History of Pharmacovigilance

HISTORY AND
DEVELOPMENT OF
PHARMACOVIGILANCE
DR. RAMESH BHANDARI
ASST. PROFESSOR
DEPARTMENT OF PHARMACY PRACTICE
KLE COLLEGE OF PHARMACY, BELAGAVI

By Dr. Ramesh Bhandari
History of Pharmacovigilance
In 1901, in USA: 13 children died from contaminated diphtheria antitoxin
due to which passed Biological Control Act 1902 – ensure purity and safety of
serum, vaccines and other products.
In 1937 in USA: 105 people died including 35 children due to new liquid
formulation (raspberry flavoured elixir) of anti-infective sulphanilamide. (Tablets
and powder was used before for streptococcal infections)
due to which The federal food, drug and cosmetics act (FDCA) was enacted in
1938 which began to examine the risk-benefit profile of medicinal products.
(required proof of safety through NDA)

Gradual increase in regulatory authority:
Durham-Humphrey Amendment of 1951 (FDCA amendment
1951) – separation of drugs into 2 types – drugs could be used
without the physician assistance (named over the counter drugs)
and drugs needing physician assistance.

THALIDOMIDE TRAGEDY:
Late 1950s and early 1960s – changed focus of drug safety from reactive to
proactive (mandates safety surveillance before marketing as well as post
marketing pharmacovigilance.)
1956-1961 used thalidomide in 20 different countries as sleeping pill
(hypnotic) and antiemetic in pregnant women. (but not approved for use in
USA because of its delayed NDA)
Late 1961 and early 1962 reports of various limb deformities (Phocomelia)
from Europe began.

POST THALIDOMIDE EVOLUTION:
- Necessity to monitor drug products for efficacy and safety increases.
- Regulatory changes following thalidomide tragedy:
Kefauver-Harris Amendments:
* Required affirmative approval from the FDA before a product could be
marketed. (21 CFR Part 314)
* Mandatory IND process permitting FDA monitoring of testing, transportation,
and distribution (21 CFR part 312)
* Mandate registration of subjects exposed during pre-clinical and clinical testing
(21 CFR part 50)

Kefauver-Harris Amendments:
* Established 3 separate phases of clinical trial to prove efficacy (21
CFR part 312)
* Required uniformly formatted drug labelling (21 CFR part
201.57)
* Established good manufacturing practices (21 CFR part 210)
* Regular post marketing communication with FDA on experience
with the drugs (all spontaneous reporting, analysis of medical
literature on product)

Origin of Pharmacovigilance
Pharmakon – Drugs
Vigilare – to watch or to see
Pharmacovigilance is the science and activities relating to the
detection, assessment, understanding and prevention of adverse
effects or any other medicine/vaccine related problem.

Origin of Pharmacovigilance
Special issues in pharmacovigilance:
Drug Name Year Removed Reason removed
Diethlylstilbestrol (DES) 1971 Vaginal tumours in girls and young
women
Phenformin 1978 Lactic acidosis
Phenolphthalein 1997 Carcinogenicity
Troglitazone 2000 Hepatotoxicity
Rofecoxib 2004 Risk of Myocardial Infarction
Rosiglitazone 2010 Increase risk of heart attack and deaths

WHO INTERNATIONAL
DRUG MONITORING
PROGRAMME

WHO INTERNATIONAL DRUG
MONITORING PROGRAMME
Under the auspices of 10 countries, a 3 year feasibility
study of a collaborative international program of
pharmacovigilance was begun by Professor Jan Venulet in
1968 funded by USA.
Professor Venulet and the FDA’s Drug safety group
developed a thesaurus DART, to describe spontaneous
report in uniform body system based terminology.

Later in FDA, DART evolved into COSTART (Coding
symbols for thesaurus of adverse reaction terms).
COSTART used until MedDRA (Medical terminology for
drug regulatory authorities) was adopted in later 1990s by
the European commission as a part of ICH.

Venulet developed a program agreed to by members states for
recording, storing, and retrieving incoming spontaneous reports into a
database, as well as methodologies for analysing the data received.
This is known as International Drug Monitoring Programme which
then moved to WHO headquarters in Geneva, Switzerland.
In 1978, the program was moved to Uppsala, Sweden.

Uppsala Monitoring centre’s mission is to Safeguard patients and to:
Lead the research and development tools and methodologies for
pharmacovigilance and patient safety
Lead and support global pharmacovigilance activities
Develop effective networks and sustainable pharmacovigilance system
Apply best practices in communication and networking with stakeholders
Provide high quality and cost effective tools, services and international
dictionaries, classification and terminologies for pharmacovigilance and
patient safety
Build an effective organization for the future

This monitoring program now serves over 80 countries
with annual meeting exchange practices, provide training,
and serve as a database of adverse events from member
countries.

FUNCTIONS OF WHO INTERNATIONAL
DRUG MONITORING PROGRAMME
Identification and analysis of new adverse reaction signals from the
case report information submitted to the national centers.
Information exchange between WHO and national centers through
“Vigimed”
Publication of periodical newsletters
Supply of tools for management of clinical information (WHO drug
dictionary and the WHO adverse reaction terminology).

Training and consulting support to national centers and
countries establishing pharmacovigilance system
Computer software for case report management
Annual meeting for representatives of national centers

Methodological research for the development of
pharmacovigilance
Publication of various scientific articles in
pharmacovigilance.

PHARMACOVIGILANCE
PROGRAM OF INDIA (PVPI)

PHARMACOVIGILANCE PROGRAM OF INDIA
(PvPI)
In 1986 – Proposed ADR monitoring system for India (12
Regional Centres)
In 1997 – India joined WHO-ADR monitoring programme (3
centres i.e. AIIMS, KEM and AMU)
In 2004 – National pharmacovigilance program (2 zonal, 5
Regional, 24 Peripheral Centres)
In 2010 – Pharmacovigilance programme of India (PvPI)

NATIONAL PHARMACOVIGILANCE PROGRAM ZONES IN INDIA
CDSCO
N N N E E E S S S S W W W W
E S
National PV Centre
Zonal PV Centre
Regional PV Centre
Peripheral PV Centre

(PvPI)
 PvPI was initiated by CDSCO, New Delhi in July 2010 with AIIMS
New Delhi being the National Coordinating Centre (NCC) for
monitoring ADRs.
Then later the National coordinating centre was shifted to the Indian
Pharmacopoeia Commission (IPC), Ghaziabad, (U.P.) in 15th April,
2011.

(PvPI)
Mission:
Safeguard the health of the Indian population by ensuring that the
benefits of use of medicine outweighs the risks associated with its
use.

(PvPI)
• Develop and implement pharmacovigilance system in India
• Encourage health care professionals in reporting of adverse
reaction to drugs, vaccines, medical devices
• Collection of adverse reactions reports
Short
term goals
• Expand the PvPI to all hospitals across India.
• To develop and implement e-reporting system.
• To make ADR reporting mandatory for health care
professionals.
Long term
goals

(PvPI)
Objectives:
To create a nation-wide system for patient safety reporting.
To identify and analyse new signals from the reported cases.
To analyse the benefit-risk ratio of marketed drug products.
To generate evidence based information on drug safety.
To promote rational use of medicines.

COMMUNICATIONS UNDER PvPI
Health Care Professionals
ADR Monitoring Centres
NCC, IPC, Ghaziabad
Uppsala Monitoring Centre, Sweden
CDSCO, Headquarter, New Delhi
CDSCO Zonal Offices – 4 Zone

(PvPI)
This program is monitored by different committees under NCC:
 Steering Committee
 Strategic Advisory Committee
Technical support will be provided by:
 Signal Review Panel
 Core Training Panel
 Quality Review Panel

(PvPI)
ADR Will be collected from:
Medical council of India (MCI) approved medical colleges and
hospitals
Private hospitals
Public health programs
Autonomous institutions (ICMR)

GOVERNANCE OF PvPI
Steering
Committee
Strategic Advisory
Committee
Signal
Review
Panel
Core
Training
Panel
Quality
Review
Panel
PvPI – Headquarters
Central Drugs Standards Control Organisation
Ministry of Health and Family Welfare (MoHFW)
Government of India
National Pharmacovigilance Coordinating Centre
Indian Pharmacopoeia Commission
Ghaziabad, UP
CDSCO Zonal and
Subzonal Centres
North
South
East
West
ADR Monitoring Centres

(PvPI)
 The PvPI Programme had been planned to be implemented in 3 phases:
1. Phase I: To set up 40 ADR Monitoring centres (AMC) would be rolled out
in 2010.
2. Phase II: To set up 140 MCI recognized medical colleges by 2011.
3. Phase III: Programme would ultimately cover the healthcare system by
2013.
 AMCs operates with logistic support from their respective Zonal CDSCO
centres situated at Ghaziabad, Kolkata, Mumbai and Chennai.
CDSCO Headquarters at New Delhi controls the Zonal Centres.

Year Events
1848 Girl child death due to chloroform anaesthesia
1901 Contaminated Diphtheria antitoxin toxicity
1937 Sulfanilamide elixir toxicity
1961 Thalidomide Tragedy
1968 WHO international Drug Monitoring Programme
1986 India Proposed ADR Monitoring System
1997 India Joined WHO ADR Monitoring Programme
2004 National Pharmacovigilance Programme launched in India
2010 Pharmacovigilance programme of India Initiated
DEVELOPMENT OF PHARMACOVIGILANCE IN INDIA

REFERENCE
1. Elizabeth B. Andrews, Nicholas Moore. Mann’s
Pharmacovigilance. 3rd Edition. Wiley Blackwell. 2014.
2. Borton Cobert. Cobert’s Manual of Drug Safety and
Pharmacovigilance. 2nd Edition. Jones and Bartlett Learning. 2012.
3. S. K. Gupta. Textbook of Pharmacovigilance. 2nd Edition. Jaypee
Brothers Medical Publishers. 2019.

History of Pharmacovigilance

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