This presentation will give a view on the history that led to the present level of stringent monitoring of adverse drug reaction.

1. History that lead to
Pharmacovigilance
Lecture by
Siraj Sundaran
1

2. Pharmacovigilance
• Greek work “Pharmakon” mean drug related and Latin word
“Vigilia” means to watch.
• Definition: The science and activities relating to the detection,
assessment, understanding and prevention of adverse effects
or any other medicine/vaccine/biologicals/medical devices
related problem thereby reducing the risks and increasing the
benefits of the medicine.
2

3. • All medicines and vaccines undergo rigorous testing for safety
and efficacy through clinical trials before they are authorized
for use.
• However, the clinical trial process involves studying these
products in a relatively small number of selected individuals
for a short period of time.
• Certain side effects may only emerge once these products
have been used by a heterogenous population, including
people with other concurrent diseases, and over a long period
of time.

4. Pharmacovigilance need for a drug
• Quantification of risk/s.
• New ADRs or Signals.
• Special population risks.
• Long term use risks.
• Comorbidity related risks.
• Drug interaction risks.
• Improves patient care and safety in relation to the use of medicines.
• Assess the benefit and risk of the drugs.
• Can aid in safe, effective (therapy and cost) and rational drug use.
• Communication to the health care and public.
4

5. Few historical records
• Adverse reactions has a history that goes beyond 150 years
before.
• 1848- A 15 year old girl (Hannah Greener) was given
chloroform as general anesthesia for removing ingrown nail in
the toe. Had fibrillation of ventricles and resulted in death.
5

6. 6

7. • 1863- Lancet initiated the collection of notification of side-
effects.
• 1902- Biological Control Act by USA as a result of death due to
contaminated diphtheria vaccine. Then the vaccines were
produced from horses. And a horse called Jim contracted
tetanus thereby death of many children.
7

8. • 1905- Samuel Hopkins Adams published “The Great American
Fraud” which exposed many of the false claims by the
patents.
• 1906- USFDA required drug clean and free of contaminations.
• 1936 to 1937- more than 100 cases of sulphanilamide lethal
cases (cause was use of diethylene glycol as solubiliser). Elixir
which gave Ad of taste of raspberries was called as taste of
death. The Federal Food, Drug and Cosmetic act was
formulated in 1938.
8

9. • 1938- USFDA gave requirement purity and free of
contamination of drugs.
• 1938- Also saw major issues of acetyl salicylic acid use related
melena as a major concern which was published. Although it
was not proved then it was confirmed in the year 1955.
• 1952- Choramphenicol induced hematotoxicity was reported.
9

10. • 1957 to 1961- Thalidomide was marketed in 46 countries.
Wide use: Sedative hypnotic, antiemetic, anticancer, skin lesions,
etc., and the most safe dose.
About 10,000 children were born with devastating
malformations in various countries worldwide.
1961 two clinicians Lenz and Mcbride, confirmed thalidomide
used for morning sickness to be the cause of this crisis.
Besides fetal disabilities there were also a lot of large number of
abortions reported in women.
1961 November- Thalidomide was withdrawn from most of the
countries.
10

11. 11

12. • 1962- US Kefauver Harris amendment to the law for safety
and efficacy of drug.
• 1964- UK introduced the “Yellow card” system.
• 1965- European legislation made their attempt for protection
of public health.
• 1968- WHO started the programme of International Drug
Monitoring. Ten members participated in this: Australia, UK,
USA, Canada, Germany, Ireland, Sweden, Denmark, New
Zealand, Netherlands (Italy joined in this venture on 1975).
12

13. • 1978- Uppsala monitoring centre was established by the WHO
for the International Drug Monitoring.
• 1982- Benoxaprofen disaster: 61 deaths and nearly 3500 side
effects.
13

14. • 2006- Elephant man drug trial, 6 healthy men as a part of trial
were given with a novel monoclonal antibody. The drug was
intended for auto immune disease and leukaemia. The drug
was given IV and in sub- clinical dose.
Within a span of 60 minutes the subjects showed multiple
adverse reactions which were severe and life threatening.
This was also leading to the multiple organ failures. Within 16
hours they had go be put in intensive care and about 3 weeks
treatment.
14