Introduction to Pharmacovigilance  History and development of Pharmacovigilance  Importance of safety monitoring of Medicine  WHO international drug monitoring programme  Pharmacovigilance Program of India(PvPI)

1. PHARMACOVIGILANCE
MISS. GAYATRI K. BAHATKAR
ASSISTANT PROFESSOR
P. R. PATIL INSTITUTE OF PHARMACY, TALEGAON SP.

2. Definition of pharmacovigilance
• According to WHO, pharmacovigilance is the science of collecting, monitoring,
researching assessing and evaluating information from healthcare provider and
patient of the adverse effect of medication.
• Prior identification of adverse drug reactions is most important for safety of a
patient taking medicine.
• The information received from health care providers, pharmaceutical
companies and patients should be evaluated in order to assess the risk and
benefits involved with respect to a particular drug.
• A careful monitoring of drug usage at every step such as pharmacovigilance
inspection, reporting of ADR, periodic collection of safety report, post-
authorization safety studies is required.

3. Aim of
pharmacovigilance
• Patient safety- improve patients safely with
Ips
• IP efficacy- see if IP is effective
• SAEs- track serious adverse events
• Population- improve public health
• Risk benefit- review risk, benefit, efficacy
for rationalized use of IP
• Educate- educate on IP safely.

4. The important purpose of pharmacovigilance programmes are
• To improve patient care
• To provide medicines and all medical and paramedical services safe .
• To improve public health services
• To assess benefit, risk, and effectiveness of medicines
• To encourage safe, rational, therapeutically effective and cost-effective use
of medicines
• To promote understanding, educating and clinical training in
pharmacovigilance, and
• To support effective communication to health care professionals and the
public.

5. Pharmacovigilance
Benefit risk
assessment of
drugs
Patient safety
Education and
training
Public health
Rational use of
drug
WHO /Uppsala
monitoring
center
Pharmaceutical
companies
Hospitals /
academic
Healthcare
worker
Patients
Nationals /
regionals pv
centres
Acting to protect public health

6. History and development of pharmacovigilance
• In more recent times, serious adverse reactions associated with medical
products resulted in the evolution of regulatory changes and an effort to
discover drug safety issues as early as possible.
• Pharmacovigilance is the practice used by sponsors and regulatory
bodies to detect harmful effects associated with medical products to
identify potential risks and enable warnings to reach physicians in a
timely manner.
• 1847- chloroform- James young simpson- chloroform induced syncope
• 1893- lancet setup commission for death due to anaesthesia
• 1897- diacetylmorphine – felix hoffmen- Bayer lab
• 1937- Domagk – prontosil red- sulphonamide derivative-
sulphonilamide

7. • 1938- federal food drug and cosmetic act was passed
under which pharmaceutical product manufacturers would have to show scientific
evidences Many children in the 1960’s
• 1954- stalinon diioddiethyl – neurotoxicity
• 1959- visa legislation
• 1961- thalidomide disaster- chemie gruenthal company.
• McBride began to associate this so-called harmless compound with severe birth
defects in the babies he delivered. The drug interfered with the babies’ normal
development, causing many of them to be born with phocomelia, resulting in
shortened, absent, or flipper-like limbs. A German newspaper soon reported 161
babies were adversely affected by thalidomide, leading the makers of the drug- who
had ignored reports of the birth defects associated with the it to finally stop
distribution within Germany. Other countries. Followed suit and, by March of 1962,
the drug was banned in most countries where it was previously sold.

9. • 1962- kafouvers- harris amendment act
• legislators tightened restrictions surrounding the surveillance and approval
process for drugs to be sold in the U.S., requiring that manufacturers prove
they are both safe and
• 1963- resolution WHA 16;36
• 1964- UK started yellow card system
• 1965- European union issue EC directive 65/65
• 1968- WHO started pilot project for the purpose of pool ADR
• 1970-Diehtyl stillbestrol drug- induced viginal carcinoma(1.6 lakh cases)
• 1989- antiarrhythmic drug used in CAST study- PVC killer ( premature
ventricular contraction )

10. • 1997- ICH E2 adopted electronic reporting
• 1999- revised medwatch ,draft medDRA by USFDA released
• 2001- post marketing safety reporting guideline issue
• 2002- PDUFA lll ( prescription drug user fee act)
• 2005- final risk management guideline issued
• 2007- FDA amendment act.
• 2010- new IND reporting and European pv legislation
• 2012 –European pv legislation effective
• 2014-MHRA good Pv practice for medicine

11. Importance of safety monitoring of medicine
• The clinical development process of medicine .Till a medicine not approved for sale its
remains protected under scientific environment of clinical trials. Before release for sale , a
medicine is tested using a limited population ranging from 500 to 5000, once the medicine
into the market.
• Once the medicine comes into the market, it becomes legally available for consumption
by the general population. The population may be children's , pregnant women ,patients
suffering from other diseases and the elderly.
• It may be given separately or in combination with other medicine
• It is therefore very much necessary to observe and record the effectiveness and safety of
the medicine under real life condition ,
• In fact adverse effect interaction with food or with other medicine and risk factor are to
be noticed only during its real use over the year.

12. Pre-clinical animal
experiments
Animal experiments for
acute toxicity , organ
damage , dose
dependence,
metabolism, kinetics,
carcinogenicity,
mutagenicity/
teratogenicity
Clinical studies
Phase l
20-50 healthy
volunteers to
collect
preliminary data
Phase ll
150- 350 subjects with
diseases- to
determine safety and
dosage
recommendation
Phase lll
250-4000 more varied
patient groups- to
determine short-term
safety and efficacy
Phase- lV
Post- approval
studies to determine
specific safety issues
Spontaneous
reporting

13. Year Drug Adverse reactions Remarks
1950 Chloramphenicol Aplastic anaemia Still being used
1961 Thalidomide Phocomelia National disaster
1970 Clioquinol Smon After 30 years of use
1970 Diethylstillbesterol Adenocarcinoma In utero expouser
1975 Practolol Oculo-mucocutaneous syndrome 5 years after marketing
1976 Zomepirac Anaphylaxis Withdrawn
1978 Phenformin Lactic acidosis Withdrawn

14. Year Drug Adverse reaction Remarks
1978 Phenformin Lactic acidosis Withdrawn
1980 Ticrynafen Death from liver disease Detected after 5 years of
suspection
1982 Ticrynafen Hepatitis Withdrawn
1990 Etretinate Birth defect high risk of birth defect narrow
therapeutic index
1999 Astimizole Arrhythmias Because of interaction with other
drugs
2004 Rofecoxib Myocardial infraction Withdrawn
2007 Inhaled insulin Long term safety ,high cost Withdrawn in UK due to poor sales
caused by national restriction on
prescribing , doubts over long term
safety.

15. • Thus closed and effective monitoring is required to asses the risk associated
with the use of medicine. This is possible when all the stakeholder extend
their hand in the field of PV to meet the challenges . To make such
collaboration saucerful the effective and comprehensive system are
required. The typical limitation include lack of training, recourses ,political
support and scientific infrastructure for the future development of the
science and practice of pv .

16. 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 centers
• 6. Health professionals
• 7. Patients
• 8. Consumers
• 9.The media
• 10. World Health Organization

17. WHO international drug monitoring programme
• During the 16th World Assembly in 1968, the 16.36 resolution was called for "a systematic
collection of information on serious adverse drug reactions during the development and
particularly after medicines have been made available for public use". This finally
appeared as the WHO Programme for International Drug Monitoring (PIDM).
• The WHO encourages pharmacovigilance at country level. Initially, the WHO PIDM was
formed with members of 10 countries. Till May 2016, 124 countries have joined the WHO
PIDM and 29 associate members are waiting for full membership.
• Reports on adverse reactions associated with medicinal products are to be submitted by
WHO PIDM Member States. This is known as Individual Case Safety Reports (ICSRs) and it
is recorded as the WHO global database. The WHO Programme for International Drug
Monitoring offers a forum for WHO member states to work together in
pharmacovigilance,VigiBase™.

18. • VigiBase is managed and maintained by the WHO Collaborating Centre for
International Drug Monitoring, known as the Uppsala Monitoring Centre. There
were over 10 million reports of adverse drug reactions in VigiBase till October
2014. Data in VigiBase are recorded in a structured and comprehensive manner
to allow the detection of potential medicinal safety hazards.
The objectives of pharmacovigilance are:
• To improve patient care and patient safety with respect to the use of medicines;
and
• To support public health programmes by supplying reliable, balanced
information to assess the risk-benefit profile of medicines.
• History – established in 1968 with 10 country
• IDMC –WHO Geneva- who collaborating center of international drug monitoring
– Upssala

19. • UMC- non profit organization =WHO + Swedish govt.
• Vision and goal of UMC
• In science and concept of pharmacovigilance
• Prevent harm to human from medicine
• Gather and share objective intelligence and opinion for drug safety by transparent
communication
• Support and promote of rational used of medicine so improved patient therapy And
public health.
• Global education and communication in benefit, harm, effectiveness and risk of medicine
Activity of UMC
• Developing leading edge system and science to identify and communication of safety
hazard from drugs

20. • Carryout research within ethical , intellectual and scientific boundary of theory
and practice of PV
• Pursuing active collaboration and communication with all sketch holders
• Pursuing goal of single global database for drug safety
• Ensure to never miss signal of potential hazards
• All stakeholder ensure to evaluate and learn for decision
• Encourage growth of PV
• Promote existing centres and stakeholders
• Share info openly and transparently
• Stimulate harmonized sys worldwide for Pv
• Maintain and develop useful products and tools and services in pursuit = vision
and goal programme

21. Communication about safety of medicines
Methods of communication Issued by
Letters to the Doctors Pharmaceutical Manufacturer
Medicine alerts National health authorities
Media statements National health authorities/Pharmacovigilance
centres
Leaflets for informationTo the
patients
Pharmaceutical Manufacturer/National
HealthAuthorities/Pharmacovigilance centres
News letters National Pharmacovigilance centres andWHO
Personal feedback to Reporters National Pharmacovigilance centres

22. The collaborating center is responsible for maintaining the global ADR database,
VigiBase. At present the database contains more than three million ADR reports.
The WHO Collaborating Centre analyses the reports in the database to:
• Identify early warning signals of serious adverse reactions to medicines;
• Evaluate the hazard;
• Undertake research into the mechanisms of action to support the development of
safer and more effective medicines.
Through an advisory committee, the WHO plays an important role in the provision of
expert advice on all matters relating to the safety of medicines. The Committee also
assists consistently for implementation of the policies and actions among the
member countries and advises those who are concerned about the action taken in
another country.

23. Pharmacovigilance in India
• The concept of pharmacovigilance is not new to India. It is in its earlier stage. In about
1986 a formal ADR monitoring system consisting of 12 regional centers was proposed for
India. Each center would cover a population of 50 million.
• In the year 1989, six regional centers in Mumbai, New Delhi, Kolkata, Lucknow,
Pondicherry and Chandigarh were set up under the guidance and support of the Drug
Controller of India.
• India joined the WHO Programmed in 1997 for International Drug Safety Monitoring. The
programmed was managed Pharmacology, AIIMS) was considered as the National
Centre. The center in Mumbai (at KEM by the Uppsala Monitoring Centre, Sweden. The
center in New Delhi (at Dept of Hospital) was considered as the WHO Special Centre. Out
of the six centers, only the centers in Mumbai and New Delhi were actively working.
However, spontaneous reporting of ADRs.

24. • National Pharmacovigilance Advisory Committee based in the Central Drugs
Standard Control Organization (CDSCO), New Delhi started supervising the
NPVP.
• Two zonal centers. The South-West zonal centre and the North-East zonal
center, had been collecting information from all over the country and
sending the information to the Committee as wel as to the Uppsala
Monitoring Centre in Sweden.
• Mission of this program
• Safe guard health of Indians
• Ensuring benefit of medicine
• Out weight the risk associated with drug

25. Vision of pv program of India
• improve patient safety
• welfare of Indians health
Objective of pv program of India
• create nationwide system for patient safety reporting
• Identify and analyzed new ADR from reported cases
• Analyzed risk benefit ratio of marketed drug.
• Support regulatory agency in decision making
• Communicate safety info of medicine

26. Goal of PV program of India
they are devided into to type
• Short term
• Long term
Short term
• Develop and implement pv system
• Enroll all MCI approved medical colleges
• Encourage healthcare professional to report ADR of drug vaccine medical
devices and biological products
• Collection of case report and data

27. Long term
• Expand PV program to all govt. and privet hospitals
• Develop electronic reporting system
• Develop self-reporting culture among health professional
• To make ADR reporting mandatory for health professional
Causes of failure of implementation of PV program in India
• PV system not well funded and systematic for big country like India
• Data obtain from zonal to peripheral center are often poor and not well
analyzed
• Motivation for PV in healthcare professional in urban and ruler negligible
• Paitent not well educated to directly report ADR to regulatory bodies.

28. • Although clinical trials in India has been started in and around 1996. In global market the
landmark year for the industry was 2005. The studies of the clinical trials have been
structured, supervised where the safety and efficacy of a new drug or therapy are to be
tested to develop new treatments.
This would help those badly affected with the targeted condition. For conducting global
clinical trials, India is considered as a better choice for its
• Large patient populations,
• Highly educated talent,
• Wide spectrum of disease,
• Lower costs of operations,
• Favorable economic and intellectual property environment.

29. • Presently around the world the clinical research industry has grown at an
excellent rate with pharmaceutical industry. The major survival amount of
the pharmaceutical companies is innovation and introducing new drugs in
the market.
• For approval, well organized, properly supervised and well-structured clinical
trials have to be conducted as per ICH GCP guidelines and in accordance with
defined rules of the country wherein the trial is planned to be conducted.
• It should be mentioned here that the conditions under which patients are
studied during the pre-marketing phase do not necessarily reflect on how
these medicines will be used in the hospitals or in general practice once it is
marketed.

30. year Events
1747 First reported clinical trials by james lind , proving the effectiveness of
lemon juice in preventing survey
1937 Death of 107 children's due to sulfanilamide toxicity
1950 Aplastic anemia reported due to chloramphenicol
1961 Global disaster due to thalidomide toxicity
1963 16thWorld Health Assembly recognized importance to rapid action on
ADR's.
1968 WHO pilot research project for international drug monitoring.
1996 Clinical trials of global standards started in India.

31. 1997 India joined WHO Adverse Drug Reaction Monitoring Programme
1998 Pharmacovigilance initiated in India.
2002 67th National Pharmacovigilance Center established in India
2004-05 National Pharmacovigilance Programme launched in India
2005 Conduct of structured clinical trials in India.
2009-10 PVPI was initiated

32. Pharmacovigilance is also beneficial to the patients in the following means:
• It Increases the savings to the patient by cutting the cost,
• It helps the health care institution and other health care practitioners,
• It helps regulatory authority with respect to scrutiny or even the withdrawal
of drugs that do not show a favorable risk-benefit ratio.
• It can prevent from or reduces the readmissions of the patients.

33. INTRODUCTION TO ADVERSE DRUG
REACTIONS
• Adverse drug reactions (ADRs) is an unwanted, undesirable effect of a
medicine that occurs during usual clinical application. It occurs almost daily
in health care institutions and can adversely affect a patient’s quality of life;
sometimes may lead to considerable morbidity and mortality. Much
attention has been given to identify The patient populations most at risk, The
drugs most commonly responsible, andThe potential causes of ADRs.
• The factors responsible for the prevalence of ADRs worldwide are:
• Increase in the number of drugs in the market,
• An aging population, and
• An upward trend in polypharmacy.

34. • The difference between ADRS and ADES is that ADRs can occur even after
appropriate prescription and correct dosing. ADES are generally associated
with inappropriate use of the drug that usually occurs during drug therapy. It
may not be related to the pharmacology o the drug itself. Adverse drug
events (ADES) may occur due to medication errors. The National
Coordinating Council for Medication Error Reporting and Prevention (NCC
MERP) has defined the medication errors as: “any preventable event that
may cause or lead inappropriate medication use or patient harm while the
medication is in the control of the Health care professional, patient, or
consumer.

35. Objectives of ADRs Monitoring
• (A) To help the drug regulatory authority, public health programmes, scientists and
consumers for taking appropriate action to reduce the risks of ADRs. It is also necessary
to find out the nature and frequency of ADRs with periodical check of the benefit-risk
ratio of medicinal products. The benefit-risk ratio of medicinal products can be re for
evaluated by:
• Providing updated drug safety information to health care professionals and other
stakeholders includingWHO ADRs Monitoring Centers.
• Updating information in package and disseminating information which may result recall
or withdrawal of the product in the market or restrictions for marketing.
• Propagating information for designing proper education programme to consumers and
other users.
• Taking initiative to study the effect of a for further education. For example benefit of the
drug especially in long term for prevention of relapse or study of new indication,
overuse, possible mechanism underlying the adverse reaction observed or misuse.

36. • (B) To identify the risk factors that may affect, induce or influence the development,
severity and incidence of adverse reactions in the population; for example,
• 1 Patient factors such as genetics, racial differences, diets, diseases, prescribing
Practices, pattern of drug use and food habits (high carbohydrate, fat diet etc.).
• 2. Drug interactions, drug distribution, storage and use including indications, dose.
Availability and other underlying conditions.
• Due to adverse drug reactions the patients may lose confidence in the therapy or may
show negative towards their physicians and may look for self-treatment options. As a
result additional ADRS may not be observed. About 5% of the hospital admissions are
the result of an ADR, and at least one ADR would be found in about 10%-20% of
inpatients during their stay in hospitals. The actual frequency of ADRS may be even
greater than the above values. Because some ADRS imitate natural disease states and
thus, remain undetected and/or unreported

37. • Some ADRs present minor symptoms, others are serious and cause death in as many as
0.1%-0.3% of hospitalized patients.
• Adverse drug reactions should be identified and managed as early as possible to reduce
their harmful effects on the patients. The cost of managing ADRs can be high, whether
they occur in the inpatients or the outpatients. The clinical diagnosis of an ADR is not
always observable. Practitioners often advise Additional laboratory tests or procedures
to investigate the cause of a patient’s symptoms.
• Practitioners may also prescribe pharmacotherapy for conditions caused by an
unrecognized ADR. This increases the cost of treatment as well as the risk of additional
ADRs.
• If the ADR occurs when the patient is hospitalized, the duration of stay can be increased
and overall cost of treatment may also increase.
• Due to ADRs the anxiety or depression and loss of working days for the Patient and/or
Caregiver may take place, as a result additional indirect cost may increase.

38. • The study of drug-related injuries and making warning or withdrawal
recommendations for pharmaceutical agents are the major activities of
pharmacovigilance; however, it includes assessment, understanding, and
prevention ofADRs.
• Pharmacists play a vital role in each step of the pharmacovigilance activity; so
that the Patients need not require unnecessary procedures or take unnecessary
drugs so that safety And quality of life for the patient can be preserved.

39. Thank you