The slides in this presentation mainly focus on History and Progress of Pharmacovigilance, significance of safety monitoring and Pharmacovigilance in India & International aspects.

1. MAULANAAZAD EDUCATIONAL TRUST’S
Y. B. CHAVAN COLLEGE OF PHARMACY,
AURANGABAD.
BASIC ASPECTS OF PHARMACOVIGILANCE
Prepared by
 Andhale Sujeet Babasaheb
 Roll No – 46
 M. Pharm Sem II
 Subject Incharge– Dr. Khan Dureshahwar
Department of Pharmacology 1

2. Basic Aspects Of Pharmacovigilance
 History And Progress of Pharmacovigilance
I. Choloform (1848)
II. Sulfanilamide Elixir (1937)
III. Thalidomide Tragedy
 Significance of Safety Monitoring
 Pharmacovigilance in India and International Aspect
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3. History of Pharmacovigilance
I. Choloform
 The history of Pharmacovigilance started 169 years ago, on Jan 29, 1848, when a young
girl (Hannah Greener) from the north of England died after receiving chloroform
anesthetic before removal of an infected toenail.
 Sir James Simpson had discovered that chloroform was a safer and powerful anesthetic, and
he had introduced it in clinical practice.
 The causes of Hannah's death was investigated to understand what happened to Hannah, but
it was impossible to identify what killed her. Probably she died of a lethal arrhythmia or
pulmonary aspiration.
 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
II. Sulfanilamide Elixir
 In 1937, there were 107 deaths in the USA, because of the use of sulfanilamide elixir,
containing diethyl glycol as the solvent. This solvent was considered the cause of deaths,
but the manufactory companies were not aware about its toxicity at that time.
 Consequently, the Federal Food, Drug and Cosmetic Act was established in 1938; its
aim was to renovate the public health system. 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
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4. III. 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.
 Dr. McBride, an Australian doctor suggested a connection between congenital
malformation of babies and thalidomide. In fact, he observed that the incidence of
congenital malformations of babies (1.5%) had increased up to 20% in women who
had taken thalidomide during pregnancy. Also in Germany Dr. Lenz suggested a
correlation between malformations and thalidomide and his suspect was published in a
German Journal.
 POST THALIDOMIDE EVOLUTION:
Necessity to monitor drug products for efficacy and safety increases.
Regulatory changes following thalidomide tragedy:
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5.  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).
 In 1968, the WHO Programme for International Drug Monitoring was
instituted and ten members participated in this program (Australia, UK,
USA, Germany, Canada, Ireland, Sweden, Denmark, New Zealand, and
Netherlands). Italy participated in this program in 1975.
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6. Year Dvelopment
1747 Very first known clinical trials by James Lind, proving the usefulness of
lemon juice in preventing scurvy.
1937 Death of more than 100 children due to toxicity of sulfanilamide.
1950 Apalstic anemia reported due to chloramphenicol toxicity.
1961 Worldwide tragedy due to thalidomide toxicity.
1963-1968 WHO research project for international drug monitoring on pilot scale.
1996 Global standards level clinical trials initiated in India.
1997 India attached with WHO Adverse Drug Reaction Monitoring Program.
1998 Initiation of pharmacovigilance in India.
2002 67th National Pharmacovigilance Center established in India.
2004-2005 India launched National Pharmacovigilance Program.
2005 Accomplishment of structured clinical trials in India.
2009-2010 Pharmacovigilance Program (PvPI) started.
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Table 1: The sequential pharmacovigilance developments with special reference to India:
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7.  Drug safety monitoring is the process of identifying expected and unexpected
adverse reactions resulting from the use of medicines in the post-marketing phase.
It is a risk mitigation exercise in which the ADRs caused by therapeutic drugs,
biologicals or devices can explored, prevented or minimized.
 Before releasing into the market, a medicine is tested using a limited population
ranging from 500 to 5000. (Phase-I to Phase-III)
 Once the medicine comes into the market it becomes legally available for
consumption by the general population.
 The population may be children, pregnant women, patients suffering from other
diseases and the elderly.
 It may be given separately or in combination with other medicines.
 Thus, the drug is taken in different therapeutic situations and physiological
conditions.
 It is therefore, very much necessary to observe and record the effectiveness and
safety of the medicine under real-life conditions. A close and effective monitoring
is required to assess the risks associated with the use of medicines. In fact adverse
effects, interactions with foods or with other medicines and risk factors are to be
noticed only during its real use over the years. 7
 Significance of Safety Monitoring
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8.  Thus, a close and effective monitoring is required to assess the risks associated
with the use of medicines.
 This is possible only when all the stake holders extend their hands in the field
of pharmacovigilance to make such collaboration successful. effective and
comprehensive systems are required. The typical limitations include lack of
training, resources, political support, and scientific infrastructure. For
future development of the science and practice of pharmacovigilance,
understanding and knowledge of tackling are essential.
 In general, the stakeholders who need to collaboratively work are:-
 1. Government 2. Industry 3. Hospitals and academia.
 4. Medical and pharmaceutical associations
 5. Poisons and medicines information centres.6. Health professionals
 7. Patients 8. Consumers 9. The media 10. World Health Organization(WHO)
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9.  International Aspect Of Pharmacovigilance
 PRESENT SCENARIO PHARMACOVIGILANCE
Oversea OF The position of the pharmacist within the health care system has
continually been subject to discussion and change. The pharmacist‟s primary mission
traditionally has been to dispense drugs as prescribed by a physician and to ensure
that these drugs meet the required standards. Nowadays the pharmacist also
frequently acts as a consultant on pharmacotherapy.
In the United Kingdom and United States, pharmacists are, to a degree, also
authorized to write out prescriptions, which incidentally has been a long-standing
practice in many countries where doctors are in short supply. Whereas initially the
pharmacist‟s role focused on the chemical aspects and raw materials of drugs, the
local production of medicines, and the dispensing role, today it has shifted more
toward reducing the prevalence of ADRs and drug-drug
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 Pharmacovigilance in India and International Aspect
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10.  Interactions, and providing information and instruction about appropriate drug
use. The pharmacist has become a consultant on drug therapy, both for physicians
and patients.
 In the Netherland a legislative bill is being prepared to award the pharmacist the
official status of co-consultant, thus making him jointly responsible for
pharmacotherapy. The role pharmacists play or are given to play also depends on the
circumstances in which they exercise their profession. Nevertheless, the fundamental
role of the pharmacist will always be to ensure that medicines are used safely.
 The literature mentions several other ways pharmacists can contribute to the safe use
of drugs. In addition to their responsibilities relating to drug dispensing and
compliance, pharmacists can play a prominent role in areas such as record keeping,
education, and monitoring over the counter products and alternative therapies and
because computerized dispensing drug systems are becoming more prevalent, the
pharmacist‟s role is becoming more important, both as a user and in his/her capacity of
system manager. The reporting of ADRs is one of the roles pharmacists could have to
play with seriously.
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11. Indian Aspect Of Pharmacovigilance
 Pharmacovigilance in India India has more than half a million qualified Doctors
and 15, 000 hospitals having bed strength of 6, 24,000. It is the fourth largest
producer of pharmaceuticals in the world.
 It is emerging as an important Clinical trial hub in the world. Many new drugs are
being introduced in our country. Therefore, there is a need for a vibrant
pharmacovigilance system in the country to protect the population from the
potential harm that may be caused by some of these new drugs.
 Clearly aware of the enormity of task the Central Drugs Standard Control
Organization (CDSCO) has initiated a well structured and highly participative
National Pharmacovigilance Program.
 It is largely based on the recommendations made in the WHO document titled
“Safety Monitoring of Medicinal Products – Guidelines for Setting up and
Pharmacovigilance Centre”. Running a The National Pharmacovigilance
Program was officially inaugurated by the Honorable Health Minister Dr.
Anbumani Ramadoss on 23November, 2004 at New Delhi.
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12.  The specific aims the Pharmacovigilance Programmers are to of
 1. Contribute to the regulatory assessment of benefit, harm, effectiveness and risk
of medicines, encouraging their safe, rational and more effective (including cost
effective) use.
 2. Improve patient care and safety in relation to use of medicines and all medical
and paramedical interventions.
 3. Improve public health and safety in relation to use of medicines.
 4. Promote understanding, education and clinical training in pharmacovigilance and
its effective communication to the public.
Causes of failure of implementation of pharmacovigilance in India
However, what needs to be more important along with the funding is a focused vision
and effective strategy for developing the pharmacovigilance systems, especially in the
DCGI Office, which is lacking.Traditionally, pharmacovigilance was never done in
India in Pharmaceutical companies, be it Indian or MNCs, so there is an immense
shortage of knowledgeable people who will be able to advice the DCGI on this matter,
as pharmacovigilance is a very complex subject, intertwined regulations and complex
systems.
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13. CURRENT PROBLEMS PHARMACOVIGILANCE
1. Topical tacrolimus (Protopic) and pimecrolimus (Elidel): potential cancer
risk.
2. Duloxetine (Yentreve, Cymbalta): need for monitoring.
3. Tenofovir (Viread): interactions and renal adverse effects.
4. Linezolid (Zyvox): severe optic neuropathy.
5. CosmoFer and high risk of anaphylactoid reactions.
6. Drotrecoginalfa (activated) (Xigris): risk benefit in the management of
sepsis.
7. Rosuvastatin (Crestor): introduction of 5 mg starting dose.
8. Osteonecrosis of the jaw with bisphosphonates.
9. High dose inhaled steroids: new advice on supply of steroid treatment
cards.
10. Local reactions associated with preschool d/D Tap-IPV boosters.
11. Salmeterol (Serevent) and formoterol (Oxis, Foradil) in asthma
management.
12. Risk of QT interval prolongation with methadone.
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14. Future aspect of pharmacovigilance in India
 With more and more clinical trials and other clinical research activities being
conducted in India, there is an immense need to understand the importance of
pharmacovigilance and how it impacts the lifecycle of the product.
 Given this situation at present, the DCGI should act quickly to improve
pharmacovigilance so as to integrate Good Pharmacovigilance Practice into the
processes and procedures to help ensure regulatory compliance and enhance
clinical trial safety and post marketing surveillance.
 A properly working pharmacovigilance system is essential if medicines are to be
used safely. It will benefit all parties including healthcare professionals and
regulatory authorities.
 Scope
 For those looking to pursue a career in pharmacovigilance, there are several job
opportunities available in India. These include positions at pharmaceutical
companies, hospitals, medical research institutes as well as government regulatory
bodies like the Central Drugs Standard Control Organization (CDSCO)
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15. Pharmaceutical consumers.
It companies helps and the pharmaceutical companies to monitor their medicines
for risk and to devise and implement effective risk management plans to save their
drugs in difficult circumstances. Having considered the problems and challenges
facing the development of a robust pharmacovigilance system for India, the
following proposals might be follows:
1.Building and maintaining a robust pharmacovigilance system.
2. Making pharmacovigilance reporting mandatory and introducing
pharmacovigilance inspections.
3. High-level discussions with various stake holders.
4. Strengthen the DCGI office with trained scientific and medical assessors for
pharmacovigilance.
5. Creating a single country-specific adverse event reporting form to be used by
all.
6. Creating a clinical trial and post marketing database for SAEs / SUSARs and
ADRs for signal detection and access to all relevant data from various
stakeholders.
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16. 7. List all new drugs / indications by maintaining a standard database for every
pharmaceutical company.
8.Education and training of medical students, pharmacists and nurses in the area of
pharmacovigilance.
9. Collaborating with pharmacovigilance organizations in enhancing drug safety
with advancements in information technology, there has been the emergence of
new opportunities for national and international collaborations that can enhance
postmarking surveillance programs and increase drug safety. The Uppsala
Monitoring Center (UMC) is an example for an international collaboration to
establish a harmonized post marketing surveillance database.
10.Building a network of pharmacovigilance and pharmacoepidemiologists in
India.
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17.  Refrences
1. Elizabeth B. Andrews, Nicholas Moore. Pharmacovigilance. 3rd Edition. Wiley
Blackwell. 2014. Mann’s
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.
4. A Book of Pharmacovigilance By Dr. D.K.Tripathi, Dr. Shiv Shanhar Shukla Dr,
Ravindra Pandey Nirali Prakashan,First edition, August 2019, Page no:-1.7 to 1.8.
5. Ghewari, Priyanka & Salunkhe, Sachin & Bhatia, Neela & Killedar, Suresh.
(2014). Strategies and current scenario of pharmacovigilance in India. Journal of
Advanced Drug Delivery. 1. 122-134.
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18. Thank-you !
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