Guideline on good
pharmacovigilance practices (GVP)
Annex I - Definitions (Rev 2)
Draft of first version finalised by the
Agency in collaboration with
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7
February 2012
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Member States
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Definitions agreed by ERMS FG
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24
January 2012
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Draft adopted by Executive Director
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20
February 2012
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Start of public consultation
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21
February 2012
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End of consultation (deadline for comments)
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18
April 2012
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Revised draft of first version finalised by
the Agency in collaboration with
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20
June 2012
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Member States
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Revised draft agreed by ERMS FG
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21
June 2012
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Revised draft adopted by Executive Director
as final
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22
June 2012
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Date for coming into effect
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2
July 2012
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Preparation of draft Revision 1
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26
November 2012
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Draft Revision 1 agreed by ERMS FG
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6
December 2012
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Draft Revision 1 adopted by Executive
Director as final
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12
December 2012
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Date for coming into effect of Revision 1
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13
December 2012
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Draft of definitions for GVP P I finalised
by the Agency in collaboration
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21
February 2013
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with Member States
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Draft agreed by ERMS FG
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8
March 2013
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Draft adopted by Executive Director
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9
April 2013
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Start of public consultation
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12
April 2013
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End of consultation (deadline for comments)
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12
June 2013
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Revised draft Revision 2* finalised by the
Agency in collaboration with
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23
October 2013
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Member States
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Draft Revision 2 agreed by ERMS FG
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11
November 2013
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Draft Revision 2 adopted by Executive
Director as final
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19
December 2013
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See websites for contact details
European
Medicines Agency www.ema.europa.eu
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The
European Medicines Agency is
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Heads
of Medicines Agencies www.hma.eu
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an agency of the European
Union
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©
European Medicines Agency and Heads of Medicines Agencies, 2014.
Reproduction
is authorised provided the source is acknowledged.
8 January 2014
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*Note: Revision 2 includes the
following:
-
Addition of definitions consulted with the public and finalised for
Module XV (Direct healthcare professional communication);
-
Addition of definitions consulted with the public and finalised for
Considerations P.I (Immunisation, Immunisation anxiety-related reaction,
Immunisation error-related reaction, Target population (vaccine), Vaccination,
Vaccination failure, Vaccine failure, Vaccine pharmacovigilance, Vaccine
product-related reaction, Vaccine quality defect-related reaction);
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Addition of definitions from the European Union Regulatory Network
Incident Management Plan for Medicines for Human Use (Crisis, Incident);
- Amendments to the definitions of Missing
information and Safety concern in order to meet EU legal requirements;
- Move of definition of Important missing
information to explanatory note to definition of Missing information;
- Addition of explanatory notes for the
definition of Off-label use in accordance with Module V;
- Addition of an explanatory note on
abbreviations used in the definition for Immunological medicinal product.
Guideline on good
pharmacovigilance practices (GVP) – Annex I (Rev 2)
EMA/876333/2011 Rev 2
Table of contents
Abuse of a
medicinal product.................................................................................... 6
Advanced
therapy medicinal product (ATMP)................................................................ 6
Adverse
event (AE); synonym: Adverse experience...................................................... 6
Adverse
event following immunisation (AEFI)............................................................... 6
reaction,
Adverse effect, Undesirable effect................................................................ 6
Audit.................................................................................................... 6
Audit
finding(s)................................................................................. 6
Audit plan............................................................................................ 7
Audit
programme........................................................................... 7
Audit
recommendation.................................................................... 7
Clinical
trial.......................................................................................... 7
Closed signal....................................................................................... 7
Company core
data sheet (CCDS)............................................................................. 8
Company core
safety information (CCSI).................................................................... 8
Compassionate
use of a medicinal product.................................................................. 8
Completed
clinical trial............................................................................................. 8
Consumer............................................................................................. 8
Crisis................................................................................................... 8
Data lock
point................................................................................... 9
Development
international birth date (DIBD)................................................................ 9
Development
safety update report (DSUR).................................................................. 9
Direct
healthcare professional communication (DHPC)................................................... 9
EU reference
date; synonym: Union reference date...................................................... 9
Failure to
vaccinate................................................................................................. 9
Generic
medicinal product....................................................................................... 10
Good
pharmacovigilance practices (GVP) for the European Union................................... 10
Healthcare
professional.......................................................................................... 10
Herbal
medicinal product........................................................................................ 10
Homeopathic
medicinal product................................................................................ 10
Identified
risk....................................................................................................... 10
Illegal
purposes................................................................................. 11
Immunological
medicinal product.............................................................................. 11
Immunisation................................................................................. 11
Immunisation
anxiety-related reaction...................................................................... 11
Immunisation
error-related reaction......................................................................... 12
Important
identified risk and Important potential risk................................................... 12
Important
potential risk.......................................................................................... 12
International
birth date (IBD).................................................................................. 13
Investigational
drug............................................................................................... 13
Investigational
medicinal product.............................................................................. 13
Labelling.............................................................................................................. 13
Guideline on good pharmacovigilance practices (GVP) –
Annex I (Rev 2)
EMA/876333/2011 Rev 2 Page 3/25
Medicinal product.................................................................................................. 13
Medicinal
product derived from human blood or human plasma..................................... 13
Minimum
criteria for reporting................................................................................. 14
Missing
information............................................................................................... 14
Misuse of a
medicinal product................................................................................. 14
Misuse of a
medicinal product for illegal purposes....................................................... 14
Name of the
medicinal product................................................................................ 14
Newly
identified signal........................................................................................... 14
Non-interventional
trial; synonym: Non-interventional study.......................................... 15
Occupational
exposure to a medicinal product............................................................. 15
Off-label
use........................................................................................ 15
Ongoing
clinical trial............................................................................................... 15
Ongoing
signal............................................................................... 16
Package
leaflet.................................................................... 16
Periodic
safety update report (PSUR)........................................................................ 16
Pharmacovigilance................................................................................ 16
Pharmacovigilance
system...................................................................................... 16
Pharmacovigilance
system master file (PSMF)............................................................ 17
Post-authorisation
safety study (PASS)..................................................................... 17
Potential
risk...........................................
Quality
adherence............................................................................ 17
Quality
assurance....................................................... 17
Quality
control and assurance.................................................................................. 17
Quality improvements.................................................. 18
Quality of a
pharmacovigilance system..................................................................... 18
Quality
objectives................................................................................... 18
Quality
planning.................................................................................. 18
Quality
requirements.................................................................. 18
Quality
system of a pharmacovigilance system........................................................... 18
Reference
safety information.................................................................................. 18
Registry......................................................................................... 19
Risk-benefit
balance.............................................................................................. 19
Risk
management plan (RMP).................................................................................. 19
Risk
management system...................................................................................... 19
Risk
minimisation activity; synonym: Risk minimisation measure.................................... 19
Risks
related to use of a medicinal product................................................................ 19
Safety
concern............................................................................ 19
Serious
adverse reaction........................................................................................ 20
Signal............................................................................................... 20
Signal
management process................................................................................... 20
Signal
validation.................................................................... 20
Solicited
sources of individual case safety reports....................................................... 21
Spontaneous
report, synonym: Spontaneous notification.............................................. 21
Stimulated
reporting........................................................................ 21
Guideline on good pharmacovigilance practices (GVP) –
Annex I (Rev 2)
EMA/876333/2011 Rev 2 Page 4/25
Summary of product characteristics (SmPC).............................................................. 21
Target
population (treatment); synonym: Treatment target population............................ 22
Target
population (vaccine); synonym: Vaccine target population................................... 22
Traditional
herbal medicinal product.......................................................................... 22
Unexpected
adverse reaction.................................................................................. 22
Upper
management........................................................... 22
Vaccination............................................................................. 23
Vaccination
failure................................................................................................. 23
Vaccine
failure............................................................................... 23
Vaccine
pharmacovigilance.............................................................. 24
Vaccine
product-related reaction.............................................................................. 24
Vaccine
quality defect-related reaction...................................................................... 24
Valid
individual case safety report............................................................................ 25
Validated
signal.................................................................................................... 25
Abuse of a medicinal
product
Persistent or sporadic,
intentional excessive use of medicinal products which is accompanied by harmful
physical or psychological effects [DIR 2001/83/EC Art 1(16)].
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 [Reg (EC)
No 1394/2077 Art 1(1)].
Adverse event (AE);
synonym: Adverse experience
Any untoward medical
occurrence in a patient or clinical trial subject administered a medicinal
product and which does not necessarily have a causal relationship with this
treatment [Dir 2001/20/EC Art 2(m)].
An adverse event can
therefore be any unfavourable and unintended sign (e.g. an abnormal laboratory
finding), symptom, or disease temporally associated with the use of a medicinal
product, whether or not considered related to the medicinal product.
Adverse event following
immunisation (AEFI)
See Vaccine pharmacovigilance, Vaccine product-related reaction,
Vaccine quality defect-related reaction, Immunisation error-related reaction,
Immunisation anxiety-related reaction
Adverse reaction; synonyms: Adverse drug reaction (ADR), Suspected
adverse (drug) reaction, Adverse effect, Undesirable effect
A response to a medicinal product which is noxious and unintended [DIR
2001/83/EC Art 1(11)]1.
Response in this
context means that a causal relationship between a medicinal product and an
adverse event is at least a reasonable possibility (see Annex IV, ICH-E2A
Guideline).
Adverse reactions may
arise from use of the product within or outside the terms of the marketing
authorisation or from occupational exposure [DIR 2001/83/EC Art 101(1)].
Conditions of use outside the marketing authorisation include off-label use,
overdose, misuse, abuse and medication errors.
See also Adverse event, Serious adverse reaction, Unexpected adverse
reaction, Off-label use, Overdose, Misuse of a medicinal product, Abuse of a
medicinal product, Occupational exposure to a medicinal product
Audit
A systematic,
disciplined, independent and documented process for obtaining audit evidence
and evaluating it objectively to determine the extent to which the audit
criteria are fulfilled (see ISO 19011 (3.1)2).
Audit finding(s)
Results of the evaluation of the collected audit evidence against
audit criteria (see ISO19011 (3.4)3).
1 In the context of
clinical trials, an adverse reaction is defined as all untoward and unintended
responses to an investigational medicinal product related to any dose
administered [Dir 2001/20/EC Art 2(n)].
2 International
Organization for Standardization (ISO); www.iso.org
Guideline on good pharmacovigilance practices (GVP) –
Annex I (Rev 2)
EMA/876333/2011 Rev 2
Page 6/25
Audit evidence is necessary to support the
auditor’s results of the evaluation, i.e. the auditor’s opinion and report. It
is cumulative in nature and is primarily obtained from audit procedures
performed during the course of the audit.
See also Audit
Audit plan
Description of
activities and arrangement for an individual audit (see ISO19011 (3.12)4). See also Audit
Audit programme
Set of one or more
audits planned for a specific timeframe and directed towards a specific purpose
(see ISO 19011 (3.11)5).
See also Audit
Audit recommendation
Describes the course of
action management might consider to rectify conditions that have gone awry, and
to mitigate weaknesses in systems of management control (see Sawyer LB et al,
20036).
Audit recommendations
should be positive and as specific as possible. They should also identify who
is to act on them (Sawyer LB et al, 20036).
See also Audit
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)].
See also Ongoing
clinical trial, Completed clinical trial, Investigational medicinal product
Closed signal
In periodic
benefit-risk evaluation reports, a signal for which an evaluation was completed
during the reporting interval (see Annex IV, ICH-E2C(R2) Guideline).
This definition is also applicable to periodic safety update reports.
See also Signal
3 International Organization for Standardization
(ISO); www.iso.org
4 International
Organization for Standardization (ISO); www.iso.org
5 International Organization
for Standardization (ISO); www.iso.org
6 Sawyer LB, Dittenhofer
MA. Sawyer’s Internal Auditing. 5th ed. Altamonte Springs, FL: The IIA Research
Foundation; 2003.
Guideline on good pharmacovigilance practices (GVP) –
Annex I (Rev 2)
EMA/876333/2011 Rev 2
Page 7/25
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 (see Annex IV,
ICH-E2C(R2) Guideline).
See also Company core
safety information
Company core safety
information (CCSI)
For medicinal products,
all relevant safety information contained in 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 the company
markets the product, except when the local regulatory authority specifically
requires a modification (see Annex IV, ICH-E2C(R2) Guideline).
It is the
reference information by which listed and unlisted are determined for the
purposes of periodic reporting for marketed products, but not by which expected
and unexpected are determined for expedited reporting (see Annex IV,
ICH-E2C(R2) Guideline).
See also Company core
data sheet
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) [REG (EC) No 726/2004 Art 83(2)].
Completed clinical
trial
Study for which a final
clinical study report is available (see ICH-E2F Guideline, Volume 10 of the
Rules Governing Medicinal Products in the EU).
See also Clinical trial
Consumer
For the purpose of
reporting cases of suspected adverse reactions, a person who is not a
healthcare professional such as a patient, lawyer, friend or
relative/parent/child of a patient (see Annex IV, ICH-E2D Guideline).
Crisis
In the context of the
European Union Regulatory Network Incident Management Plan for Medicines for
Human Use, a crisis is defined as a situation where, after assessment of the
associated risks, urgent and coordinated action within the EU regulatory
network is required to manage and control the situation (see European Union
Regulatory Network Incident Management Plan for Medicines for Human Use7).
See also Incident
Guideline on good pharmacovigilance practices (GVP) –
Annex I (Rev 2)
EMA/876333/2011 Rev 2
Page 8/25
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
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).
Date includes day and
month (see ICH-E2F Guideline, Volume 10 of the Rules Governing Medicinal
Products in the EU).
See also Periodic safety update report, Development safety update
report, International birth date, Development international birth date
Development
international birth date (DIBD)
Date of first approval
(or authorisation) for conducting an interventional clinical trial in any
country (see ICH-E2F Guideline, Volume 10 of the Rules Governing Medicinal
Products in the EU).
Development safety
update report (DSUR)
Format and content for
periodic reporting on drugs under development (see ICH-E2F Guideline, Volume 10
of the Rules Governing Medicinal Products in the EU).
Direct healthcare
professional communication (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.
DHPCs are not replies to enquiries from healthcare professionals.
EU reference date;
synonym: 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 [DIR 2001/83/EC
Art 107c(5)].
Failure to vaccinate
An indicated vaccine was not administered appropriately for any reason
(see CIOMS-WHO8).
For interpreting what is appropriate, consider the explanatory note
for Immunisation error-related reaction.
See also Vaccination
failure
8 Council for
International Organizations of Medical Sciences (CIOMS). Definition and
application of terms of vaccine pharmacovigilance (report of CIOMS/WHO Working
Group on Vaccine Pharmacovigilance). Genève: CIOMS; 2012.
Guideline on good pharmacovigilance practices (GVP) –
Annex I (Rev 2)
EMA/876333/2011 Rev 2
Page 9/25
A medicinal product
which has the same qualitative and quantitative composition in active
substances and the same pharmaceutical form as the reference medicinal product,
and whose bioequivalence with the reference medicinal product has been
demonstrated by appropriate bioavailability studies [REG (EC) No 726/2004 Art
10(2)(b)].
Good pharmacovigilance
practices (GVP) for the European Union
A set of
guidelines for the conduct of pharmacovigilance in the EU, drawn up based on
Article 108a of Directive 2001/83/EC, by the European Medicines Agency in
cooperation with competent authorities in Member States and interested parties,
and applying to marketing authorisation holders in the EU, the Agency and
competent authorities in Member States.
Healthcare professional
For the purposes of
reporting suspected adverse reactions, healthcare professionals are defined as
medically qualified persons, such as physicians, dentists, pharmacists, nurses
and coroners (see Annex IV, ICH-E2D Guideline).
Herbal medicinal
product
Any
medicinal product, exclusively containing as active ingredients one or more
herbal substances or one or more herbal preparations, or one or more such
herbal substances in combination with one or more such herbal preparations [DIR
2001/83/EC Art 1(30)].
Herbal substances are
all mainly whole, fragmented or cut plants, plant parts, algae, fungi, lichen
in an unprocessed, usually dried, form, but sometimes fresh. Certain exudates
that have not been subjected to a specific treatment are also considered to be
herbal substances. Herbal substances are precisely defined by the plant part
used and the botanical name according to the binominal system [DIR 2001/83/EC
Art 1(31)].
Herbal preparations are
preparations obtained by subjecting herbal substances to treatments such as
extraction, distillation, expression, fractionation, purification,
concentration or fermentation. These include comminuted or powered herbal
substances, tinctures, extracts, essential oils, expressed juices and processed
exudates [DIR 2001/83/EC Art 1(32)].
Homeopathic medicinal
product
Any medicinal product
prepared from substances called homeopathic stocks in accordance with a
homeopathic manufacturing procedure described by the European Pharmacopoeia or,
in the absence thereof, by the pharmacopoeias currently used officially in the
Member States. A homeopathic medicinal product may contain a number of
principles [DIR 2001/83/EC Art 1(5)].
Identified risk
An untoward occurrence for which there is
adequate evidence of an association with the medicinal product of interest (see
ICH-E2F Guideline, Volume 10 of the Rules Governing Medicinal Products in the
EU).
Examples include:
• an adverse reaction adequately demonstrated in
non-clinical studies and confirmed by clinical data;
Guideline on good pharmacovigilance practices (GVP) –
Annex I (Rev 2)
EMA/876333/2011 Rev 2
Page 10/25
•
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)).
See also Risks related to use of a medicinal product, Important
identified risk and Important potential risk, Missing information, Unexpected
adverse reaction
Illegal purposes
See Misuse for illegal
purposes
Immunological medicinal
product
Any medicinal product consisting of vaccines, toxins, serums or
allergen products:
Vaccines, toxins and
serums shall cover in particular agents used to produce active immunity (such
as cholera vaccine, BCG, polio vaccine, smallpox vaccine), agents used to diagnose
the state of immunity (including in particular tuberculin and tuberculin PPD,
toxins for the Schick and Dick Tests, brucellin) and agents used to produce
passive immunity (such as diphtheria antitoxin, anti-smallpox globulin,
antilymphocytic globulin).
Allergen products shall
mean any medicinal product which is intended to identify or induce a specific
acquired alteration in the immunological response to an allergizing agent [DIR
2001/83/EC Art 1(4)].
BCG stands for Bacillus Calmette-Guérin vaccine and PPD for purified
protein derivative.
Immunisation
The process of making a person immune.
For the context of
Considerations P.I, immunisation refers to the process of making a person
immune to an infection.
See also Vaccination
Immunisation anxiety-related
reaction
An adverse event
following immunisation arising from anxiety about the immunisation (see
CIOMS-WHO9).
In this definition
immunisation means the usage (handling, prescribing and administration) of a
vaccine for the purpose of immunising individuals (see CIOMS-WHO9), which in the EU is
preferably referred to as vaccination (in
9 Council for
International Organizations of Medical Sciences (CIOMS). Definition and
application of terms of vaccine pharmacovigilance (report of CIOMS/WHO Working
Group on Vaccine Pharmacovigilance). Genève: CIOMS; 2012.
Guideline on good pharmacovigilance practices (GVP) –
Annex I (Rev 2)
EMA/876333/2011 Rev 2
Page 11/25
the report of CIOMS/WHO
Working Group on Vaccine Pharmacovigilance the terms immunisation and
vaccination are used interchangeably9).
See also Adverse
reaction, Vaccine pharmacovigilance, Vaccination
Immunisation
error-related reaction
An adverse event
following immunisation that is caused by inappropriate vaccine handling,
prescribing or administration and thus by its nature is preventable (see
CIOMS-WHO10).
In this definition
immunisation means the usage (handling, prescribing and administration) of a
vaccine for the purpose of immunising individuals (see CIOMS-WHO10), 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
interchangeably10).
Inappropriate refers to
usage (handling, prescribing and administration) other than what is licensed
and recommended in a given jurisdiction based on scientific evidence or expert
recommendations (see CIOMS-WHO10).
See also Adverse
reaction, Vaccine pharmacovigilance, Vaccination
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 (see ICH-E2F Guideline, Volume
10 of the Rules Governing Medicinal Products in the EU).
What constitutes an
important risk will depend upon several factors, including the impact on the
individual, the seriousness of the risk and 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 (see Annex IV, ICH-E2C(R2) Guideline).
See also Risk-benefit
balance, Identified risk, Potential risk, Safety concern
Important potential
risk
See Important
identified risk and Important potential risk
Incident
A situation
where an event occurs or new information arises, irrespective whether this is
in the public domain or not, in relation to (an) authorised medicinal
product(s) which could have a serious impact on public health.
The incident may be
related to quality, efficacy or safety concerns, but most likely to safety
and/or quality (and possibly subsequent supply shortages). In addition,
situations that do not seem at a first glance to have a serious impact on
public health, but are in the public domain - subject of media attention or
not- and may lead to serious public concerns about the product, may also need
to be considered as incidents. Likewise, other situations which might have a
negative impact on the appropriate use of a medicinal products (e.g. resulting
in patients stop taking their medicine) may fall within the definition of an
incident.
In the
context of this the European Union Regulatory Network Incident Management Plan
for Medicines for Human Use Incident Management Plan, an incident relates to
(a) medicinal product(s) authorised in the EU, irrespective of their route of
authorisation.
10 Council for
International Organizations of Medical Sciences (CIOMS). Definition and
application of terms of vaccine pharmacovigilance (report of CIOMS/WHO Working
Group on Vaccine Pharmacovigilance). Genève: CIOMS; 2012.
Guideline on good pharmacovigilance practices (GVP) –
Annex I (Rev 2)
EMA/876333/2011 Rev 2
Page 12/25
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 time11.
See also Minimum
criteria for reporting
International birth
date (IBD)
The date of the first
marketing authorisation for any product containing the active substance granted
to any company in any country in the world (see Annex IV, ICH-E2C(R2)
Guideline).
Investigational drug
Experimental product
under study or development. This term is more specific than investigational
medicinal product, which includes comparators and placebos (see ICH-E2F
Guideline, Volume 10 of the Rules Governing Medicinal Products in the EU).
See also
Investigational medicinal product
Investigational
medicinal product
An investigational
medicinal product is a pharmaceutical form of an active substance or placebo
being tested or used as a reference in a clinical trial, including products
already with a marketing authorisation but used or assembled (formulated or
packaged) in a way different from the authorised form, or when used for an
unauthorised indication, or when used to gain further information about the authorised
form [Dir 2001/20/EC Art 2(d)].
See also Clinical trial
Labelling
Information on the immediate or outer packaging [DIR 2001/83/EC Art
1(25)].
Medicinal product
Any substance or combination of substances
• presented as having properties for treating or
preventing disease in human beings; or
•
which may be used in or administered to human beings either with a
view to restoring, correcting or modifying physiological functions by exerting
a pharmacological, immunological or metabolic action, or to making a medical
diagnosis [DIR 2001/83/EC Art 1(2)].
Medicinal product
derived from human blood or human plasma
Any
medicinal product based on blood constituents which is prepared industrially by
a public or private establishment, such as a medicinal product including, in
particular, albumin, coagulating factor(s) and immunoglobulin(s) of human
origin [DIR 2001/83/EC Art 1(10)].
11 In the context of a
clinical trial, an individual case is the information provided by a primary
source to describe suspected unexpected serious adverse reactions related to
the administration of one or more investigational medicinal products to an
individual patient at a particular point of time.
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For the
purpose of reporting cases of suspected adverse reactions, the minimum data
elements for a case are: an identifiable reporter, an identifiable patient, an
adverse reaction and a suspect medicinal product (see Annex IV, ICH-E2D
Guideline).
For the purpose of validation of individual case safety reports as
qualifying for reporting in the EU, see Module VI.
See also Individual
case safety report
Missing information
Gaps in knowledge,
related to safety or particular patient populations, which could be clinically
significant.
It is noted that there
is an ICH definition for important missing information, which is: critical gaps
in knowledge for specific safety issues or populations that use the marketed
product (see Annex IV, ICH-E2C(R2) Guideline).
Misuse of a medicinal
product
Situations where the
medicinal product is intentionally and inappropriately used not in accordance
with the authorised product information.
See also Misuse of a
medicinal product for illegal purposes
Misuse of a medicinal
product for illegal purposes
Misuse for illegal
purposes is misuse with the additional connotation of an intention of misusing
the medicinal product to cause an effect in another person. This includes,
amongst others: the sale, to other people, of medicines for recreational
purposes and use of a medicinal product to facilitate assault.
See also Misuse of a
medicinal product
Name of the medicinal
product
The name
which may be either an invented name not liable to confusion with the common
name, or a common or scientific name accompanied by a trade mark or the name of
the marketing authorisation holder [DIR 2001/83/EC Art 1(20)].
The common name is the
international non-proprietary name (INN) recommended by the World Health
Organization, or, if one does not exist, the usual common name [DIR 2001/83/EC
Art 1(21)].
The complete name of
the medicinal product is the name of the medicinal product followed by the
strength and pharmaceutical form.
Newly identified signal
In periodic
benefit-risk evaluation reports, a signal first identified during the reporting
interval, prompting further actions or evaluation (see Annex IV, ICH-E2C(R2)
Guideline).
This definition could
also apply to a previously closed signal for which new information becomes
available in the reporting interval prompting further action or evaluation (see
Annex IV, ICH-E2C(R2) Guideline).
This definition is also applicable to periodic safety update reports.
See also Signal, Closed
signal
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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
[Dir 2001/20/EC Art 2(c)].
Thus, a trial is non-interventional if the following requirements are
cumulatively fulfilled:
•
the medicinal product is 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; and
•
no additional diagnostic or monitoring procedures are applied to the
patients and epidemiological methods are used for the analysis of collected
data (see Volume 10 of the Rules Governing Medicinal Products in the EU,
Questions & Answers Version 10.0).
Non-interventional
studies are defined by the methodological approach used and not by the
scientific objectives. Non-interventional studies include database research or
review of records where all the events of interest have already happened (this
may include case-control, cross-sectional, cohort and other study designs
making secondary use of data). Non-interventional studies also include those
involving primary data collection (e.g. prospective observational studies and
registries in which the data collected derive from routine clinical care), provided
that the conditions set out above are met. In these studies, interviews,
questionnaires and blood samples may be performed as normal clinical practice.
Non-interventional trials do not fall in the scope of Directive
2001/20/EC.
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.
Off-label use
Situations where a
medicinal product is intentionally used for a medical purpose not in accordance
with the authorised product information.
Off-label use includes
use in non-authorised paediatric age categories. Unless specifically requested,
it does not include use outside the EU in an indication authorised in that
territory which is not authorised in the EU.
Ongoing clinical trial
Trial where
enrolment has begun, whether a hold is in place or analysis is complete, but
for which a final clinical study report is not available (see ICH-E2F Guideline,
Volume 10 of the Rules Governing Medicinal Products in the EU).
See also Clinical
trial, Completed clinical trial
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In periodic
benefit-risk evaluation reports, a signal that remains under evaluation at the
data lock point (see Annex IV, ICH-E2C(R2) Guideline).
This definition is also applicable to periodic safety update reports.
See also Signal, Data
lock point
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. Clinical judgement should always be applied.
Package leaflet
A leaflet containing
information for the user which accompanies the medicinal product [Dir
2011/83/EC Art 1(26)].
Periodic safety update
report (PSUR)
Format and content for
providing an evaluation of the risk-benefit balance of a medicinal product for
submission by the marketing authorisation holder at defined time points during
the post-authorisation phase.
In the EU, periodic safety update reports should follow the format
described in Module VII.
Pharmacovigilance
Science and activities
relating to the detection, assessment, understanding and prevention of adverse
effects or any other medicine-related problem (see WHO12).
In line with this
general definition, underlying objectives of pharmacovigilance in accordance
with the applicable EU legislation for 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.
Pharmacovigilance is therefore an activity contributing to the
protection of patients’ and public health.
Pharmacovigilance
system
A system used by the
marketing authorisation holder and by Member States to fulfil the tasks and
responsibilities listed in Title IX of Directive 2001/83/EC and designed to
monitor the safety of authorised medicinal products and detect any change to
their risk-benefit balance [DIR 2001/83/EC Art 1(28d)].
In general, a pharmacovigilance system is a
system used by an organisation to fulfil its legal tasks and responsibilities
in relation to pharmacovigilance and designed to monitor the safety of
authorised medicinal products and detect any change to their risk-benefit
balance.
12 World Health
Organization (WHO). The importance of pharmacovigilance: safety monitoring of
medicinal products. Genève: WHO; 2002.
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A detailed description
of the pharmacovigilance system used by the marketing authorisation holder with
respect to one or more authorised medicinal products [DIR 2001/83/EC Art
1(28e)].
See also
Pharmacovigilance system
Post-authorisation
safety study (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 [DIR 2001/83/EC Art 1(15)].
A post-authorisation
safety study may be an interventional clinical trial or may follow an
observational, non-interventional study design.
See also Clinical
trial, Non-interventional trial
Potential risk
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 (see ICH-E2F Guideline, Volume 10 of the Rules Governing Medicinal
Products in the EU).
Examples include:
• 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 (see ICH-E2F Guideline, Volume 10 of the Rules Governing
Medicinal Products in the EU).
See also Adverse event,
Signal
Quality adherence
Carrying out tasks and
responsibilities in accordance with quality requirements [IR 520/2012 Art
8(3)]. See also Quality requirements
Quality assurance
See Quality control and
assurance
Quality control and
assurance
Monitoring and
evaluating how effectively the structures and processes have been established
and how effectively the processes are being carried out [IR 520/2012 Art 8(3)].
This applies for the purpose of fulfilling quality requirements.
See also Quality
requirements
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Correcting and improving the structures and processes where necessary
[IR 520/2012 Art 8(3)].
This applies for the purpose of fulfilling quality requirements.
See also Quality
requirements
Quality of a pharmacovigilance
system
All characteristics of
the pharmacovigilance system which are considered to produce, according to
estimated likelihoods, outcomes relevant to the objectives of
pharmacovigilance.
See also
Pharmacovigilance system, Quality system of a pharmacovigilance system
Quality objectives
See Quality
requirements
Quality planning
Establishing structures and planning integrated and consistent
processes [IR 520/2012 Art 8(3)].
This applies for the purpose of fulfilling quality requirements.
See also Quality
requirements
Quality requirements
Those characteristics
of a system that are likely to produce the desired outcome, or quality
objectives. See also Pharmacovigilance
system, Quality system of a pharmacovigilance system
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 [IR 520/2012 Art 8(2)].
The quality system is part of the pharmacovigilance system.
See also
Pharmacovigilance system, Quality of a pharmacovigilance system
Reference safety
information
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 (see Annex IV, ICH-E2C(R2) Guideline).
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 (see Annex IV,
ICH-E2C(R2) Guideline).
See also Company core
data sheet, Company core safety information
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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.
Risk-benefit balance
An evaluation of the
positive therapeutic effects of the medicinal product in relation to the risks
[DIR 2001/83/EC Art 1(28a)], i.e. any risk relating to the quality, safety or
efficacy of the medicinal product as regards patients’ health or public health
[DIR 2001/83/EC Art 1(28)].
See also Risks related
to use of a medicinal product
Risk management plan
(RMP)
A detailed description of the risk management system [DIR 2001/83/EC
Art 1(28c)].
To this end, it must
identify or characterise the safety profile of the medicinal product(s)
concerned, indicate how to characterise further the safety profile of the
medicinal product(s) concerned, document measures to prevent or minimise the
risks associated with the medicinal product, including an assessment of the
effectiveness of those interventions and document post-authorisation
obligations that have been imposed as a condition of the marketing
authorisation [IR 520/2012 Art 30].
See also Risk
management system, Risk minimisation activity
Risk management system
A set of
pharmacovigilance activities and interventions designed to identify,
characterise, prevent or minimise risks relating to a medicinal product,
including the assessment of the effectiveness of those interventions [DIR
2001/83/EC Art 1(28b)].
Risk minimisation
activity; synonym: Risk minimisation measure
A public health
intervention intended to prevent or reduce the probability of the occurrence of
an adverse reaction associated with the exposure to a medicine, or to reduce
its severity should it occur.
These activities may
consist of routine risk minimisation (e.g. product information) or additional
risk minimisation activities (e.g. healthcare professional or patient
communications/educational materials).
Risks related to use of
a medicinal product
Any risk relating to
the quality, safety or efficacy of the medicinal product as regards patients’
health or public health and any risk of undesirable effects on the environment
[DIR 2001/83/EC Art 1(28)].
Safety concern
An important identified risk, important potential risk or missing
information.
It is noted that the
ICH definition of safety concern is: an important identified risk, important
potential risk or important missing information, i.e. includes the qualifier
“important” in relation to missing information (see Annex IV, ICH-E2C(R2)
Guideline). The ICH-E2E Guideline (see 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.
See also Important
identified risk and Important potential risk, Missing information
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An adverse reaction
which results in death, is life-threatening, requires in-patient
hospitalisation or prolongation of existing hospitalisation, results in
persistent or significant disability or incapacity, or is a congenital
anomaly/birth defect [DIR 2001/83/EC Art 1(12)].
Life-threatening in
this context refers to a reaction in which the patient was at risk of death at
the time of the reaction; it does not refer to a reaction that hypothetically
might have caused death if more severe (see Annex IV, ICH-E2D Guideline).
Medical and scientific
judgement should be exercised in deciding whether other situations should be
considered serious reactions, such as important medical events that might not
be immediately life threatening or result in death or hospitalisation but might
jeopardise the patient or might require intervention to prevent one of the
other outcomes listed above. Examples of such events are intensive treatment in
an emergency room or at home for allergic bronchospasm, blood dyscrasias or
convulsions that do not result in hospitalisation or development of dependency
or abuse (see Annex IV, ICH-E2D Guideline).
Any suspected
transmission via a medicinal product of an infectious agent is also considered
a serious adverse reaction.
See also Adverse
reaction
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 [IR 520/2012 Art 19(1)].
For the purpose of
monitoring data in the EudraVigilance database, only signals related to an
adverse reaction shall be considered [IR 520/2012, Art 19(1)].
For the purpose of
Section 16.2 of the periodic benefit-risk evaluation report, signals relate to
adverse effects (see Annex IV, ICH-E2C(R2) Guideline).
See also Validated signal, Newly identified signal, Closed signal,
Ongoing signal, Signal management process, Adverse reaction
Signal management
process
Includes the following
activities: signal detection, signal validation, signal confirmation, signal
analysis and prioritisation, signal assessment and recommendation for action
[IR 520/2012 Art 21(1)].
It therefore is 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, literature information or other data sources, there are new
risks causally associated with an active substance or a medicinal product or
whether known risks have changed.
See also Signal
validation
Signal validation
Process of evaluating
the data supporting a 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 [IR 520/2012 Art 21(1)].
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See also Validated
signal
Solicited sources of
individual case safety reports
Organised data
collection systems, which include clinical trials, registries,
post-authorisation named-patients use programmes, other patient support and
disease management programmes, surveys of patients or healthcare providers or
information gathering on efficacy or patient compliance. For the purpose of
safety reporting, solicited reports should not be considered spontaneous but
classified as individual case safety reports from studies and therefore should
have an appropriate causality assessment by a healthcare professional or the
marketing authorisation holder (see Annex IV, ICH-E2D).
See also Clinical
trial, Post-authorisation safety study, Non-interventional trial
Spontaneous report,
synonym: Spontaneous notification
An unsolicited
communication by a healthcare professional or consumer to a company, regulatory
authority or other organisation (e.g. the World Health Organization, a regional
centre, a poison control centre) that describes one or more adverse reactions
in a patient who was given one or more medicinal products and that does not
derive from a study or any organised data collection scheme (see Annex IV,
ICH-E2D).
In this context, an adverse reaction refers to a suspected adverse
reaction.
Stimulated reporting can occur in certain
situations, such as after a direct healthcare professional communication
(DHPC), a publication in the press or questioning of healthcare professionals
by company representatives, and adverse reaction reports arising from these
situations are considered spontaneous reports (see Annex IV, ICH-E2D), provided
the report meets the definition above. Reporting can also be stimulated by
invitation from patients’ or consumers’ organisations to their members.
Reporting made in the context of early post-marketing phase vigilance (EPPV),
e.g. in Japan, is also considered stimulated reporting.
See also Adverse
reaction
Stimulated reporting
See Spontaneous report
Substance
Any matter irrespective
of origin which may be human (e.g. human blood and human blood products),
animal (e.g. micro-organisms, whole animals, parts of organs, animal
secretions, toxins, extracts, blood products), vegetable (e.g. micro-organisms,
plants, part of plants, vegetable secretions, extracts), chemical (e.g.
elements, naturally occurring chemical materials and chemical products obtained
by chemical change or synthesis) [DIR 2001/83/EC Art 1(3)].
Summary of product
characteristics (SmPC)
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 (based on A Guideline on Summary of Product
Characteristics, Volume 2C of the Rules Governing Medicinal Products in the
EU).
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The patients who might
be treated with the medicinal product in accordance with the indication(s) and
contraindications in the authorised product information.
Target population
(vaccine); synonym: Vaccine target population
Persons who might be
vaccinated in accordance with the indication(s) and contraindications in the
authorised product information and official recommendations for vaccinations.
Traditional herbal
medicinal product
A herbal medicinal
product that fulfils the conditions laid down in Article 16a(1) of Directive
2001/83/EC [DIR 2001/83/EC Art 1(29)], i.e.
(a)
it has (an)indication(s) exclusively appropriate to traditional herbal
medicinal products which, by virtue of their composition and purpose, are
intended and designed for use without the supervision of a medical practitioner
for diagnostic purposes or for prescription or monitoring of treatment;
(b) it is exclusively for administration in
accordance with a specified strength and posology;
(c) it is an oral, external and/or inhalation
preparation;
(d) the period of traditional use as laid down in
Article 16c(1)(c) has elapsed;
(e)
the data on the traditional use of the medicinal product are
sufficient; in particular the product proves not to be harmful in the specified
conditions of use and the pharmacological effects or efficacy of the medicinal
product are plausible on the basis of long-standing use and experience [DIR
2001/83/EC Art 16a].
Regarding (d), the
product must have been in medicinal use throughout a period of at least 30
years, including at least 15 years within the EU (see DIR 2001/83/EC Art 16c(c)
and European Commission Questions & Answers Document on Registration of
Traditional Herbal Medicinal Products, 2011).
See also Herbal
medicinal product
Unexpected adverse
reaction
An adverse reaction,
the nature, severity or outcome of which is not consistent with the summary of
product characteristics [DIR 2001/83/EC Art 1(13)]13.
This includes
class-related reactions which are mentioned in the summary of product
characteristics (SmPC) but which are not specifically described as occurring
with this product. For products authorised nationally, the relevant SmPC is
that authorised by the competent authority in the Member State to whom the
reaction is being reported. For centrally authorised products, the relevant
SmPC is the SmPC authorised by the European Commission. During the time period
between a CHMP opinion in favour of granting a marketing authorisation and the
Commission decision granting the marketing authorisation, the relevant SmPC is
the SmPC annexed to the CHMP opinion.
See also Summary of
product characteristics
Upper management
Group of persons in charge of the highest executive management of an
organisation.
13 For investigational
medicinal products, an unexpected adverse reaction is an adverse reaction, the
nature or severity of which is not consistent with the applicable product
information (e.g. the investigator’s brochure for an unauthorised
investigational product or the summary of product characteristics for an
authorised product) [Dir 2001/20/EC Art 2(p)].
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Membership of this
group is determined by the governance structure of the organisation. While it
is envisaged that the upper management usually is a group, the head of the
organisation is the one person at the top of the organisation with ultimate
responsibility for ensuring that the organisation complies with relevant
legislation.
Vaccination
The administration of a vaccine with the aim to produce immune
response.
See also Immunisation
Vaccination failure
Vaccination failure due to actual vaccine failure or failure to
vaccinate (see CIOMS-WHO14).
Vaccination failure may
be defined based on clinical endpoints or immunological criteria, where
correlates or surrogate markers for disease protection exist. Primary failure
(e.g. lack of seroconversion or seroprotection) needs to be distinguished from
secondary failure (waning immunity) (see CIOMS-WHO14).
See also Vaccine
failure, Failure to vaccinate
Vaccine
See Immunological
medicinal product
Vaccine failure
Confirmed or suspected vaccine failure.
Confirmed clinical vaccine failure
Occurrence of the
specific vaccine-preventable disease in a person who is appropriately and fully
vaccinated taking into account the incubation period and the normal delay for
the protection to be acquired as a result of immunisation (see CIOMS-WHO15).
Suspected clinical vaccine failure
Occurrence of disease
in an appropriately and fully vaccinated person, but the disease is not confirmed
to be the specific vaccine-preventable disease, e.g. disease of unknown
serotype in a fully vaccinated person (based on CIOMS-WHO15).
Confirmed immunological vaccine failure
Failure of the
vaccinated person to develop the accepted marker of protective immune response
after being fully and appropriately vaccinated, as demonstrated by having
tested or examined the vaccinated person at an appropriate time interval after
completion of immunisation (based on CIOMS-WHO15).
Suspected immunological vaccine failure
Failure of
the vaccinated person to develop the accepted marker of protective immune
response after being fully and appropriately vaccinated, but with the testing
or examination of the vaccinated person done at an inappropriate time interval
after completion of immunisation (based on CIOMS-WHO15).
14 Council for
International Organizations of Medical Sciences (CIOMS). Definition and
application of terms of vaccine pharmacovigilance (report of CIOMS/WHO Working
Group on Vaccine Pharmacovigilance). Genève: CIOMS; 2012.
15 Council for
International Organizations of Medical Sciences (CIOMS). Definition and
application of terms of vaccine pharmacovigilance (report of CIOMS/WHO Working
Group on Vaccine Pharmacovigilance). Genève: CIOMS; 2012.
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For interpreting what
means appropriately vaccinated, consider the explanatory note for Immunisation
error-related reaction.
See also Vaccination
failure
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 immunisation (see CIOMS-WHO16).
In this definition,
immunisation means the usage of a vaccine for the purpose of immunising
individuals (see CIOMS-WHO16), 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
interchangeably16). 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-WHO16).
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-WHOf6 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 (see CIOMS-WHO16).
See also Adverse event, Immunisation anxiety-related reaction,
Immunisation error-related reaction, Vaccine product-related reaction, Vaccine
quality defect-related reaction, Vaccination
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-WHO17).
In this definition
immunisation means the usage (handling, prescribing and administration) of a
vaccine for the purpose of immunising individuals (see CIOMS-WHO17), 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
interchangeably17).
See also Adverse
reaction, Vaccine pharmacovigilance
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-WHO18).
In this definition
immunisation means the usage (handling, prescribing and administration) of a
vaccine for the purpose of immunising individuals (see CIOMS-WHO18), which in the EU is
preferably referred to as vaccination (in
16 Council for International
Organizations of Medical Sciences (CIOMS). Definition and application of terms
of vaccine pharmacovigilance (report of CIOMS/WHO Working Group on Vaccine
Pharmacovigilance). Genève: CIOMS; 2012.
17 Council for
International Organizations of Medical Sciences (CIOMS). Definition and
application of terms of vaccine pharmacovigilance (report of CIOMS/WHO Working
Group on Vaccine Pharmacovigilance). Genève: CIOMS; 2012.
18 Council for
International Organizations of Medical Sciences (CIOMS). Definition and
application of terms of vaccine pharmacovigilance (report of CIOMS/WHO Working
Group on Vaccine Pharmacovigilance). Genève: CIOMS; 2012.
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the report of CIOMS/WHO
Working Group on Vaccine Pharmacovigilance the terms immunisation and
vaccination are used interchangeably18).
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 (see CIOMS-WHO18).
See also Adverse
reaction, Vaccine pharmacovigilance
Valid individual case
safety report
See Individual case
safety report
Validated signal
A signal where the
signal validation process of evaluating the data supporting the detected signal
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 [based on IR 520/2012 Art 21(1)].
See also Signal
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