PHARMACOVIGILANCE

INTERVIEW
FREQUENTLY ASKED
QUESTIONS &
ANSWERS

Best for Excellent for

Freshers Experienced PV
Professionals

By PV & Drug Safety Team

 Purpose of this eBook

Hello Readers,
The purpose of this eBook is to
help freshers and experienced PV
professionals in their interview
preparaton.

As Pharmacovigilance (PV) is very

broad field, we cannot cover each
and every aspects of PV in this
eBook. However, this eBook will be
helpful to understand basic
concepts of PV and for revision
purpose during interview time.

Your suggestions and opinions are

welcome. We may consider your
suggestions and would incorporate
in future edition.
 Index

This eBook contains

information on following topics:

PV Abbreviations......................page 04
PV Basics and ICSR..................page 10
Special situation scenarios.....page 32
MedDRA......................................page 40
Aggregate reporting.................page 44
Signal Management.................page 58
Risk Management.....................page 66
EudraVigilance..........................page 77
Labelling......................................page 80
PSMF............................................page 86
Vaccine pharmacovigilance...page 90
PV Agreements..........................page 94
Pharmacovigilance
Abbreviations
ADR: Adverse Drug Reaction
AE: Adverse Event
AEFI: Adverse event following
immunization
AESI: Adverse event of special interest
aRMM: Additional risk minimisation
measure
ATMP: Advanced therapy medicinal
product
CCDS: Company core data sheet
CCSI: Company core safety information
CHMP: Committee for Medicinal
Products for Human Use
CIOMS: Council for International
Organizations of Medical Sciences
CMDh: Coordination Group for Mutual
Recognition and Decentralised
Procedures – Human
DDPS: Detailed description of the
pharmacovigilance system
DEC: Drug Event Combination
DHPC: Direct healthcare professional
communication
DIBD: Development international birth
date
DLP: Data lock point
DME: Designated Medical Event
DSUR: Development Safety Update
Report
eCTD: Electronic common technical
document
eRMR: Electronic Reaction Monitoring
Report
EEA: European Economic Area
EMA: European Medicines Agency
EPAR: European public assessment
report
EPITT: European Pharmacovigilance
Issues Tracking Tool
eRMR: Electronic reaction monitoring
report
EU: European Union
EudraCT: European Clinical Trials
Database
EuRD: EU reference date
EV: EudraVigilance
EVCTM: EudraVigilance Clinical Trial
Module
EVDAS: EudraVigilance Data Analysis
System
EV EWG: EudraVigilance Expert Working
Group
EVMPD: EudraVigilance Medicinal Product
Dictionary
EVPM: EudraVigilance Post-Authorisation
Module
EVWEB: EudraVigilance Web application
FAERS: FDA Adverse Event Reporting
System
GCP: Good clinical practice
GVP: Good pharmacovigilance practices
HLGT: Higher level group term
HLT: High-level term
IBD: International Birth Date
ICH: The International Conference on
Harmonization of Technical Requirements
for Registration of Pharmaceuticals for
Human Use
ICSR: Individual Case Safety Report
IME: Important medical event
INN: International non-proprietary name
MA: Marketing authorisation
MAH: Marketing authorisation holder
ME: Medication error
MedDRA: Medical Dictionary for Regulatory
Activities
MLM: Medical Literature Monitoring
NCA: National competent authority
PAES: Post-authorisation efficacy study
PASS: Post-authorisation safety study
PBRER: Periodic benefit-risk evaluation
report
PhV: Pharmacovigilance
PL: Package leaflet
PPP: Pregnancy prevention programme
PRAC: Pharmacovigilance and Risk
Assessment Committee
PRR: Proportional reporting ratio
PSMF: Pharmacovigilance system master
file
PSUR: Periodic safety update report
PT: Preferred term
QPPV: Qualified Person responsible for
Pharmacovigilance
RCT: Randomised clinical trial
RMM: Risk minimisation measure
RMP: Risk management plan
ROR: Reporting Odds Ratio
SAE: Serious Adverse Event
SAR: Serious Adverse Reaction
SDR: Signal of disproportionate reporting
SmPC: Summary of product characteristics
SMQ: Standardised MedDRA query
SOC: System organ class
SUSAR: Suspected Unexpected Serious
Adverse Reaction
USFDA: United States Food & Drug
Administration
WHO: World Health Organization
WHO DD: WHO Drug Dictionary
xEVMPD: eXtended EudraVigilance
Medicinal Product Dictionary
Pharmacovigilance
Basics & ICSR
What is Pharmacovigilance?
The World Health Organization (WHO) has
defined Pharmacovigilance as “science and
activities relating to the detection, assessment,
understanding and prevention of adverse
effects or any other medicine-related problem.

What are main objectives of

Pharmacovigilance?
Pharmacovigilance covers the entire life-cycle
of a medicinal product.
Underlying objectives of pharmacovigilance are:
Preventing harm from adverse reactions in
humans arising from the use of authorised
medicinal products within or outside the
terms of marketing authorisation or from
occupational exposure; and
Promoting the safe and effective use of
medicinal products, in particular through
providing timely information about the
safety of medicinal products to patients,
healthcare professionals, and the public.
It is an activity contributing to the
protection of patient’s and public health.
What is the minimum criteria required
for a valid case?
The following 4 minimum criteria is required
to become a case valid.
An identifiable reporter
An identifiable patient
A suspect product
An adverse drug event

What is an Adverse Event (AE)?

Any untoward medical occurrence in a patient
or clinical investigation subject administered a
pharmaceutical product, and which does not
necessarily have to have a causal relationship
with this treatment or any unfavorable and
unintended sign (including an abnormal
laboratory finding, for example), symptom, or
disease temporally associated with the use of
a medicinal product, whether or not
considered related to the medicinal product.
What is an Adverse Drug Reaction (ADR)?
A response to a medicinal product which is
noxious and unintended. Response in this
context means that a causal relationship
between a medicinal product and an adverse
event is at least a reasonable possibility.
Adverse reactions may arise from use of the
product within or outside the terms of the
marketing authorisation or from occupational
exposure. Conditions of use outside the
marketing authorisation include off-label use,
overdose, misuse, abuse, and medication
errors.

What is side effect?

In medicine, a side effect is an effect, whether
therapeutic or adverse, that is secondary to the
one intended; although the term is
predominantly employed to describe adverse
effects, it can also apply to beneficial, but
unintended, consequences of the use of a
drug.
Side effects may vary for each individual
depending on the person's disease state, age,
weight, gender, ethnicity and general health.
What is the difference between an
Adverse Event (AE) and Adverse Drug
Reaction (ADR)?
There may not be a causal relationship
between a drug and an adverse event,
whereas, there is an always causal association
between a drug and an adverse drug reaction.

What is Unexpected Adverse Reaction?

An adverse reaction, the nature, severity or
outcome of which is not consistent with the
applicable product information.

What is Advanced therapy medicinal

product (ATMP)?
A medicinal product for human use that is
either a gene therapy medicinal product, a
somatic cell therapy product or a tissue
engineered products as defined in Regulation
(EC) No 1394/2007.
What is Clinical trial?
Any investigation in human subjects intended
to discover or verify the clinical,
pharmacological and/or other
pharmacodynamic effects of one or more
investigational medicinal product(s), and/or to
identify any adverse reactions to one or more
investigational medicinal product(s) and/or to
study absorption, distribution, metabolism
and excretion of one or more investigational
medicinal product(s) with the objective of
ascertaining its (their) safety and/or efficacy.
This includes clinical trials carried out in either
one site or multiple sites, whether in one or
more Member State [Dir 2001/20/EC Art 2(a)].

When do you consider an event to be

serious?
An adverse event is considered serious if it
meets one or more of the following criteria.
results in death, or is life-threatening;
requires inpatient hospitalization or
prolongation of existing hospitalization
 results in persistent or significant disability
or incapacity;
results in a congenital anomaly (birth
defect); or
is otherwise "medically significant" (i.e.,
that it does not meet preceding criteria,
but is considered serious because
treatment/intervention would be required
to prevent one of the preceding criteria.

What is mean by Registry?

An organised system that uses observational
methods to collect uniform data on specified
outcomes in a population defined by a
particular disease, condition or exposure.

What is Quality system of a

pharmacovigilance system?
The organisational structure, responsibilities,
procedures, processes and resources of the
pharmacovigilance system as well as
appropriate resource management,
compliance management and record
management.
What are case submission timelines to
regulatory authority?
Various manufacturers have set their own
timelines to avoid any late cases.
Timelines changes from one drug to
another and also on basis of seriousness
and causality.
The most common timelines are as
follows:
Death/Life-threatening cases: 7 days
Other seriousness criteria: 15 days
Non-serious: 90 days

What are Unsolicited or Spontaneous

reports?
An unsolicited report or communication is
received from a healthcare professional,
patient or consumer to a competent
authority, marketing authorisation holder or
other organization that describes one or
more suspected adverse reaction in a patient
who was given one or more medicinal product
and that does not derived from a study or any
organized data collection system.
Examples of Unsolicited or Spontaneous
reports:
Direct reports from patients, consumers,
healthcare professionals etc.
Medical information enquiries
Literature reports
Internet/digital media (website, internet
forum, chat room, blog, social network)

What are Solicited/ Non-spontaneous

reports?
Solicited reports of suspect adverse reactions
are those derived from organized data
systems, which include clinical trials, non-
interventional studies, registries, post-
approval names patient use programs, other
patient support and disease management
programs, surveys of patients or healthcare
providers, or information gathering on efficacy
or patient compliance.
Examples of Solicited/ Non-spontaneous
reports:
Clinical trials
Non-interventional studies
Registries
 Post-approval named patient programs
Patient support programs (PSPs)
Surveys of patients/HCPs

What is Day Zero means?

The first date on which any representative of
an organization was first notified of the
minimum essential elements for expedited
reporting. This date also implies in when any
of the company partner/ vendor receives the
report.

What is SUSAR?
A suspected unexpected serious adverse
reaction is known as a SUSAR.
A SUSAR is defined as an untoward and
unintended response to a study drug, which is
not listed in the applicable product
information, and meets one of the following
serious criteria: results in death, is life-
threatening, requires hospitalisation or
prolongation of an existing hospitalisation,
results in persistent or significant disability or
incapacity, or is a congenital anomaly or birth
defect.
What are reporting timelines for SUSAR
cases?
A SUSAR that meets the seriousness criteria
of life threatening and/or results in death
must be reported within seven (7) calendar
days. A SUSAR which if not life threatening or
does not result in death must be submitted to
the regulatory authorities within fifteen (15)
calendar days.

Name the regulatory bodies in USA, UK,

Japan, Australia and India?
USA: United States Food and drug
administration (USFDA)
UK: Medicines and Healthcare Regulatory
Agency (MHRA)
Japan: Ministry of Health, Labour and Welfare
(MHLW)
Australia: Therapeutic Goods Administration
(TGA)
India: Central Drugs Standard Control
Organization (CDSCO)
What is Volume 9A?
Volume 9A brings together general guidance
on the requirements, procedures, roles and
activities in the field of pharmacovigilance, for
both Marketing Authorisation Holders (MAH)
and Competent Authorities of medicinal
products for human use; it incorporates
international agreements reached within the
framework of the International Conference on
Harmonisation (ICH).

What is GVP (Good pharmacovigilance

practices)?
Good pharmacovigilance practices (GVP) are a
set of measures drawn up to facilitate the
performance of pharmacovigilance in the
European Union (EU). GVP apply to marketing-
authorisation holders, the European
Medicines Agency (EMA) and medicines
regulatory authorities in EU Member States.
They cover medicines authorised centrally via
the Agency as well as medicines authorised at
national level.
What is relation between Volume 9A and
GVP?
With the application of the new
pharmacovigilance legislation from July 2012,
Volume 9A is replaced by the good
pharmacovigilance practice (GVP) guidelines
released by the European Medicines Agency.

When do you consider a case to be

medically confirmed?
A case is considered to be medically
confirmed if it contains at least one event
confirmed or reported by an HCP (Health
Care Professional). HCP can be a physician,
nurse, pharmacist etc.

What do you mean by causality?

Causality is the relationship between a set of
factors. In Pharmacovigilance, causality is the
relationship between the suspect product and
the adverse drug event.
What should a narrative consist of?
A narrative should consist of precise and
concise information about the source of
report, patient demographics, patient’s
medical history, concomitant medications,
suspect product details and adverse event
details in an orderly manner.

What is WHO DD?

The WHO Drug Dictionary (WHO DD) is an
international classification of drugs providing
proprietary and non-proprietary names of
medicinal products used in different
countries, together with all active ingredients.
It is managed by UMC (Uppsala
Monitoring Centre).
It is used by pharmaceutical companies,
clinical trial organizations and drug
regulatory authorities for identifying drug
names in spontaneous ADR reporting
(and pharmacovigilance) and in clinical
trials.
What is Dechallenge?
Dechallenge is the clinical decision to
withdraw or discontinue a drug to monitor the
effect on an adverse event.
Dechallenge means that a drug that is
suspected of causing the event is
withdrawn.
A dechallenge is positive when after
removal of the drug the adverse event
subsides or disappears.
A dechallenge is negative when the event
persists even after removal of the drug i.e.
a causal relationship is unlikely.

What is Rechallenge?
Rechallenge is the point at which a drug is
given again to a patient after its previous
withdrawal.
In the instance you have a positive
dechallenge (AE subsides or disappears after
you remove the drug), reintroducing the drug
represents a rechallenge.
A positive rechallenge (i.e., the AE
reappears when treatment is restarted),
strongly suggests a causal relationship.
What are different frequencies of ADRs?
In giving an estimate of the frequency of ADRs
the following standard categories are
recommended:
Very common > 10%
Common (frequent) >1% and <10%
Uncommon (infrequent) >0.1% and <1%
Rare >0.01% and <0.1%
Very rare <0.01%

Do you have any idea about VigiBase?

It is the largest repository of drug safety data
across the globe. It is maintained and
managed by Uppsala Monitoring Centre
(UMC).

What is CIOMS?
The Council for International Organizations of
Medical Sciences (CIOMS) is an international,
non-governmental, non-profit organization
established jointly by WHO and UNESCO in
1949.
CIOMS represents a substantial proportion of
the biomedical scientific community through
its member organizations, which include many
of the biomedical disciplines, national
academies of sciences and medical research
councils. CIOMS mission is to advance public
health through guidance on health research
and policy including ethics, medical product
development and safety. CIOMS is in official
relations with WHO and is an associate
partner of UNESCO.
CIOMS I: The international reporting form
CIOMS II: Periodic safety update reports
manual
CIOMS III: Core data sheets
CIOMS IV: Benefit-risk assessments
CIOMS V: Practical issues in
Pharmacovigilance
CIOMS VI: Clinical trial safety data
CIOMS VII: Development safety update
reports
CIOMS VIII: Practical Aspects of Signal
Detection in Pharmacovigilance
What are different GVP modules?
Module I – Pharmacovigilance systems and
their quality systems
Module II – Pharmacovigilance system master
file
Module III – Pharmacovigilance inspections
Module IV – Pharmacovigilance audits
Module V – Risk management systems (Rev.2)
Module VI – Collection, management and
submission of reports of suspected adverse
reactions to medicinal products (Rev. 2)
Module VI Addendum I – Duplicate
management of suspected adverse reactions
reports
Module VII – Periodic safety update report
Module VIII – Post-authorisation safety studies
Module VIII Addendum I – Requirements and
recommendations for the submission of
information on non-interventional post-
authorisation safety studies (Rev.3)
Module IX – Signal management
Module IX Addendum I – Methodological
aspects of signal detection from spontaneous
reports of suspected adverse reactions
Module X – Additional monitoring
Module XV – Safety communications (Rev.1)
Module XVI – Risk minimisation measures:
selection of tools and effectiveness indicators
(Rev. 2)
Module XVI Addendum I – Educational
materials
Module XVI Addendum II – Methods for
effectiveness evaluation

What is mean by Compassionate use of a

medicinal product?
Making a medicinal product available for
compassionate reasons to a group of patients
with a chronically or seriously debilitating
disease or whose disease is considered to be
life-threatening, and who cannot be treated
satisfactorily by an authorised medicinal
product (the medicinal product concerned
must either be subject of an application for a
central marketing authorisation or must be
undergoing clinical trials).
What is Individual case safety report
(ICSR) or Adverse (drug) reaction report?
Format and content for the reporting of one or
several suspected adverse reactions to a
medicinal product that occur in a single patient
at a specific point of time.

What is Medical device?

Any instrument, apparatus, appliance, software,
material or other article, whether used alone or
in combination, including the software
intended by its manufacturer to be used
specifically for diagnostic and/or therapeutic
purposes and necessary for its proper
application, intended by the manufacturer to
be used for human beings for the purpose of:
diagnosis, prevention, monitoring,
treatment or alleviation of disease,
diagnosis, monitoring, treatment, alleviation
of disease;
diagnosis, monitoring, treatment, alleviation
of or compensation for an injury or
handicap;
 investigation, replacement or modification
of the anatomy or of a physiological
process;
control of conception;
and which does not achieve its principal
intended action in or on the human body by
pharmacological, immunological or metabolic
means, but which may be assisted in its
function by such means [Dir 93/42/EEC Art 1(2)
(a)].

What is Non-interventional trial or Non-

interventional study?
A study where the medicinal product(s) is (are)
prescribed in the usual manner in accordance
with the terms of the marketing authorisation.
The assignment of the patient to a particular
therapeutic strategy is not decided in advance
by a trial protocol but falls within current
practice and the prescription of the medicine is
clearly separated from the decision to include
the patient in the study. No additional
diagnostic or monitoring procedures shall be
applied to the patients and epidemiological
methods shall be used for the analysis of
collected data.
What is PASS?
Any study relating to an authorised medicinal
product conducted with the aim of identifying,
characterising or quantifying a safety hazard,
confirming the safety profile of the medicinal
product, or of measuring the effectiveness of
risk management measures.
A post-authorisation safety study may be an
interventional clinical trial or may follow an
observational, non-interventional study design.
Special Situation
Scenarios
What are Special Situation scenarios in
Pharmacovigilance?
The special situations are non-standard
medical conditions that provide valuable
information about medicinal product, even
when they don’t occur in association with an
adverse event or medical condition.
Therefore, it should be reported for:
Complying with regulatory guidelines
Meeting protocol specific requirements
Benefit-risk assessments of medicines
Examples of special situations are:
Overdose
Off-label use
Drug abuse and misuse
Medication errors
Lack of Efficacy (LOE)
Pregnancy
Occupational exposure
Product counterfeit
Disease progression
Drug interactions
Drug Addiction
Suspected transmission of infectious
agents via a medicinal product (STIAMP)
What is Abuse of a medicinal product?
Persistent or sporadic, intentional excessive
use of medicinal products which is
accompanied by harmful physical or
psychological effects.

What is Misuse of a medicinal product?

Situations where the medicinal product is
intentionally and inappropriately used not in
accordance with the authorised product
information.

What is Off-label use?

Situations where a medicinal product is
intentionally used for a medical purpose not
in accordance with the terms of the marketing
authorisation.
Examples include the intentional use of a
product in situations other than the ones
described in the authorised product
information, such as:
Medicine used for disease or medical
condition that it is not approved to treat
Medicine administration through different
route or method of administration
 Medicine used with different dose
(posology)
Medicine used in different group of
patients (population)

What is Medication error?

A medication error is an unintended failure
in the drug treatment process that leads to,
or has the potential to lead to, harm to the
patient. A failure in the drug treatment
process does not refer to lack of efficacy of
the drug, rather to human or process
mediated failures.

Medication errors may occur at all stages of

the drug treatment process (e.g. prescribing,
storage, dispensing, preparation,
administration).

What is difference in off-label use and

Medication Error?
The element of ‘intention’ differentiates some
of the off-label uses from the medication
error at prescriber level.
 For example, if the doctor intentionally
prescribes/administers a drug by
unauthorised route of administration, this
would be called off-label use. However, if
the doctor unintentionally (i.e. by
mistake/error) prescribes/administers a
drug by unauthorised route of
administration, this would be called a
medication error.

What is Overdose?
Administration of a quantity of a medicinal
product given per administration or
cumulatively which is above the maximum
recommended dose according to the
authorised product information.

What is Occupational exposure to a

medicinal product?
For the purpose of reporting cases of
suspected adverse reactions, an exposure to a
medicinal product as a result of one’s
professional or non-professional occupation.
It does not include the exposure to one of the
ingredients during the manufacturing process
before the release as finished product.
What is Lack of Efficacy (LOE)?
The lack of expected or desired effect related
to a therapy.
Lack of efficacy/effect is an evidence of less
than the expected effect of a product

What is Product counterfeit?

Counterfeits of original medicinal products
which look like the original may:
Contain substances of lower quality or the
wrong dose
Be deliberately and fraudulently
mislabelled with the intention to avoid
identifying the source
Have counterfeit packaging, wrong
ingredients or a lower proportion of the
active substance

What is Disease progression?

1.All atypical or accelerated progression* of
disease which indicates rather poor efficacy of
the company product.
* E.g. faster progression than expected, or may
include other unexpected elements of
progression that may be attributed to
treatment by the suspected product and / or
2. The doctor suggests that the progression is
causally related to treatment with a company
product (rather points to the lack of
effectiveness) or the causation was not
commented on (then it has to be obtained
within the supplementary information).

What is Drug interactions?

Drug interaction is a reaction between two (or
more) drugs or between a drug and a food,
beverage, or supplement. Taking a drug while
having certain medical conditions can also
cause a drug interaction.
For example, taking a nasal decongestant if you
have high blood pressure may cause an
unwanted reaction

What is Drug Addiction?

It is a disease that negatively affects a person’s
brain and behavior.
A person can become obsessed with any
legal or illegal drugs. Some people can get
addicted to certain medications.
This addiction gradually starts developing
when the individual continues to consume
the drug despite the impairment it causes.
 Nicotine, marijuana and alcohol are
commonly misused drugs in today’s
world.

What is Suspected transmission of

infectious agents via a medicinal
product (STIAMP)?
Any organism, virus or infectious particle
(e.g. prion proteins of spongiform
encephalopathy), pathogenic and
nonpathogenic, is considered to be an
infectious agent. Transmission of infectious
agents can be derived from clinical
symptoms and laboratory findings.
Medical Dictionary
for Regulatory
Activities
(MedDRA)
What is MedDRA? Explain the hierarchy in
MedDRA?
MedDRA (Medical Dictionary for Regulatory
Activities) is a clinically-validated international
medical terminology used by regulatory
authorities and the regulated biopharmaceutical
industry.
MedDRA hierarchy:
System Organ Class (SOC)
High Level Group Term (HLGT)
High Level Term (HLT)
Preferred Term (PT)
Lower Level Term (LLT)

How many times MedDRA is updated in a

year?
The MSSO release updated MedDRA versions
twice a year - in March and September.
The English translation is released on the 1st of
March and September and all other translations
are released on the 15th.

What is the latest version of MedDRA?

The current MedDRA version is 24.1
How many SOCs are there in MedDRA?
Currently there are 27 SOCs in MedDRA.

What are SMQs?

Standardised MedDRA Queries (SMQs) are
tools developed to facilitate retrieval of
MedDRA-coded data as a first step in
investigating drug safety issues in
pharmacovigilance and clinical development.
SMQs are validated, pre-determined sets of
MedDRA terms grouped together after
extensive review, testing, analysis, and expert
discussion.
SMQs are a unique feature of MedDRA and
provide a strong tool to support safety analysis
and reporting.
The SMQ topics are intended to address the
important pharmacovigilance topics needed
by regulatory and industry users.
The SMQs are maintained with each release of
MedDRA by the MSSO.

Currently, over 100 SMQs have been created.

Additional SMQs are created as the need arises.
The following are a small sampling of SMQs that
are available to users today:
Anaphylactic reaction
Central nervous system vascular disorders
Convulsions
COVID-19
Depression and suicide/self-injury
Drug abuse, dependence and withdrawal
Hyperglycaemia/new onset diabetes mellitus
Hypersensitivity
Ischaemic heart disease
Lack of efficacy/effect
Medication errors
Severe cutaneous adverse reactions
Aggregate
Reporting
What are aggregate reports?
Aggregate report is the process that reviews the
cumulative safety information from a wide range
of sources, on a periodic basis and submits the
findings to regulators worldwide. The aggregate
report examines and summarizes all existing
safety experience with a medicinal product.
Cumulative or Aggregate reporting, also
known as Periodic Reporting, plays a key role
in the safety assessment of drugs. Aggregate
reporting involves the compilation of safety
data for a drug over a prolonged period of
time (months or years), as opposed to single-
case reporting which, by definition, involves
only individual AE reports.
The periodic reports play an important role in
risk-benefit evaluation of the drug and involves
collective analysis of cases in the database,
monitoring regulatory actions, literature
searches etc. They are required to be
submitted to various regulatory agencies to
comply with the regulatory requirements. The
advantage of aggregate reporting is that it
provides a broader view of the safety profile of
a drug.
What is DIBD?
Developmental International Birth Date (DIBD)
is the date of approval of the first authorization
for conducting an interventional clinical trial in
any country.
The first data lock point for the DSUR is the first
anniversary of the DIBD.

What is IBD?
International Birth Date (IBD) is the date of the
first marketing authorisation for any product
containing the active substance granted to any
company in any country in the world.

If a marketing authorisation holder has no

information on the actual IBD for a product, it
should first refer to listings of birth dates that
some regions develop and make publicly
available. If the product is not included in any
listing, it should propose to the regulatory
authority a birth date that is based on the
earliest known marketing authorisation of the
substance and then obtain the regulatory
authority’s agreement.
What is DLP?
The Data Lock Point (DLP) represents the cut-
off date for data and analyses presented in a
document.
For a periodic safety update report (PSUR),
the date designated as the cut-off date for
data to be included in a PSUR.
For a periodic benefit-risk evaluation report
(PBRER), the date designated as the cut-off
date for data to be included in a PBRER,
based on the international birth date (see
GVP Annex IV, ICH-E2C(R2) Guideline).
For a development safety update report
(DSUR), the date designated as the cut-off
date for data to be included in a DSUR,
based on the development international
birth date (see ICH-E2F Guideline, Volume
10 of the Rules Governing Medicinal
Products in the EU).

What is DSUR?
Format and content for periodic reporting on
drugs under development.
 Development Safety Update Report (DSUR)
is Comprehensive, thoughtful annual review
and evaluation of pertinent safety
information collected during the reporting
period related to a drug under
investigation, whether or not it is marketed.
A DSUR provides information to assure
regulators that sponsors are adequately
monitoring and evaluating the evolving
safety profile of the investigational drug.

What is Periodic Safety Update Report

(PSUR) / Periodic Benefit-Risk Evaluation
Report (PBRER)?
Pharmacovigilance document intended to
provide an evaluation of the risk-benefit
balance of a medicinal product for submission
by marketing authorisation holders at defined
time points during the post-authorisation
phase.
A PSUR / PBRER also evaluates the
effectiveness of the risk minimisation measures
described in the RMP.
A PSUR / PBRER provides an analysis of the risk-
benefit profile of a medicinal product based on
the safety, efficacy and effectiveness
information that becomes available in the
reporting period and in the context of the
cumulative experience with the medicinal
product since DIBD.

What is the difference between PBRER and

PSUR?
A PSUR primarily served as an interval safety
report whereas a PBRER is meant to be a
cumulative benefit-risk report.

Unlike a PSUR, a PBRER includes data on

efficacy and effectiveness from ongoing or
updated clinical trials and cohort studies.

What are different sections of PBRER?

Title page
Executive Summary
Table of Contents
1. Introduction
2. Worldwide Marketing Approval Status
3. Actions Taken in the Reporting Interval for
Safety Reasons
4. Changes to Reference Safety Information
5. Estimated Exposure and Use Patterns
5.1 Cumulative Subject Exposure in Clinical
Trials
5.2 Cumulative and Interval Patient
Exposure from Marketing Experience
6. Data in Summary Tabulations
6.1 Reference Information
6.2 Cumulative Summary Tabulations of
Serious Adverse Events from Clinical Trials
6.3 Cumulative and Interval Summary
Tabulations from Post-marketing Data
Sources
7. Summaries of Significant Findings from
Clinical Trials during the Reporting Period
7.1 Completed Clinical Trials
7.2 Ongoing Clinical Trials
7.3 Long-term Follow-up
7.4 Other Therapeutic Use of Medicinal
Product
7.5 New Safety Data Related to Fixed
Combination Therapies
8. Findings from Non-interventional Studies
9. Information from Other Clinical Trials and
Sources
10. Non-clinical Data
11. Literature
12. Other Periodic Reports
13. Lack of Efficacy in Controlled Clinical Trials
14. Late-Breaking Information
15. Overview of Signals: New, Ongoing, or
Closed
16. Signal and Risk Evaluation
16.1 Summary of Safety Concerns
16.2 Signal Evaluation
16.3 Evaluation of Risks and New
Information
16.4 Characterisation of Risks
16.5 Effectiveness of Risk Minimisation (if
applicable)
17. Benefit Evaluation
17.1 Important Baseline
Efficacy/Effectiveness Information
17.2 Newly Identified information on
Efficacy/Effectiveness
17.3 Characterisation of Benefits
18. Integrated Benefit-risk Analysis for Approved
Indications
18.1 Benefit-risk Context - Medical Need and
Important Alternatives
18.2 Benefit-risk Analysis Evaluation
19. Conclusions and Actions
20. Appendices

What is ACO?
The addendum to the clinical overview (ACO)
collects all cumulated effectiveness and safety
data related to a medicinal product since MA or
its last renewal, in order to obtain a new renewal
for any medicinal product. It is an essential safety
report to reevaluate the current benefit/risk
balance, assuring patients’ health and safety.
A critical discussion should be provided
within the Addendum to the Clinical
Overview.
It should address the current benefit-risk
balance for the product on the basis of the
PSUR data and safety/efficacy data
accumulated since the granting of the MA or
the last renewal, making reference to
relevant new information in the public
domain.
What information should ACO contains?
The Addendum to the Clinical Overview should
contain the following information:

History of pharmacovigilance system

inspections and an analysis of the impact of
the findings overall on the benefit-risk
balance of the medicinal product.
Worldwide marketing authorisation status
Actions taken for safety reasons during the
period covered since the initial marketing
authorisation or since the last renewal until
to the DLP of the renewal
Significant changes made to the Reference
Information (RI) during the period covered
since the initial marketing authorisation or
since the last renewal
Estimated exposure and used patterns
Data in summary tabulations
Summaries of significant safety and efficacy
findings from clinical trials and
noninterventional studies during the period
covered by the renewal
Overview of signals
Signal and risk evaluation
 Relevant information on patterns of
medication errors and potential medication
errors during the period covered by the
renewal
Literature
Benefit evaluation
Benefit-risk balance
Late-breaking information

What is DHPC?
A communication intervention by which
important information is delivered directly to
individual healthcare professionals by a
marketing authorisation holder or by a
competent authority, to inform them of the need
to take certain actions or adapt their practices in
relation to a medicinal product.

What is EU reference date or Union

reference date?
For medicinal products containing the same
active substance or the same combination of
active substances, the date of the first marketing
authorisation in the EU of a medicinal product
containing that active substance or that
combination of active substances
or if this date cannot be ascertained, the earliest
of the known dates of the marketing
authorisations for a medicinal product containing
that active substance or that combination of
active substances.

What is PADER?
A PADER (Periodic Adverse Drug Experience
Report) is a part of post-cumulative safety
reports which need to be submitted to the
United States Food and Drug Administration
(USFDA).

What is frequency of PADER submission?

PADERs are required to be submitted quarterly
for the first 3 years after drug approval in the
USA, and annually thereafter.

What information should a PADER contains?

A PADER should contains:
A narrative summary and analysis of all 15
day alert reports
A MedWatch form (3500A) for each ADR,
which did not report as 15 day expedited
report.
Actions taken in reporting interval period
 Periodic reporting, except for
information on 15-day alert reports
Folllow up information to adverse drug
experiences submitted in a periodic
report may be submitted in the next
periodic report.

What is REMS?
A Risk Evaluation and Mitigation Strategy
(REMS) is a drug safety program that the
U.S. Food and Drug Administration (FDA)
can require for certain medications with
serious safety concerns to help ensure the
benefits of the medication outweigh its
risks.
REMS are designed to reinforce
medication use behaviors and actions
that support the safe use of that
medication.
While all medications have labeling
that informs health care stakeholders
about medication risks, only a few
medications require a REMS
REMS are not designed to mitigate all the
adverse events of a medication, these are
communicated to health care providers in
the medication’s prescribing information.
Rather, REMS focus on preventing,
monitoring and/or managing a specific
serious risk by informing, educating and/or
reinforcing actions to reduce the frequency
and/or severity of the event.
Signal Management
What is Signal?
Information arising 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
events, either adverse or beneficial, that is judged
to be of sufficient likelihood to justify verificatory
action.
New aspects of a known association may
include changes in the frequency, distribution
(e.g. gender, age and country), duration,
severity or outcome of the adverse reaction.
For the purpose of monitoring data in the
EudraVigilance database, only signals related
to an adverse reaction shall be considered.
For the purpose of Section 16.2 of the
periodic benefit-risk evaluation report, signals
relate to adverse effects.
1. Signals are continuously monitored and
evaluated by the company.
2. New signals which emerge, remain ongoing,
or are closed during the reporting period are
presented in the PSUR / PBRER.
What is Closed signal?
In periodic benefit-risk evaluation reports, a signal
for which an evaluation was completed during the
reporting interval.
A safety signal can be closed either because it is
refuted or because it is determined to be a
potential or identified risk following evaluation.

What is Ongoing signal?

In periodic benefit-risk evaluation reports, a signal
that remains under evaluation at the data lock
point

What is Newly identified signal?

In periodic benefit-risk evaluation reports, a signal
first identified during the reporting interval,
prompting further actions or evaluation.

What is Confirmed signal?

For the signal management process in the EU, a
validated signal entered in the European
Pharmacovigilance Issues Tracking Tool (EPITT)
that requires further analysis and prioritisation by
the Pharmacovigilance Risk Assessment
Committee (PRAC), according to the PRAC
Rapporteur or (lead) Member State.
What is Non-confirmed signal?
For the signal management process in the EU, a
validated signal entered in the European
Pharmacovigilance Issues Tracking Tool (EPITT) that
does not require further analysis and prioritisation
by the Pharmacovigilance Risk Assessment
Committee (PRAC) at that point in time, according to
the PRAC Rapporteur or (lead) Member State.

What is 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.

What is 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.
What is Refuted signal?
A validated signal which, following further
assessment has been determined to be “false”, i.e. a
causal association cannot be established at that
point in time.
It is noted that for the purpose of the periodic
benefit-risk evaluation report (PBRER) ICH describes
refuted signals as signals that, following evaluation,
have been refuted as “false” signals based on
medical judgment and a scientific evaluation of the
currently available information.

What is 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.
Examples:
major safety issues identified in the context of
ongoing or newly completed studies, e.g. an
unexpectedly increased rate of fatal or life-
threatening adverse events;
 major safety issues identified through the
spontaneous reporting system or publications
in the scientific literature, which may lead to
considering a contraindication, a restriction of
use of a medicinal product or its withdrawal
from the market;
major safety-related regulatory actions outside
the EU, e.g. a restriction of use of a medicinal
product or its suspension.

What is Signal assessment?

The process of further evaluating a validated signal
taking into account all available evidence, to
determine whether there are new risks causally
associated with the active substance or medicinal
product or whether known risks have changed.
This process may include non-clinical and
clinical data and should be as comprehensive as
possible regarding the sources of information.
Within the signal management process in the
EU, signal assessment by the Pharmacovigilance
Risk Assessment Committee (PRAC), is, following
PRAC’s initial signal analysis and prioritisation,
the process of evaluating all available data
relevant to a signal to determine the need for
any regulatory action.
What is Signal management process?
A set of activities performed to determine
whether, based on an examination of individual
case safety reports, 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.

The signal management process shall include the

following activities: signal detection, signal
validation, signal confirmation, signal analysis and
prioritisation, signal assessment and
recommendation for action.

What is Signal detection?

The process of looking for and/or identifying
signals using data from any source (based on
CIOMS VIII15).

What is Signal prioritisation?

The process, continuously performed throughout
signal management, which aims to identify those
signals suggesting risks with a potential important
patients’ or public health impact or which may
significantly affect the risk-benefit balance of the
medicinal product and thus require urgent
attention and management without delay (based
on SCOPE Best Practice Guide on Signal
Management16).

What is Signal validation?

Process of evaluating the data supporting the
detected signal in order to verify 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.
This evaluation should take into account the
strength of the evidence, the clinical relevance
and the previous awareness of the association.
Risk Management
What is Identified risk?
Definition according to GVP Annex I (Rev 3):
An untoward occurrence for which there is
adequate evidence of an association with the
medicinal product of interest.
Explanatory wording provided in GVP module V
(Rev 2):
Undesirable clinical outcomes for which there is
sufficient scientific evidence that they are caused
by the medicinal product.
Identified risks can arise e.g. from signal
evaluation and are described and classified (i.e.,
important or not important) in the PSUR / PBRER.
Identified risks have usually been observed in
clinical trials or in clinical practice and are
described in the SmPC. The causal relationship is
already documented.
Examples:
an adverse reaction adequately
demonstrated in non-clinical studies and
confirmed by clinical data;
an adverse reaction observed in well-
designed clinical trials or epidemiological
studies for which the magnitude of the
difference, compared with the comparator
group on a parameter of interest suggests a
causal relationship;
 an adverse reaction suggested by a number
of well-documented spontaneous reports
where causality is strongly supported by
temporal relationship and biological
plausibility, such as anaphylactic reactions or
application site reactions (see ICH-E2F
Guideline, Volume 10 of the Rules Governing
Medicinal Products in the EU).

In a clinical trial, the comparator may be placebo,

an active substance or non-exposure.

Adverse reactions included in section 4.8 of the

summary of product characteristics (SmPC) are
also considered identified risks, unless they are
class-related reactions which are mentioned in
the SmPC but which are not specifically described
as occurring with this product (these would
normally be considered as a potential risk)).

What is Potential risk?

Definition according to GVP Annex I (Rev 3):
An untoward occurrence for which there is some
basis for suspicion of an association with the
medicinal product of interest but where this
association has not been confirmed.
Explanatory wording provided in GVP module V
(Rev 2):
Undesirable clinical outcomes for which there is
scientific evidence to suspect the possibility of a
causal relationship with the medicinal product,
but where there is currently insufficient evidence
to conclude that this association is causal.
Potential risks have not necessarily been
observed in clinical trials or in the clinical practice;
however, preclinical or clinical considerations
point to a possible causal association to the
medicinal product.
Potential risks can be identified e.g. from signal
evaluation and are described and classified (i.e.,
important or not important) in the PSUR / PBRER.
Examples:
non-clinical toxicological findings that have
not been observed or resolved in clinical
studies;
adverse events observed in clinical trials or
epidemiological studies for which the
magnitude of the difference, compared with
the comparator group (placebo or active
substance, or unexposed group), on the
parameter of interest raises a suspicion of,
but is not large enough to suggest, a causal
relationship;
 a signal arising from a spontaneous adverse
reaction reporting system;
an event known to be associated with other
active substances within the same class or
which could be expected to occur based on
the properties of the medicinal product
(based on ICH-E2F Guideline, Volume 10 of
the Rules Governing Medicinal Products in
the EU).

What is Important risk?

Definition according to GVP Annex I (Rev 3):
An identified risk or potential risk that could have
an impact on the risk-benefit balance of the
product or have implications for public health.
Explanatory wording provided in GVP module V
(Rev 2):
The RMP should focus on the important identified
risks that are likely to have an impact on the risk-
benefit balance of the product. An important
identified risk to be included in the RMP would
usually warrant:
Further evaluation as part of the
pharmacovigilance plan (e.g. to investigate
frequency, severity, seriousness and outcome
of this risk under normal conditions of use,
which populations are particularly at risk);
 Risk minimisation activities: product
information advising on specific clinical
actions to be taken to minimise the risk, or
additional risk minimisation activities.

The important potential risks to be included in

the RMP are those important potential risks that,
when further characterised and if confirmed,
would have an impact on the risk-benefit balance
of the medicinal product.
Important risks are identified, characterised,
and monitored in the DSUR; the RMP, and in
the PSUR / PBRER.
To define the important risks of a medicinal
product, the overall knowledge on the safety
profile of a drug is evaluated (e.g.,
mechanisms of action, epidemiology of the
populations exposed, risk factors or risk
groups, preclinical, clinical and, if available,
post-marketing experience).

What is Important identified risk and

Important potential risk?
An identified risk or potential risk that could have
an impact on the risk-benefit balance of the
product or have implications for public health.
What constitutes an important risk will depend
upon several factors, including:
the impact on the individual
the seriousness of the risk
the impact on public health.

Normally, any risk that is likely to be included in

the contraindications or warnings and
precautions section of the product information
should be considered important.

What is missing information?

Definition according to GVP Annex I (Rev 3):
(Critical) gaps in knowledge about a medicinal
product, related to safety or use in particular
patient populations, which could be clinically
significant.
Explanatory wording provided in GVP module V
(Rev 2):
Gaps in knowledge about the safety of a
medicinal product for certain anticipated
utilisation (e.g. long-term use) or for use in
particular patient populations, for which there is
insufficient knowledge to determine whether the
safety profile differs from that characterised so
far.
 Missing information is identified,
characterised, and monitored in the RMP and
the PSUR / PBRER.
Typical examples of missing information are
the use of a medicinal product in pregnant
and lactating women or in the paediatric
population, if there are not adequate clinical
studies in these patients. The decision on
whether the lack of safety information in a
specific population is critical (=missing
information) is based on clinical
considerations.

What is Risk-benefit balance?

An evaluation of the positive therapeutic effects
of the medicinal product in relation to the risks,
i.e. any risk relating to the quality, safety or
efficacy of the medicinal product as regards
patients’ health or public health.

The risk-benefit balance of a medicinal product is

continuously monitored through
pharmacovigilance activities and periodical safety
reports, such as DSURs and PBRERs.
What is Safety concern?
An important identified risk, important potential
risk or missing information.
The safety concerns of a medicinal product are
identified, characterised, and monitored in the
DSUR; the RMP, and in the PSUR / PBRER.
The ICH-E2E Guideline (see GVP Annex IV) uses
the terms safety issue and safety concern
interchangeably with the same definition for
safety concern as defined in the ICH-E2C(R2)
Guideline.

What is RMP?
Risk Management Plan (RMP) is a dynamic, stand-
alone document that should be updated
throughout the life-cycle of the medicinal product
to reflect the increasing knowledge on risks and
benefits and the post-marketing experience with
the product.
A detailed description of the risk management
system.
The risk management plan established by the
marketing authorisation holder shall contain the
following elements:
an identification or Characterisation of the
safety profile of the medicinal product(s)
concerned;
 an indication of how to characterise further
the safety profile of the medicinal product(s)
concerned; (c) a documentation of measures
to prevent or minimise the risks associated
with the medicinal product, including an
assessment of the effectiveness of those
interventions;
a documentation of post-authorisation
obligations that have been imposed as a
condition of the marketing authorisation

What is RMS?
Risk management system (RMS) is a set of
pharmacovigilance activities and interventions
designed to identify, characterise, prevent or
minimise risks relating to medicinal products,
including the assessment of the effectiveness of
those activities and interventions.
The RMS covers the entire life-cycle of a medicinal
product.

What is Risk minimisation measure or Risk

minimisation activity?
Interventions intended to prevent or reduce the
occurrence of adverse reactions associated with
the exposure to a medicine, or to reduce their
severity or impact on the patient should adverse
reactions occur.

These activities may consist of routine risk

minimisation measures (the summary of product
characteristics, the package leaflet, the labelling,
the pack size, the legal status of the product, and
its formulation) or additional risk minimisation
measures (educational programmes, controlled
access programmes, other additional risk
minimisation measures).
EudraVigilance
What is the EudraVigilance database?
EudraVigilance is the system for managing and
analysing information on suspected adverse
reactions to medicines which have been
authorised or being studied in clinical trials in
the European Economic Area (EEA).

The European Medicines Agency (EMA)

operates the system on behalf of the
European Union (EU) medicines regulatory
network.

What is eRMR?
The eRMR is a tool to perform signal detection
in EudraVigilance. 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.

Users will be able to retrieve different eRMRs

depending on the selected reference period.
These reports will retrieve valid cases
transmitted to the EVPM module only.
What are EVDAS line listing reports?
The EVDAS line listing report provides the user
with the listing of individual cases for a specific
substance/s and specific MedDRA terms when
appropriate. The report also provides the
possibility to restrict the data to a specific
period.

What is EVDAS active substance grouping

report?
The ‘Active substance grouping’ EVDAS report
provides the user with an overview of the
active substances and medicinal products in
the xEVMPD that are grouped under a specific
‘Active Substance high Level’. The report
provides also the possibility to visualise the
corresponding MAHs and serves MAHs in the
identification of active substances of medicinal
products for which they hold a marketing
authorisation in the EEA.
Labelling
What is Labelling?
Information on the immediate or outer
packaging.

What is Reference safety information

(RSI)?
In periodic benefit-risk evaluation reports for
medicinal products, all relevant safety
information contained in the reference
product information (e.g. the company core
data sheet) prepared by the marketing
authorisation holder and which the marketing
authorisation holder requires to be listed in all
countries where it markets the product, except
when the local regulatory authority specifically
requires a modification.

It is a subset of information contained within

the marketing authorisation holder’s reference
product information for the periodic benefit-
risk evaluation report. Where the reference
product information is the company core data
sheet, the reference safety information is the
company core safety information.
What are the core labeling documents?
The core labeling documents include:
CCDS
SmPC
IB
USPI

What is Company Core Data Sheet (CCDS)?

Company Core Data Sheet (CCDS) is a document
that reflects the full company’s knowledge and
data evaluation for a medicinal product.
For medicinal products, a document prepared by
the marketing authorisation holder containing, in
addition to safety information, material related to
indications, dosing, pharmacology and other
information concerning the product.

What is CCSI?
Company Core Safety Information (CCSI) is the
safety information contained in the CCDS.
The CCSI is generally used in all countries where
the company markets the medicinal product and
is the reference information used to determine
listed and unlisted events for the purpose of
periodic reporting for marketed products.
What is SmPC?
Summary of Product Characteristics (SmPC) is a
legal document approved as part of the
marketing authorisation of a medicinal product in
the European Union.
The SmPC is the basis of information for the
healthcare professional on how to use the
medicine. Its information is updated
throughout the life-cycle of the product as
new data emerge.
The SmPC is the reference information used
to determine expected or unexpected status
of events for marketed products for the
purpose of expedited reporting.

Part of the marketing authorisation of a

medicinal product setting out the agreed position
of the product as distilled during the course of
the assessment process which includes the
information described in Article 11 of Directive
2001/83/EC. It is the basis of information for
healthcare professionals on how to use the
product safely and effectively. The package leaflet
is drawn in accordance with the summary of
product characteristics.
What is IB?
Investigator´s Brochure (IB) is a compilation of
the clinical and nonclinical data on the
investigational product(s) that are relevant to the
study of the product(s) in human subjects.
The IB provides the investigators and others
involved in the trial with the information to
facilitate their understanding of the rationale
for, and their compliance with, many key
features of the protocol, such as the dose,
dose frequency/interval, methods of
administration, and safety monitoring
procedures.
The IB also provides insight to support the
clinical management of the study subjects
during the course of the clinical trial.
For investigational products not yet
authorised, the IB serves as the CCDS.

What is USPI?
United States Prescribing Information (USPI) sets
out the agreed usage of the drug. It provides
information on usage for healthcare
professionals and is an intrinsic part of the
application for marketing authorisation of a new
drug or medicine within the United States.
What is Package leaflet?
A leaflet containing information for the user
which accompanies the medicinal product.
Pharmacovigilance
System Master File
(PSMF)
What is Pharmacovigilance system master
file (PSMF)?
A detailed description of the pharmacovigilance
system used by the marketing authorisation
holder with respect to one or more authorised
medicinal products.
The PSMF shall be located either at the site in
the EU where the main pharmacovigilance
activities of the marketing authorisation
holder are performed or at the site in the EU
where the qualified person responsible for
pharmacovigilance operates.
It is a requirement of the marketing
authorisation application that summary
information about the pharmacovigilance
system is submitted to the competent
authorities. This summary includes
information on the location of the PSMF.

What are objectives of PSMF?

The PSMF shall describe the pharmacovigilance
system and support/document its compliance
with the requirements.
It shall contribute to the appropriate planning
and conduct of audits by the applicant or
marketing authorisations holder(s), the fulfilment
of supervisory responsibilities of the QPPV, and of
inspections or other verification of compliance by
national competent authorities.
The PSMF provides an overview of the
pharmacovigilance system, which may be
requested and assessed by national competent
authorities during marketing authorisation
application(s) or post-authorisation.
Through the production and maintenance of the
PSMF, the marketing authorisation holder and
the QPPV should be able to:
gain assurance that a pharmacovigilance
system has been implemented in accordance
with the requirements;
confirm aspects of compliance in relation to
the system;
obtain information about deficiencies in the
system, or non-compliance with the
requirements;
obtain information about risks or actual
failure in the conduct of specific aspects of
pharmacovigilance.
What PSMF Content should be?
The content of the file is defined in GVP Module
II. There is no standard template, however, the
following sections of the PSMF main body are
provided as a generalized guideline to indicate
the broad nature of the required content:
Details of the qualified person responsible
for pharmacovigilance (QPPV)
Details of the organization structure of the
company that actually holds the Marketing
Authorisation or applies for the Marketing
Authorisation
Details of all of the sources of the relevant
safety data
Details of all electronic (computerized)
systems and databases
Details of all pharmacovigilance processes
Details of the performance of all drug safety
systems
Details of all quality control systems
Annexures
 Vaccine
pharmacovigilance
What is Vaccine pharmacovigilance?
The science and activities relating to the
detection, assessment, understanding and
communication of adverse events following
immunisation and other vaccine- or
immunisation-related issues, and to the
prevention of untoward effects of the vaccine or
immunization.

In this definition, immunisation means the usage

of a vaccine for the purpose of immunising
individuals (see CIOMS-WHO20), which in the EU
is preferably referred to as vaccination (in the
report of CIOMS/WHO Working Group on
Vaccine Pharmacovigilance the terms
immunisation and vaccination are used
interchangeably20). Usage includes all processes
that occur after a vaccine product has left the
manufacturing/packaging site, i.e. handling,
prescribing and administration of the vaccine
(see CIOMS-WHO20).

What is AEFI?
An adverse event following immunisation (AEFI) is
any untoward medical occurrence which follows
immunisation and which does not necessarily
have a causal relationship with the usage of the
vaccine. The adverse event may be any
unfavourable or unintended sign, abnormal
laboratory finding, symptom or disease. While
this AEFI definition is compatible with the
definition of adverse event applied in the EU, the
AEFI definition is not needed to describe
pharmacovigilance for vaccines in the EU.
However, EU guidance on pharmacovigilance for
vaccines makes use of the terminology suggested
by CIOMS-WHO20 regarding possible causes of
adverse events, turning them into suspected
adverse reactions. A coincidental event is an AEFI
that is caused by something other than the
vaccine product, immunisation error or
immunisation anxiety.

Vaccine product-related reaction?

An adverse event following immunisation that is
caused or precipitated by a vaccine due to one or
more of the inherent properties of the vaccine
product (see CIOMS-WHO21).
In this definition immunisation means the usage
(handling, prescribing and administration) of a
vaccine for the purpose of immunising individuals
(see CIOMS-WHO21), which in the EU is preferably
referred to as vaccination (in the report of
CIOMS/WHO Working Group on Vaccine
Pharmacovigilance the terms immunisation and
vaccination are used interchangeably21).

What is Vaccine quality defect-related

reaction?
An adverse event following immunisation that is
caused or precipitated by a vaccine that is due to
one or more quality defects of the vaccine product
including its administration device as provided by
the manufacturer (see CIOMS-WHO22).
In this definition immunisation means the
usage (handling, prescribing and
administration) of a vaccine for the purpose of
immunising individuals (see CIOMS-WHO22),
which in the EU is preferably referred to as
vaccination (in the report of CIOMS/WHO
Working Group on Vaccine Pharmacovigilance
the terms immunisation and vaccination are
used interchangeably22).
For the purpose of this definition, a vaccine
quality defect is defined as any deviation of the
vaccine product as manufactured from its set
quality specifications
PV Agreements
What is a Pharmacovigilance Agreement
(PVA)?
A pharmacovigilance agreement (PVA) is a
written agreement between the marketing
authorisation holder (MAH) and a third party (to
which the MAH has shared or activities regarding
or impacting pharmacovigilance), which outlines
the responsibilities of each party with regards to
pharmacovigilance.
The detailed procedure of PVA in EU is provided
in Good Pharmacovigilance Practices (GVP)
Module 1.

What is the purpose of pharmacovigilance

agreement?
Pharmacovigilance Agreement means an
agreement entered into by the Parties to set
forth the protocols and procedures for reporting
adverse events and complying with reporting
requirements set forth by Regulatory Authorities.

What are different types of PV Agreements?

Co-development arrangements
Co-Marketing and Licensing
Distribution and Wholesaler Agreements
 Manufacturing arrangements
Purchase agreements/tenders/charitable
donations
Service level agreements
Business service providers for marketing
related activities
Service providers for delegated PV activities
or PV supporting functions
Collaboration arrangement with not-for-profit
organisation
Operational aspects

What is Safety Data Exchange Agreements

(SDEA)?
Safety Data Exchange Agreements (SDEA) are
legal written contracts ensuring that all safety
data regarding a licensed product makes its way
quickly and reliably back to the marketing
authorization holder (MAH) so that they may
fulfill their legal obligations to aggregate safety
data and to submit safety reports in a timely
manner.
What Key aspects should be covered in SDEA?
Definition of different terminologies and
language of communication
Mode of communication
Products and territory for agreement
Exchange of medical or product enquiries and
quality complaints
Exchange of cases - timelines and
responsibilities
Exchange of aggregate reports - timelines and
responsibilities
Exchange of validated signals - timelines,
responsibilities, information on
communication to regulatory authority
Information on pharmacovigilance
management system
Reconciliation method and frequency
Safety database
Responsibility during regulatory inspections
and Audit for PV
Data privacy and confidentiality clause
Business continuity plan (BCP)
Termination clause
Revision details - when and how
Contact details such as phone number, email
ID for communication of safety related details
References

1) UMC (Uppsala Monitoring Centre)

https://www.who-umc.org/education-
training/online-learning/

2) EMA (European Medicines Agency)

https://www.ema.europa.eu/en/human-
regulatory/overview/pharmacovigilance-
overview

3) ICH (International Conference of

Hormonisation)
https://www.ich.org/page/efficacy-guidelines

4) CMDh
https://www.hma.eu/310.html

5) PV training materials on EMA website

https://www.ema.europa.eu/en/human-
regulatory/overview/pharmacovigilance/pha
rmacovigilance-training-materials

6) ICH - MedDRA
https://www.ich.org/page/meddra
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ABOUT AUTHOR

Author is a post-graduate in
Pharmacy from renowned
NIPER institute.

He has a decade of industry

experience in
Pharmacovigilance.

He has expertise in ICSR case

processing, Aggregate reporting,
Signal and Risk Management.

www.pvdrugsafety.com