Definitions and terminologies

Pharmacovigilance
• The science and activities relating to the
detection, assessment, understanding and
prevention of adverse effects or any other
drug-related problem
• Adverse Event

Medical occurrence temporally associated with the

use of a medicinal product, but not necessarily
causally related

• Adverse Drug Reaction

A response to a drug which is noxious and

unintended, and which occurs at doses normally
used in man for the prophylaxis, diagnosis, or
therapy of disease, or for the modifications of
physiological function'. ADR are always related to
the drug
• Serious Adverse Event or Reaction

Any untoward medical occurrence that at any

dose;
– Results in death
– Or is life threatening
– Requires inpatient hospitalization or prolongation
of existing hospitalization
– Results in persistent of significant disability or
incapacity
– Congenital abnormality
– Medically important event
Non-serious ADRs

• Cases of non-serious ADRs are not normally

reportable on an expedited basis. The
spontaneous reports of non-serious ADRs
should be reported in the periodic safety
update report.
• Signal

Possible causal relationship between

adverse event and drug previously
unknown or incompletely documented
More than one report is needed.
Depending on:
– Quality of the information
– Seriousness of the event
 Valid case report

• A case is considered to be a valid case only

if it includes the “Minimum Safety
Information”(MSI) i.e.
A suspected medicinal product
A reaction/event
An identifiable reporter
An identifiable patient
• Affiliate

Any individual or entity related by employment or organizational

structure to the applicant, including all subsidiaries, whether
domestic or foreign.

 License Partner

A company with which a contractual relationship has been entered

into which permits the use of patents, trademarks, technology,
proprietary processes, or other intellectual property. Typically, for
purposes here, these agreements allow each company to conduct
research on or market the same product, or the same
pharmacologically active entity but in different dosage form or for
different indications. Two or more companies may market the same
product in the same or different countries
 SDEA
• Safety data Exchange Agreements.
It is a controlled document to be shared between
partners to be clearly communicate the process
for exchange of safety information.
-Accounts for the requirements of expediting
reporting.
-It includes explicit licensing/contractual
agreements specify the process for exchange of
information.
-Process should be in place to avoid duplicate
reporting.
 Cont..
• Regulatory authority timeline may not be adjusted to
accommodate safety data exchange between partners.
• Required timely exchange of reports to ensure both the
parties are meeting regulatory timelines.
• Volume 9A- The European commission guidance
document on pharmacovigilance (PV) states that the
reporting clock date is set to ‘0’ when ever marketing
authorization company or any company with a
contractual arrangement with MAH gets information
about adverse event.
 Day (0) Zero

– Day zero otherwise call as CST (clock start

time):
– It’s the day the case report was first identified
by the sponsor/affiliate/licensee/or any
member who is working for the sponsor .
-Fax, telephone, postal, voice mail etc.
 Reporters
• Consumer
A person who is not a healthcare professional
such as a patient, lawyer, friend or relative/
parents/ children of a patient.
• Health care professional
Medically qualified person
ICSR

It is a standard way to capture the information needed to support the

reporting of adverse events, product complaints or consumer complaints
associated with the use of medicinal products.

• An individual case safety report can originate from a multitude of sources,

such as:

• 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 object of ascertaining its
(their) safety and/or efficacy
• Interventional Trial
An interventional clinical trial is any research study that prospectively
assigns people to one or more health-related interventions (e.g.,
preventive care, drugs, surgical procedures, behavioral treatments, etc.) to
evaluate their effects on health-related outcomes. (CIOMS VII) .
• 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 authorization. The
assignment of the patient to a particular therapeutic strategy in 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.
• Literature
Denotes published articles/abstracts in scientific and
medical journals and unpublished manuscripts involving
adverse events which appear as case reports or from
formal clinical studies in which there is an identifiable
patient.
• Named-Patient Program
The use of a medicinal product to treat patients for whom
conventional therapies have failed, or for whom no other
drug exists. This procedure is used with very sick individuals
who have no other treatment options available and often,
case-by-case approval must be obtained from the
regulatory authority
• Registry
A registry is a list of patients presenting with the same characteristic(s). This
characteristic can be a disease (disease registry) or a specific exposure (drug
registry). Both types of registries, which only differ by the type of patient data of
interest, can collect a battery of information using standardized questionnaires in a
prospective fashion.
Note: Reporting requirements for case reports from a registry differ depending on
the design of the registry (e.g. registry is considered as interventional, non-
interventional, or spontaneous), as well as local country reporting requirements

 Regulatory authority
Any competent regulatory authority or other governmental body having the power
to regulate and responsible for granting any Regulatory Approval.
 Types of reports
• Solicited Reports
These are reports that are derived from organized data collection systems,
which include clinical trials, post-authorization studies, studies in claims
data, registries, post-approval named patient use programs, other patient
support and disease management programs, surveys of patients or
healthcare providers, or information gathering on efficacy or patient
compliance. These are reports that are derived during planned contacts
and active solicitation of information from patients, healthcare
professionals, or organizations.

 Spontaneous
An unsolicited communication to a company, regulatory authority, or
other organization that describes an adverse reaction in a patient given
one or more medicinal products and which does not derive from a study
or any organized data collection scheme
• Blinding
A procedure in which one or more parties to the trial
are kept unaware of the treatment assignment(s).
Single-blinding usually refers to the subject(s) being
unaware, and double-blinding usually refers to the
subject(s), investigator(s), monitor, and, in some cases,
data analyst(s) being unaware of the treatment
assignment(s).
In relation to an investigational medicinal product,
blinding shall mean the deliberate disguising of the
identity of the product. Unblinding shall mean the
disclosure of the identity of the blinded products.
• National Competent Authority (NCA)
An authority within the EEA (European Economic Area)
including the EMEA and the European Commission
responsible for the clinical trial and granting of marketing
authorizations for medicinal products and the
supervision of marketing of such products in accordance
with the relevant laws and regulations established under
Community law.
• Marketing Authorization Holder (MAH)
An organization holding a valid marketing authorization
for a medicinal product independent of the authorization
procedure of this medicinal product.
• Causality
Determination of whether there is a reasonable
possibility that the product is etiologically related to
the adverse experience.
• CIOMS 1 form
This is a form with standardized elements and
formatting for reporting adverse events. It was agreed
by the Council for International Organizations of
Medical Sciences (CIOMS) in collaboration with WHO.
Prior to finalization, the form was pretested in a two-
year pilot project involving seven manufacturers and
some 40 affiliates.
• Coding
The process of selecting terms and codes from
a standardized dictionary for a given verbatim
term (i.e. suspect drug, concomitant drug,
adverse events. Indication, medical history,
laboratory tests, etc.).
• Expected/Listed vs. Unexpected/Unlisted

• Expected
An adverse reaction, the nature, or severity of which is consistent with the
applicable product information (i.e. local labeling/prescribing information).

• Listed
Listed or listedness refers to the fact that an adverse reaction is “listed” in the
Company Core Safety Information (CCSI) of the concerned product.
The CCSI, which is embedded in the Company Core Data Sheet (CCDS) forms the
basis for determining whether an adverse reaction is already listed or is still
unlisted (listed and unlisted are terms that are introduced to distinguish them
from the usual terminology of expectedness, which is used in association with the
authorized reference safety information (e.g. SPC, US PI).
Listedness is used to classify adverse events in the PSUR.
• Unexpected
An ADR whose nature, severity, specificity, or outcome is not consistent
with the term or description used in the local/regional product labeling or
other applicable product information (e.g. Investigator’s Brochure for an
unapproved investigational medicinal product, Package Insert or Summary
of Product Characteristics) should be considered unexpected. (ICH E2A,
E2D )

 Unlisted
An adverse reaction which is not specifically included as a suspected
adverse effect in the company care safety information (CCSI). This includes
an adverse reaction whose nature, severity, specificity or outcome is not
consistent with the information in the CCSI. It also includes class-related
reactions which are mentioned in the CCSI but which are not specifically
described as occurring with this product. (Volume 9a)
 Expedited Report and Aggregate
Report
• Expedited Report
An individual case safety report (ICSR) that is required
to be submitted to a regulatory authority in either a 7
or 15 calendar-day time frame, or to other recipients in
such a time frame so as to enable them to fulfill 7 or 15
calendar-day reporting timeframes.
 Aggregate Report
A regulatory required periodic or ad hoc report that
provides a succinct narrative summary and analysis of
the risk-benefit balance for an individual product or a
safety issue.
 What is follow up report?

Follow-up is the process of obtaining additional

information relevant to a case report, as necessary.
Follow-up should be conducted on any report where
one or more of the minimum criteria for a valid case
report is missing, to seek medical confirmation of a
report initially received from a non-HCP, to obtain
missing information in order to gain a complete and
comprehensive understanding of the facts of the case,
to learn the progress and outcome of a case, or to
determine the outcome of a pregnancy.
Newly received information about a case may be
considered as ‘significant’, or ‘non-significant’
• MedWatch Form 3500A
This is the official form which manufacturers
must use for reporting adverse events and
product problems to the FDA for drugs,
biologics, and devices. For reports originating
outside the United States, the CIOMS I form
may be used.
• Misuse of drug
Refers to situations where the medicinal product is
intentionally and inappropriately used not in accordance
with the prescribed or authorized dose, route of
administration and/or indication(s) or where a prescription
only medicinal product was used without a prescription.
• Abuse
Abuse is a type of drug abuse which refer to irregular or
regular, intentional excessive of a medicinal product and is
therefore accompanied by harmful effects.
• Occupational exposure
The exposure to a medicinal product for human use as a
result of one's occupation. This includes the occurrence of
an adverse event or adverse reaction due to inadvertent or
accidental exposure to an active ingredient and/or
excipients during the manufacturing process of a finished
dosage form.
• Overdose
Refers to the administration of a quantity of a
medicinal product given per administration or
per day, which is above the maximal
recommended dose according to the
authorized product information. This shall also
take into account cumulative effects due to
overdose.
• Suspect drug
If there is a reasonable possibility that the adverse event might have
occurred because of the drug which was administered then that drug
would be considered as a suspect drug.

• Concomitant medication
Concomitant medication is any medication (except medication considered
as suspect) taken around the same time that the adverse event occurred.

• Past drug therapy

Past drug therapies are medications which were discontinued prior to the
onset of the adverse event(s). Medical knowledge should be applied in
exceptional circumstances.

• Interacting drug
All interacting drugs are considered to be suspect drugs. Thus, there must
be at least two suspect drugs for drug interaction and both have to be
considered as suspect drugs.
• Nullification of an ICSR:

The process of indicating to the regulatory authorities

that a previously documented case report should be
considered completely void. The case is thus removed
from the company safety database.

• Suppression of a case:

It is the logical deletion of the case from the safety

database, thus this case report remains available for
auditing purpose and an be unsuppressed if needed.
 Off label use
• Off label use refer to use of medicinal product
which is not recommended as per the local
label.

• Should ADRs associated with off-label use of

medicinal products be reported ?
 Questions
1. Is an intern a HCP ?
2. Pfizer is the sponsor and is having an SDEA
agreement with GSK in Japan. A physician got
the information about a patient (with all the
four valid information) on 24th Jan 2012, the
physician in turn inform the sales representative
of GSK on 26th Jan 2012. Sales representative
inform GSK on 27th of Jan 2012. What is the
CST?
3. What is the difference between nullification and
suppression of an ICSR ?