Unit -1
Introduction to Pharmacovigilance
1.1 Pharmacovigilance
relating to the detection, assessment, understanding and prevention of adverse effects or any other
medicine-related problem.
Objectives of Pharmacovigilance
Pharmacovigilance covers the entire life-cycle of a medicinal product. Underlying objectives of
pharmacovigilance are:
Preventing harm from adverse reactions in humans arising from the use of authorized
medicinal products within or outside the terms of marketing authorization or from
occupational exposure
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.
1.2 History of Pharmacovigilance:
Over the years, there have been numerous events that have led to the creation of modern
pharmacovigilance.
1848 Chloroform
The history of pharmacovigilance years back to 1848, when a series of suspicious deaths
occurred in Great Britain during operations in which chloroform was used to patients as an
anesthetic and it was used as an anesthetist starting in 1847 and a 15-year-old girl died with
the use of Chloroform. This tragic event generated concern, warning the Lancet Journal to
set up a commission and urge British doctors to report similar cases. Therefore, A debate
was opened on the safety of anesthetic procedures and with the presentation of various
reports, the drug ceased to be used as an anesthetic in 1876. This was the first step towards
the establishment of pharmacological safety procedures.
1937 Sulfanilamide
Another turning point occurred in the relevance of Drug Safety in United States in 1937,
when 107 people, including 76 newborns, lost their lives due to a Sulfanilamide liquid
formulation of containing the solvent Diethylglycol as a diluent. Currently, this component
is known for its high toxicity and is used as an antifreeze liquid in car engines. This tragedy
highlighted the importance of ensuring the safety not only of the active ingredient, but also
of the excipients that make up the drug.
1961 Thalidomide
In 1961, there was possible correlation was reported between fetal abnormalities and
Thalidomide. In 1961, Doctor William Griffith McBride reports the first cases of fetal
abnormalities linked to Thalidomide. The use of Thalidomide during pregnancy caused a
20% increase in congenital malformations in newborns. The drug was tested for two years
on 300 patients, without detecting any particular side effects. Therefore, considered safe,
it was marketed in over 50 countries starting from 1957.
Thalidomide was used predominantly as a sedative, antiemetic and hypnotic in pregnant
women. Its administration affected a serious anomaly in the development of the fetus with
serious deformities of the limbs, especially the upper ones, such as the absence (amelia) or
reduction of the bones (phocomelia). Approximately 10,000 to 20, 0000 children suffered
incomplete development.
1.3 History of pharmacovigilance: Birth of the bodies
Following these events, the first bodies and procedures emerged aimed at monitoring the
safety of the drug.
In 1938, the Food, Drug and Cosmetic Act (FFDCA, FDCA, or FD&C) was established
in the United States, a set of laws to charge the Food and Drug Administration (FDA)
(established in 1906) with supervising the safety of foods, drugs, medical devices and
cosmetics, laying the foundations of pharmaceutical legislation.
In 1948, the World Health Organization (WHO) was founded in Geneva to centralize
health issues worldwide.
In 1962, following the Thalidomide accident, the Harris-Kefauver amendments were
introduced in the United States, which instructed the need to conduct mandatory preclinical
studies. Only after the evaluation of the results of these studies it was possible to start the
clinical trial phase on humans. Moreover, the marketing authorization depended on the data
obtained in the three phases of the clinical trial. After marketing, the drugs were subjected
to post-marketing surveillance.
In the United Kingdom, the Yellow Card, the first form for reporting adverse reactions by
doctors, was introduced in 1964.
In 1968, WHO promoted the Program on International Drug Monitoring (PIDM), an
international drug monitoring program aimed at centralizing global data on adverse
reactions. 10 states were initially involved in this program; Australia, Canada,
Czechoslovakia, Ireland, the Netherlands, Germany, New Zealand, Sweden, the United
Kingdom, the USA and Italy joined in 1975.
The program was immediately effective: the following year it emerged that Clioquinol, an
anitimycotic drug, caused retrobulbar optic neuritis in Asian countries, revealing an ethnic
susceptibility to the drugs and their adverse effects.
Likewise, in 1971 it emerged that diethylstilbestrol, an estrogen of synthetic origin, which
had been used since the 1940s to pregnant women to prevent spontaneous abortions and to
relieve nausea, caused genital tumors in the daughters of women exposed to this substance
during pregnancy. In that same year, WHO created the global reporting database located
in Uppsala, Sweden.
In 1973, France inaugurated the first six hospital surveillance centers, where the term
pharmacovigilance was formally adopted.
In 1978, The Swedish government and the WHO founded the Uppsala monitoring center.
In 1995, the European Medicines Agency (EMA) was founded.
In 2001, Eudravigilance, the European database for the management of reports, was
implemented.
In 2001, the National Pharmacovigilance Network (RNF) was created in Italy to collect
reports of adverse reactions at a national level.
In 2003, the Italian Medicines Agency (AIFA) was created. As proof of the growing
awareness at a national level, some collaborative groups were established such as the
Interregional Pharmacovigilance Group (GIF) and the Italian Group for Epidemiological
Studies in Dermatology (GISED).
Furthermore, since 2006, Italian healthcare companies have been obliged to designate a
qualified person as responsible for pharmacovigilance activities (QPPV).
In 2012, the Pharmacovigilance Risk Assessment Committee (PRAC) was established
The European pharmacovigilance system was further strengthened, clearly defining roles
and responsibilities. The PRAC is responsible for evaluating and monitoring the safety of
medicines for human use, providing recommendations to the relevant committees.