance systems or studies,
• scientific literature information
• or other data sources,
• there are new risks associated with an active substance or a medicinal
product or whether known risks have changed, as well as any related
recommendations, decisions, communications and tracking.
 Signal Management Process

• The EU signal management process includes the following activities:

 Signal detection
The act of looking for and/or identifying signals using data from any source

Detection of safety signals may be performed based on:

 from statistical analyses in large databases,
 a review of individual case safety reports (ICSRs),
 or from a combination of both.

Detection of signals by
monitoring new and
historical data in
EudraVilance
 Statistical criteria to generate a signal
Thresholds defining a signal of disproportionate reporting (SDR) in EudraVigilance

• ROR(-) > 1
• At least 3 cases (AM) or 5 cases (RM)
 PRR and ROR
The PRR is defined as the ratio between the frequency with which a specific
adverse event is reported for the drug of interest (relative to all adverse events
reported for the drug) and the frequency with which the same adverse event is
reported for all drugs in the comparison group (relative to all adverse events
for drugs in the comparison group)

Drug
ADR DataBase

a
c b
d
 An example

ADR1 Other ADRs Tot

Farmaco-A 15 85 100

Other Drugs 5000 95000 100000

Totale 5015 95085 100100

ROR= (15*95000)/(5000*85) = 3,3

 Signal validation

• The process of evaluating the data supporting a detected signal in order

to verify that the available documentation contains sufficient evidence to
justify further analysis of the signal

• This evaluation should take into account the strength of the evidence, the
clinical relevance and the previous awareness of the association

Evidence Based Methods

Clinical

Statistical
Review of individual case safety reports should consider
 strength of evidence for a causal  the suspected medicinal product (e.g.
effect (e.g. number of reports after dose administered) and adverse
exclusion of duplicates and reaction (e.g. signs and symptoms),
inadequately documented cases),
 the reporter’s evaluation of causality
 temporal association, and the plausibility of a biological and
pharmacological relationship
 plausible mechanism,
 Seriousness and severity of the
 de/re-challenge (the clinical outcome
reaction and its outcome;
in relation to drug continuation or
discontinuation),  novelty of the reaction (e.g. new and
serious adverse reactions);
 alternative explanation/confounders;
 Drug-drug interaction
 the patient’s demographics (e.g. age  exposure
and sex), Reactions occurring in
special populations
Review of individual case safety reports should consider
…And also
 information is already included in the SmPC or patient leaflet;
 the association has already been assessed in the PSUR or RMP, or was discussed
at the level of a scientific committee or has been subject to a regulatory
procedure
 literature findings regarding similar cases
 experimental findings or biological mechanisms
The detection of signals shall be based on a
multidisciplinary approach

Guideline on good pharmacovigilance practices (GVP)

Module IX – Signal management
 Signal validation

• Validated signal: A signal for which the signal validation process has
verified that the available documentation contains sufficient evidence
demonstrating the existence of a new potentially causal association, or a
new aspect of a known association, and therefore justifies further
analysis of the signal.

• Non-validated signal: A signal for which the signal validation process has
led to the conclusion that the available documentation at that point in
time does not contain sufficient evidence demonstrating the existence of
a new potentially causal association, or a new aspect of a known
association, and that therefore further analysis of the signal is not
warranted.
 Tracking
All signals validated should be recorded and tracked systematically for each
step: detection, validation, confirmation, prioritisation, assessment,
timelines, decisions, actions, etc..
 Signal confirmation

• The process during which the competent authority of a Member State

(where the signal concerns a medicinal product authorised in accordance
with DIR), or the Rapporteur appointed by the Pharmacovigilance Risk
Assessment Committee (PRAC) (where the signal concerns a product
authorised in accordance with REG), decides whether or not a validated
signal should be analysed and prioritised by the PRAC.

• This should be done within 30 days from receipt of the validated signal.

• Signal confirmation is not intended to be a full assessment of the signal.

The fact that a signal is confirmed does not imply that a causal relationship
has been established, but that the signal should be discussed at EU level
and further investigated by PRAC
 Signal analysis and prioritisation by the PRAC

• The process by which the PRAC determines whether a confirmed signal

requires further evaluation, and if required, to what timeframe and in
which procedural framework.

• This is based on an initial analysis of the potential impact of the signal

on patient and public health and the risk-benefit balance of the
concerned medicinal product(s)
 Signal analysis and prioritisation by the PRAC

When prioritising signals, the PRAC may take into account several factors,
including:
 any potential impact on the benefit-risk profile of the product,
 strength of evidence supporting a causal association,
 severity and seriousness of the reaction
 estimated frequency of occurrence,
 preventability, the consequences of discontinuing treatment
 the availability of alternative therapeutic options,
 extent of utilisation of the medicinal product in the general population or in
particular patient groups,
 complexity of the issue
 the expected volume of data.
 Signal analysis and prioritisation

• A key element of the signal management process is to promptly

identify signals with important public health impact or that may affect
the benefit-risk balance of the medicinal product in treated patients.

• Which signals require urgent attention and need to be evaluated

without delay.
 Signal analysis and prioritisation by the PRAC

• When the PRAC requests additional data from MAHs, these timelines
usually encompass 2 months for submission of responses by the MAHs
and 60 days for assessment by the PRAC.

• However where appropriate, shorter or longer timelines may apply.

 Signal assessment by the PRAC

• Following PRAC initial analysis and prioritisation, the process of

evaluating all available data relevant to a signal to determine the need
for any regulatory action
PRAC recommendations for action
 PRAC recommendations for update PI
PRAC recommendations for update of the product information following assessment
of a signal usually include the wording to be implemented in the summary of
product characteristics (SmPC) and/or package leaflet (PL) as well as the timeline
for submission of the variation

The implementation of the published wording and translations can generally be

handled through a type IAIN variation.

PRAC recommendations to update the product information are applicable to all

medicinal products containing the concerned substance, unless otherwise specified

MAHs are expected to submit the requested variation according to the timeline
specified in the PRAC recommendation. This timeline is calculated from the date of
publication of the PRAC recommendation. For instance, recommendations for update
of the product information adopted by PRAC in September 2014 were expected to
be submitted within 1 or 2 months of 30 September 2014 (publication date), as
applicable.
 Signal Management Process

• The EU signal management process includes the following activities:

 Roles and responsibilities within the EU signal
management process
The continuous monitoring of EudraVigilance is a legal requirement in the EU

All Member States shall be responsible for monitoring the data in the
EudraVigilance database

Within the EU regulatory network, the Agency takes the lead for EudraVigilance
monitoring, signal detection and signal validation for active substances contained in
at least one centrally authorised product. Signals validated by the Agency should be
confirmed (or not) by the PRAC rapporteur for the concerned centrally authorised
product.

For active substances only contained in nationally authorised products, Member

States take the lead (Lead Member State) for EudraVigilance monitoring, signal
detection, validation and confirmation.
 Roles and responsibilities within the EU signal
management process
• Lead Member State for signal management: The Member State responsible
for monitoring the EudraVigilance database for an active substance or
combination of active substances contained in medicinal products authorised
in more than one Member State through the national, mutual recognition or
decentralised procedures. The lead Member State shall validate and confirm
signals on behalf of the other Member States

• If the active substance is authorised in only one Member State, that Member
State automatically assumes the responsibilities of the Lead Member State.
 Roles and responsibilities within the EU signal
management process
• PRAC Rapporteur: Rapporteur appointed by the PRAC in the context of
the centralised procedure. Within the EU signal management process,
the PRAC Rapporteur is responsible for the confirmation of signals
concerning centrally authorised medicinal products.

• Signal confirmation by the PRAC Rapporteur or (lead) Member State:

The process of deciding whether or not a validated signal entered in
the European Pharmacovigilance Issues Tracking Tool (EPITT) requires
further analysis and prioritisation by the PRAC.
This should be done by the PRAC Rapporteur or the (lead) Member
State within 30 days from receipt of the validated signal.
Roles and responsibilities within the EU signal
management process
European signal process
 ABSENCE OF EVIDENCE IS NOT EVIDENCE OF
ABSENCE

If no signal is produced at the end of the analysis it is not

possible to tell whether this is because the signal does not exist
or because insufficient data are being analysed

33
 Signal Management by MAHs
Commission Implementing Regulation (EU) No 520/2012 (article 18)
requires EMA, national competent authorities and marketing authorisation
holders (MAHs) to continuously monitor the data available in
EudraVigilance.

22 February 2018 Signal Detection in EVDAS by MAH:

Transitional arrangements for MAHs
 Pilot period of 1year
 MAHs of the active substances included in the
additional monitoring list
 Three-month 'grace period‘ to familiarise
 Monitoring EV – Signal Management

 All other MAHs also have access to EudraVigilance data and can integrate the
data into their own signal management processes. However, during the pilot
period they will have no obligation to continuously monitor EudraVigilance
and inform the regulatory authorities of validated signals.

 After one year, EMA will base the next phase of implementation on
experience gained through the pilot.

 It also requires MAHs to inform EMA and national competent authorities of

validated signals detected when monitoring the database.
 Standalone signal notification

Within 30 days of receipt of a signal validated by the Agency or a

Member State, or a standalone signal notification from a marketing
authorisation holder, the PRAC rapporteur or (lead) Member State, as
applicable, should confirm or not the signal.
 Emerging Safety Issue

• A safety issue considered by a marketing authorisation holder to

require urgent attention by the competent authority because of the
potential major impact on the risk-benefit balance of the medicinal
product and/or on patients’ or public health and the potential need
for prompt regulatory action and communication to patients and
healthcare professionals.

• An ESI is in addition to the ICSR submission requirements, when the

emerging safety issue refers to a single case of suspected adverse
reactions
 Emerging Safety Issue

• When the MAH in the EU becomes aware of an emerging safety

issue from any source, they should notify it in writing to the
competent authority(ies) of Member State(s) where the medicinal
product is authorised and to the Agency to the mailbox P-PV-
[email protected]”.

• This should be done as soon as possible and no later than 3 working

days after establishing that a validated signal or a safety issue from
any source meets the definition of an emerging safety issue.

• For AIFA: [email protected]

 Emerging Safety Issue

MAHs

as soon as possible and no later than 3 working days

 Agency to the mailbox

[email protected]

 Competent authority(ies) of MSs where the medicinal

product is authorised
(AIFA to the mailbox [email protected])
 Emerging Safety Issue

• When notifying an emerging safety issue, the marketing

authorisation holder should describe the safety issue, the source(s)
of information, any planned or taken actions with timelines, and
should provide any relevant documentation available at the time of
initial notification.

• Upon being notified of an emerging safety issue, the national

competent authorities and/or the Agency as appropriate should
promptly assess the urgency and potential impact of the issue and
agree on appropriate next steps and the potential regulatory
procedure to address the matter raised. This may involve the
consultation of the Incident Review Network, if warranted
 Emerging Safety Issue and possible actions

Should the MAH decide as a result of the emerging safety issue to take
any of the following actions:

• temporary or permanent cessation or suspension of marketing of a

medicinal product,
• withdrawal of a medicinal product from the market,
• request for the withdrawal of a marketing authorisation
• or non-application for the renewal of a marketing authorisation,
 Signals
The safety information contained in EudraVigilance is continuously screened
using statistical reports called electronic Reaction Monitoring Reports
(eRMRs). In 2017, a total of 21,496 such outputs were produced and
provided to the EU network for review.

– NAP: Lead member State

– CAP: EMA & PRAC Rapporteur (of 2,062 potential signals which were
reviewed by the Agency in 2017, around 82% originated from
EudraVigilance, highlighting its central role for ADR data monitoring).

electronic
Reaction Monitoring Reports
(eRMR)
 Signals

In 2017, the PRAC assessed 82

signals of new or changing safety
issues and about two thirds of these
were detected in full or part from
EudraVigilance.
 eRMR

 The eRMR is a tool to perform signal detection in EV.

 This tool provides aggregated data related to the ICSRs

submitted to EudraVigilance stratified by different parameters
and incorporates the Reporting Odds Ratio (ROR) as a
statistical measure.

 Valid cases transmitted to the EVPM module only (ICSRs

transmitted retrospectively to EVPM)

 Identified duplicates are excluded by default

eRMR for screening EudraVigilance

eRMR for screening EudraVigilance

Tools Used in Signal Detection

Electronic Reaction Monitoring Report (eRMR) is

a formatted Excel file used as a tool for
monitoring the safety of drug use, facilitating
prioritisation, detection, evaluation and
documentation of suspected adverse drug
reactions (ADR) in EudraVigilance EV

• Manage the workload

• Early identification of very serious ADRs
45
eRMR – structure and content
eRMR
 How to select the eRMR
• Column “Changes”: to display only the DECs received during the period of
interest, in the column ‘Changes’ filter out the ‘Blanks’ option:
Clinical Methods

Clinical Methods

Designated Medical Targeted Medical

Events (DMEs) events (TMEs)
• Events known to arise in • The TMEs are ADRs more
causal association with frequently associated with a
medicinal products more serious outcome in
children

Fatal Events
1. Events reported with a
fatal outcome
2. May have strong impact
on public health
PRIORITISATION in the TOTAL Population

1. (DMEs)

2. SDR - IME (not DME) by subgroups

3. All remaining events with a fatal outcome

 SDR
ROR (-)
All
ROR (-)
Rest Relative Paed Relative Geriatr
Priority Geriatr

ROR (-) Ratio (-) Ratio (-)

Priority Paed

Japan
Priority all

ROR (-) Tot Paed Cases Tot Geria Cases

Asia
ROR (-)
Nor.Amer New Paed Cases New Geria Cases
ROR (-)
Europe
1.IME
2.IME

-SDR
1.TME

-SDR

Tot Sp. Cases

New Sp. Cases
3.Fatal
2.IME-
1.DME

SDR
Flagging Priorities

 Priorities Paediatrics

 Priorities Geriatrics
 Priorities Total
population
 Additional useful information

 Positive Re-challenge

 Literature Reports

 Most reported Route of

Administration (RoA)

 Most reported Indicat. (HLGT)

 Abuse Misuse Overdose Med.Error Occ.Exposure
AMOMO
Rational

New

Total

New Occupational Exposure

Total Occupational Exposure

Total Abuse-Misuse-Overdose
New Abuse-Misuse-Overdose
 No imposed prioritisation: they are a +--
contributory factor in the assessment

Medication Error

Medication Error
++-
 Enhanced visual presentation in the
eRMR
--+
 No statistical detection of risk related to
AMOMO (no SDR) but view in
conjunction with a potential ADR
 Signal Status and Comments
Signal
Status
Comments

Most relevant columns of the eRMR Listed SmPC 4.8/4.4

which allow interaction with the Synonymous or related
Validators for tracking reviews and Linked medical concept
previous awareness.
Validated Signal Entered in EPITT
The labels used to assigned the signal
status are provided in a drop-list and PSUR/RMP Signal Assessed in PSUR
in the legend worksheet.
Disease Indication/Symptoms

Other Review unlikely useful

Closed Alternative explanations

Ongoing Signal under review

Monitor Signal under monitoring

Check Case review warranted

 In AIFA 2 signal management processes in
cooperation with Regional Pharmacovigilance Centers

All national data* All Eudravigilance data

(Rete Nazionale di FV)

 For all substances  Only on some substances (153 con

 Every 6 months IT LMS)
 26 substances every month
 69 substances every 3 months
 58 substances every 6months

* The competent authority

of each Member State
shall be responsible for
monitoring the data
originating in the territory
of that Member State
 Signal Management Process and Quality System

We have two different Standard Operative Procedures

• SOP 067 - Gestione dei segnali dalla Rete Nazionale di

Farmacovigilanza

• SOP 401 - Signal Management in Eudravigilance

The activity of signal management in AIFA is carried
out in collaboration with Regional Pharmacovigilance
Centers

AIFA

CRFV CRFV CRFV CRFV CRFV CRFV CRFV CRFV CRFV CRFV

The activity is organized by category ATC

 D.M. 30.04.2015 - Farmacovigilanza,
procedure operative e soluzioni tecniche

Signal detection

CRF
V
AIFA
 Categoria ATC CRFV
M - Musculoskeletal system Lombardia -
B - Blood and blood forming organs Piemonte
C - Cardiovascular system E Romagna -
Calabria - Puglia
J - Antiinfectives for systemic use Sicilia - Veneto
S - Sensory organs
V- Various ATC structures
L - Antineoplastic and immunomodulating agents Toscana - Lazio –
Umbria – Abruzzo

A - Alimentary tract and metabolisma Veneto - Friuli VG - PA

H - Systemic hormonal preparations, excluding reproductive Bolzano
hormones and insulins

N - Nervous system Campania - Molise -

P - Antiparasitic products, insecticides and repellents Sardegna

R - Respiratory system Liguria -

Valle D’Aosta
D - Dermatological drugs Basilicata - Marche
G - Genitourinary system and reproductive hormones Lazio – Umbria
 Signal management process in AIFA
STEP 1 – the eRMR files are generated by EMA and saved in the European Medicines
Agency Meeting documents system (MMD). One eRMR for each substance

STEP 2 – the eRMR files (with Italy as LMS) are downloaded by AIFA signal coordinator
and saved in a common area of the Office

STEP 3 - the eRMR files are updated with the results of previous evaluations and
forwarded by AIFA to all Regional PhV Centers (an e-mail is sent to CRFVs by the AIFA
signal coordinator)

STEP 4 – the CRFV carry out the screening of eRMR following the priority and statistical
criteria. In the eRMR the CRFV fill the “signal status field” with their evaluation and
comments. At the end of this activity the CRFVs generate the files “comments” for each
eRMR
 Signal management process in AIFA
STEP 5 – The “comments “ containing the results of screening by the CRFV are sent to
AIFA

STEP 6 – AIFA carry out the review of ICSRs in Eudravigilance for each drug-event
combination flagged with “check” by CRFV.

STEP 7 – for potential signal the review of literatureit is requested to CRFV

STEP 8 - if the signal is validated, AIFA and CRFV cooperate to prepare the signal AR to
upload in EPITT
 Signal management process in AIFA

• CRFV:
– Screening eRMR (statistical criteria)
– Literature review
– Check RCP (ADR is listed or unlisted)
– Review of cases in national database

• AIFA:
– Review of cases in Eudravigilance and signal validation

• AIFA + CRFV:
– Signal Assessment Report (signal description (including
recommended actions and summary of the relevant case
narratives))
The new EudraVigilance System
 Data Origins

(xEVMPD)

64
 Data Origins

The data stored in the EV Data Warehouse (EV DWH) carry the same
information as the ones stored in the Source Systems.

There is a procedure called EudraVigilance ETL that:

 Extracts the data from the source systems,

 Transforms the data in order to structure the information in a way
more useful to the data analysis, &
 Loads the re-structured data in the EV DWH

65
 ETL process
The extraction, transfer, and loading (ETL) process is the means by which
data are transferred from source systems and loaded into the EudraVigilance
Data Warehouse. Specifically, the ETL process does the following:

• Stores information about the structure and contents of source systems and
the Data Warehouse;
• Correlates the source systems structure and contents to the structure and
contents of the Data Warehouse;
• Provides information to the data extraction tools that physically execute
the transfer of data from source systems to the Data Warehouse.

!! The ETL process is performed NIGHTLY so that every day the

EudraVigilance Data Warehouse is populated with data updated to the
day before
 The new and improved EudraVigilance
to simplify reporting and data analysis

On 22 November 2017, EMA launched the new and improved version of

EudraVigilance, the European database and analytical system that holds
reports of suspected adverse reactions to human medicines that are
authorised or being studied in clinical trials in the European Economic Area.
 The enhancements and expected benefts of the new
EudraVigilance are:

 simplifed reporting of ICSR and reduced duplication of efforts. Marketing

authorisation holders now report directly to EudraVigilance rather than
individual NCAs, who instead access the ICSRs from EudraVigilance;

 better detection of new or changing safety issues, enabling rapid action

by regulators to protect public health;

 better searchability and more efficient data analysis based on the use of
the ISO/ICH agreed standard for ICSRs and new query functions;
The enhancements and expected benefts of the new
EudraVigilance are:

 increased system capacity to support large volumes of users and reports;

 greater transparency in safety monitoring and much greater access to data

and information for patients and healthcare professionals (adrreports.eu);

 more efficient collaboration with the WHO, with EMA making all ICSRs
originating in the EEA directly available from EudraVigilance to the WHO
Uppsala Monitoring Centre (UMC).

More safety
More patient
monitoring of
safety
medicines
 Rerouting for NCAs
 NCAs are able to update the rerouting parameters at any time
 Automatic forwarding of ICSRs to the applicable NCA in a Member State
 ICH E2B(R3) format (ICSRs are rerouted in the format received i.e. no
conversions between ICH E2B(R2) and ICH E2B(R3) is applied)

Rerouting parameters
for Italy
 Recoding process

• The rerouting of ICSRs with recoded medicinal product information will

be put in place following implementation of the ISO IDMP terminologies

• The current recoding process is only for use by EMA.

• XEVMPD is used to support recoding of medicinal product information in
ICSRs until ISO IDMP terminologies are available and implemented
 Download for MAHs

 MAHs no longer have to receive ICSRs directly from NCAs

 A download function is available to MAHs to obtain access to these ICSRs

 MAHs are able to download ICSRs for active substances of medicinal

products, for which the MAHs hold a marketing authorisation in the EEA

 Access to ICSRs is based on the medicinal product information submitted by

MAHs to the XEVMPD (Article 57 product submissions) (Access Level 2A of the
revised EudraVigilance Access Policy)

 ICSRs are made available in ICH E2B(R3) format only

 New Business Rules

22 November 2017
 Eudravigilance Access Policy – Rev 2
 MAH access to the EV system
 GVP Module VI – Rev 2
 Simplified Electronic Reporting
 GVP Module IX – Rev 1
Simplified reporting of suspected adverse
reactions in the EU - NCAs
Simplified reporting of suspected adverse
reactions in the EU – WHO-UMC
Simplified reporting of suspected adverse
reactions in the EU - MAHs
Simplified reporting of suspected adverse
reactions in the EU - MAHs
 Il Sistema di segnalazione italiano

vigifarmaco

RPhV
7 days

RPhV RNF MAHs

7 days 15/90 days
RE-ROUTING
DOWNLOAD
RPhV/CRFV
MAHs
 The Eudravigilance Database

7
9
The Eudravigilance Database Management System
The Eudravigilance Data Analysis System
[email protected]