GOOD PHARMACOVIGILANCE
PRACTICES
SOURABH KOSEY
ASSOCIATE PROFESSOR
DEPT. OF PHARMACY PRACTICE
ISF COLLEGE OF PHARMACY
WEBSITE: - WWW.ISFCP.ORG
EMAIL: SOURABHKOSEY@GMAIL.COM
ISF College of Pharmacy, Moga
Ghal Kalan,nGT Road, Moga- 142001, Punjab, INDIA
Internal Quality Assurance Cell - (IQAC)

OUTLINE
 DEFINITIONS
 HISTORY
 PHARMACOVIGILANCE PROCESS
 WHAT IS GVP?
 METHODS
 DEVELOPMENTS IN PV
 PvPI
 REFRENCES
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 PHARMACOVIGILANCE
The
World Health Organization (WHO)
defines Pharmacovigilance as
“the science and activities
relating to the detection,
assessment, understanding and
prevention of adverse effects or
any other drug-related problem.”
 ADVERSE DRUG REACTION
According to WHO “ADR is a
response to a drug which is
noxious and unintended, and
which occurs at doses normally
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HISTORY OF
PHARMACOVIGILANCE
 1848
The Lancet started collecting notifications of side
effects caused by use of anaesthesia.
 1906
US Federal and Food Act was implemented stating
that pharmaceuticals should be ‘pure’ & free from
‘contamination’.
 1937
In USA 107 lethal cases were reported after
diethylene glycol was mistakenly used as solvent for
sulphanilamides.
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 1959-61
Reports of foetal abnormalities after the use of drug
thalidomide.
 1962
USA revised law requiring to prove safety and
efficacy of drug before issuing marketing
authorization.
 1967
WHO’s International Drug Monitoring programme
was launched.
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WHAT IS GPV (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 and medicines
regulatory authorities in EU Member States.
 Our knowledge of a drug’s adverse
reactions can be increased by various
means, including spontaneous reporting,
intensive monitoring and database studies.
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METHODS
1) CLINICAL TRIAL DATA
COLLECTION
 Main method currently used to gather information
on a drug in the pre-marketing phase.
 Pre-marketing clinical trials can be divided into
three phases.
 These are considered to be the most rigorous
approach to determining whether a cause-effect
relationship exists between a treatment and an
outcome.
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 This study design is not optimal due to the limited
number of patients participating, it is generally not
possible to identify ADRs that occur only rarely.
 Moreover short duration of clinical trials makes it
difficult to detect ADRs with a long latency.
 Another limitation of clinical trials is the population in
which a drug is tested i.e characteristics of the
participants do not always correspond to the
characteristics of the population in which it will later
be used; consequently, it may be difficult to
extrapolate the results obtained from clinical trials to
the population at a larger scale.
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2)SPOTANEOUS REPORTING
 In 1961, a letter from the Australian physician WG
McBride was published in Lancet. In this letter, he
shared his observation that babies whose mothers
had used thalidomide during pregnancy were born
with congenital abnormalities more often than
babies who had not been exposed to thalidomide in
utero.
 In the years to come it became evident that
thousands of babies had been born with limb
malformations due to the maternal use of
thalidomide.
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 In order to prevent a similar disaster from
occurring, systems were set up all over the world
with the aim of regulating and monitoring the safety
of drugs.
 Thus, Spontaneous reporting systems (SRS)
were
created and these have become the primary
method of collecting post-marketing information
on the safety of drugs.
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 This system enables physicians and, increasingly more
often, pharmacists and patients to report suspected
ADRs to a pharmacovigilance centre.
 The task of the pharmacovigilance centre is to collect
and analyse the reports and to inform stakeholders of
the potential risk when signals of new ADRs arise.
 Also used by various industries for reporting of their
drugs.
 Possible to monitor all drugs on the market throughout
their entire life cycle at a relatively low cost.
 The main criticism of this approach is the potential for
selective reporting and underreporting
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3 DATA MINING IN SPONTANEOUS
REPORTING
 The term ‘data mining’ refers to the principle of
analysing data from different perspectives and
extracting the relevant information.
 Approaches of data mining are currently in use are
Proportional reporting ratios (PPRs), compare the
proportion of reports for a specific ADR reported for a
drug with the proportion for that ADR in all other
drugs.
 The Bayesian confidence propagation neural network
(BCPNN) method is used to highlight dependencies in
a data set. This approach uses Bayesian statistics
implemented in a neural network architecture to
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 WHO Collaborating Centre for International Drug
Monitoring uses this method for data mining.
 A related approach is the Multi-Item Gamma
Poisson Shrinker (MGPS) used by the FDA for data
mining of their spontaneous report’s database. The
MGPS algorithm computes signal scores for pairs,
and for higher-order (e.g. triplet, quadruplet)
combinations of drugs and events that are
significantly more frequent than their pair-wise
associations would predict
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4)INTENSIVE MONITORING
 In the late 1970s and early 1980s a new form of
active surveillance was developed in New Zealand
(Intensive Medicines Monitoring Programme) and
the UK (Prescription Event Monitoring).
 These intensive monitoring systems use
prescription data to identify users of a certain drug.
 The prescriber of the drug is asked about any
adverse event occurring during the use of the drug
being monitored. These data are collected and
analysed for new signals.
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 It is unaffected by the kind of selection and
exclusion criteria that characterise clinical trials,
thereby eliminating selection bias.
 Another strength of this methodology is that it is
based upon event monitoring and is therefore
capable of identifying signals for events that were
not necessarily suspected as being ADRs of the
drug being studied.
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This approach, however, also hasThis approach, however, also has
recognised limitations :-recognised limitations :-
a)a) The proportion of adverse effects thatThe proportion of adverse effects that
go unreported is unknown.go unreported is unknown.
b)b) It produces reported event ratesIt produces reported event rates
rather than true incident ratesrather than true incident rates
c)c) The true background incidence forThe true background incidence for
events is not known.events is not known.
 In European commission consultationIn European commission consultation
‘Strategy to better protect public‘Strategy to better protect public
health by strengthening andhealth by strengthening and
rationalising EU pharmacovigilance’rationalising EU pharmacovigilance’
intensive monitoring is mentioned asintensive monitoring is mentioned as
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5)DATABASE STUDIES
 The General Practice Research Database (GPRD) and
the PHARMO Record Linkage System are two major
European database used for ADR reporting.
 GPRD
 Virtually all patient care in the UK is coordinated by the
general practitioner (GP), and data from this source
provide an almost complete picture of a patient, his
illnesses and treatment.
 In any given year, GPs, who are members of the GPRD,
collect data from about 3 million patients and ADR
reporting is done.
 There have been over 250 publications in peer-reviewed
journals using the GPRD.
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 PHARMO
 In the early 1990s, the PHARMO system of record linkage
was developed in The Netherlands.
 PHARMO links community pharmacy and hospital data
within a specific region on the basis of patient birth date,
gender and GP code.
 The system now includes drug-dispensing records from
community pharmacies and hospital discharge records of
about 2 million people in the Netherlands.
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 The data collection is longitudinal and goes back to
1987.
 The system has well-defined denominator
information that allows incidence and prevalence
estimates and is relatively cheap because existing
databases are used and linked.
 The PHARMO database is used for follow-up
studies, case-control studies and other analytical
epidemiological studies for evaluating drug-induced
effects.
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6.PERIODIC SAFETY UPDATE REPORTS(PSUR)

Pre marketing clinical trials may not be sufficient to reflect
the product safety profile.
 Therefore medically advanced countries impose the
“post marketing drug safety monitoring period ” on new
drugs.
License holders shall proactively collect post marketing
safety data, prepare PSUR and submit them to the health
authority.
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 According to the “regulation of medical products
under safety monitoring” ,if pharmaceutical companies
fail to submit PSUR as required , then the health
authority may reassess the safety of the concerned
product.
 The last PSUR should be submitted before the
expiration of the drug safety monitoring period.
The “summary bridging report” provides summarized
information of the PSURs.
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NARANJO ALGORITHM
For assessing the causality –
- Definite = ≥9
- Probable = 5-8
- Possible = 1-4
- Doubtful = ≤ 0
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Hartwig and Seigels scale
For assessing the severity-
1.Mild ADRs-are self limiting and do not
contribute
to prolongation of length of hospital stay.
2.Moderate ADRs- require therapeutic
intervention or hospital admission or prolonged
hospital stay by at least one day .
3.Severe ADRs- life threatening, requiring
intensive medical care or produce disability or lead
to death.
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DEVELOPMENTS IN PV
 USA
 In February 2007, on the basis of the IOM report, the
FDA announced several initiatives designed to
improve the safety of prescription. These initiatives
fall into four main categories. These are :-
i. Increasing the resources for drug safety activities &
perceiving the agency as being overly dependent on
industry funding.
ii. Reform new authority for the FDA.
iii. Improvement of post-marketing surveillance.
iv. changes in the FDA management practices and
safety supervision are necessary
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 In May 2007, the U.S. senate passed its version of
reform for the FDA. The senate proposed that the
Prescription Drug User Fee Act, which allows the
pharmaceutical industry to pay money directly to the
FDA, should increase their payments to the FDA by
close to U.S. 400 million dollars.
 EUROPE
 In 2005, a document was drafted by the Heads of the
Medicines Agencies called ‘Implementation of the
Action Plan to Further Progress the European Risk
Management Strategy’.
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 The Yellow Card Scheme is the UK system for
collecting information on suspected adverse drug reactions
(ADRs) to medicines. The scheme allows the safety of the
medicines and vaccines that are on the market to be
monitored.
 Founded in 1964 after the thalidomide disaster, and was
developed by Bill Inman.
 It is run by the Medicines and Healthcare Products
Regulatory Agency (MHRA) and the Commission on
Human Medicines (CHM). Suspected ADRs are collected
on all licensed medicines and vaccines, from those issued
on prescription to medicines bought over the counter from a
pharmacist or supermarket.
 The Scheme also includes all herbal preparations and
unlicensed medicines. ADRs can be reported by any
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 The sort of ADRs that should be reported are:
i. ADRs that have caused death or a serious illness
ii. Any ADR, however minor, if associated with a new medicine
or one that is under continued monitoring (highlighted in the
British National Formulary (BNF) with a ▼ black triangle)
iii. Any ADR, however minor, if associated with a child (under 18
years of age) or in pregnancy
 Yellow Cards are available from pharmacies and a few are
presented near the back of the BNF as tear-off pages, copies
may also be obtained by telephoning +44 (0) 808 100
3352.The scheme provides forms that allow members of the
public to report suspected side effects, as well as health
professionals.
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 Officially started on 23 November 2004 at new Delhi.
 Pharmaceutical industry in India is valued at 90,000crore
and is growing at the rate of 12-14% per annum.
 Total export of Pharmacy products is to the extent of
40,000crore.
 India is now being recognized as the “global pharmacy of
generic drugs”
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India is also emerging rapidly as a hub of global clinical
trials & destination for drug discovery and development.
In a vast country like India with a population of over1.2
billion with vast ethnic variability ,different disease
prevalence patterns , practice of different systems of
medicines, different SES , it is important to have robust
Pharmacovigilance and drug safety monitoring
programmes.
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 PVPI is under control of-
1.CDSCO(Central Drugs Standard
Control Organization)
2.directorate general of health
services
3.Indian Pharmacopeia
Commission (Ghaziabad)
The programme is conducting by NCC(National
Coordinating Centre) .
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Goals and objectives-
Goal- to ensure that the benefits of use of medicine
outweighs the risks.
Objectives-
1. To monitor ADRs .
2.To create awareness among health care professionals
about ADRs.
3. To monitor benefit-risk profile of medicines.
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4. Generate independent ,evidence based
recommendations.
5. Support the CDSCO.
6. Communicate findings with all stake holders.
7. Create a national centre.
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PvPI is administered and monitored by the following committees:-
1.Steering Committee
2.Strategic Advisory Committee
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EUROPEAN UNION GOOD
PHARMACOVIGILANCE PRACTICES
 ....GPVPEU P.pdf
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