Pharmacovigilance is the science of monitoring the effects of medicines after they have been licensed for use, in order to identify new safety hazards and assess risks and benefits. It aims to improve patient care and safety in relation to medicine use. The thalidomide disaster in the 1960s demonstrated the need for formal pharmacovigilance systems to detect adverse drug reactions. Spontaneous reporting by healthcare professionals and mandatory reporting by manufacturers are key methods for collecting information on adverse drug events. Reports are assessed for causality and contribute to the ongoing evaluation of medicines to ensure their safe and effective use.

1. Dr. Barathane
PHARMACOVIGILANCE

3. WHAT IS PHARMACOVIGILANCE ?
Pharmaco + Vigilance
Derived from greek
Pharmaco – Medicine
Vigilare – To watch
The process of paying close and continuous attention

4. DEFINITION
Pharmacovigilance is the science and activities relating to the
Detection
Assessment
Understanding and
Prevention
of adverse drug reaction or any other possible adverse drug related problems
“ Recently, its concerns have been widened to include herbals, traditional and
complementary medicines, blood products, biologicals, medical devices and
vaccines”
WHO 2002

5. AIMS OF PHARMACOVIGILANCE
• Improve patient care and safety in relation to the use of
medicines, and all medical and paramedical interventions
• Improve public health and safety in relation to the use of
medicines
• Contribute to the assessment of benefit, harm, effectiveness
and risk of medicines, encouraging their safe, rational and more
effective (including cost-effective) use
• Promote understanding, education and clinical training in
pharmacovigilance and its effective communication to the public.

6. NEED OF PHARMACOVIGILANCE
Reason 1: Humanitarian concern
• Insufficient evidence of safety from clinical trials
• Tests in animals are insufficient to predict human safety
• Safety profile in special groups (elderly, parous
women,childern) inadequate / Incomplete
Reason 2: Ethics
Known to cause harm and not informing the patient is
unethical

7. Reason 3: Medicines are supposed to save lives
‘Dying from a disease is sometimes unavoidable;
dying from a medicine is unacceptable’ Lepakhin V. Geneva
2005
ADRs were 4th-6th commonest cause of death in the US in 1994
Lazarou et al, 1998

8. Reason 4: ADRs are expensive !!
• Cost of drug related morbidity and mortality exceeded $177.4
billion in 2000 (Ernst FR & Grizzle AJ, 2001: J American
Pharm. Assoc).
• ADR related cost exceeds the cost of the medications
themselves.
Reason 5: Promoting rational use of medicines and adherence
Reason 6: Ensuring public confidence

9. EVOLUTION OF PHARMACOVIGILANCE
1934-1960
Period of Drug Explosion

10. USA
Diethyleneglycol (DEG)
Mistakenly used to solubilize Sulphanilamide
107 died

11. The Thalidomide Disaster
1956
Thalidomide launched in market
1959-61
Reports of foetal abnormalities (20,000 cases
)
(maximum in Germany)

12. 1962
USA revised law requiring to prove safety and efficacy before issuing
marketing authorization
1963
British committee on safety of drug monitoring
1964
UK starts the “YELLOW CARDS” system
1964-65
National ADR reporting system
UK, Australia, New Zeland, Canada, West Germany, Sweden
1978
WHO center moved from GENEVA to UPPSALA

13. THALIDOMIDE (1961) Congenital limb defects
BENOXAPROFEN (1982) Hepatotoxicity
PHENFORMIN (1982) Lactic acidosis
FENFLURAMINE (1997) Heart-valve abnormalities
ASTEMIZOLE Many drug interactions
PHENYLPROPANOLAMINE(2000) Haemorragic stroke
CERIVASTATIN Rhabdomyolysis
CISAPRIDE Cardiac arrythmias
ROFECOXIB (2004) Cardiovascular events
VALDECOXIB (2005) Cardiovascular events,
TEGASEROD (2007) Cardiovascular events
CLOBUTINOL (2007) Cardiac arrhythmia
DRUGS WITHDRAWN FROM MARKET

14. TERMINOLOGIES IN PV
Adverse Drug Reaction (ADR)
A response to a medicine which is noxious and unintended, and which occurs at
doses normally used in man
Adverse Drug Event (ADE)
Any untoward medical occurrence that may present during treatment with a
medicine but which does not necessarily have a causal relationship with this
treatment
Side Effects
Any unintended effect of a pharmaceutical product occurring at doses normally
used by a patient which is related to the pharmacological properties of the drug

15. Unexpected Adverse Drug Reaction
An adverse reaction, the nature or severity of which is not consistent with
domestic labelling or market authorisation, or expected from characteristics of
the drug
Serious Adverse Drug Event / Reaction
Untoward medical occurrence that at any dose:
• Results in death
• Requires inpatient hospitalization or prolongation of existing hospitalization
• Results in persistent or significant disability / incapacity
• Is life-threatening

16. CLASSIFICATION OF ADRS
(RAWLIN AND THOMPSON CLASSIFICATION)
• Type A - Dose related – expected – extension of pharmacological effects
Salbutamol and tachycardia
• Type B - Non dose related – bizarre – more serious
Penicillin rash
• Type C - Dose and time related – related to cumulative drug use
NSAID’s induced Nephropathy
• Type D - Delayed effects – carcinogenesis and teratogenicity
Thalidomide and phocomelia
• Type E - End-of-use - due to withdrawal
Addisonian crisis after steroid withdrawal
• Type F - Failure of therapy
Prescription, diagnosis, missed selection of the medicine or doses.

17. SEVERITY OF ADR’S
• Minor: No need of therapy, antidote, or hospitalization
• Moderate Requires drug change , specific treatment,
hospitalization
• Severe Potentially life threatening; permanent
damage, and prolonged hospitalization.
• Lethal Directly or indirectly lead to death

18. IS IT AN ADR?
• Take a Proper History and do a relevant examination
• Establish time relationship : Some response are quick / delayed.
Logical relation between initiation
of therapy and appearance of ADR
• Do a thorough physical examination with appropriate laboratory
investigations
• Effect of Dechallenge and Rechallenge should be determined
• Literature search of the Medicine which caused the ADR

20. DIFFERENT SCALES FOR CAUSALITY ASSESSMENT
• Naranjo’s algorithm
• Kartch Lasagna`s algorithm
• WHO probability scale
• Spanish quantitative imputation scale
• Kramer's scale
• Jones scale
• European ABO system
• Bayesian system

23. INTERPRETATION TO TOTAL s
• Total scores of 9 or more mean that ADR is highly probable
• Scores from 5 to 8 mean that ADR is probable.
• Scores from 1 to 4 that ADR is possible.
• Scores of zero or less mean that ADR is doubtful

24. PHARMACOVIGILANCE PROCESS
1. Detecting and Reporting an ADR
ADR form is filled out with the patient and reaction details
in the prescribed format
• Spontaneous reporting
• Mandatory reporting

25. Spontaneous reporting
• Most common form of ADR reporting
• Healthcare professionals identify and report any suspected
adverse drug reaction to their National Pharmacovigilance
Centers
Mandatory reporting
• Manufacturers are required to submit reports they receive
from healthcare providers to the National Authority, in the
form of a PSUR (Periodic Safety Update Report)
• A regulatory document prepared by the Marketing
Authorisation Holder & submitted to the Agency

26. COMPARATIVE
OBSERVATIONAL STUDIES
• Cross sectional survey
• Case control study
• Cohort studies
• Large safety trial
• Drug utilization study
ACTIVE SURVEILLANCE
• Site surveillance (hospitals,
pharmacies, nursing homes
etc.)
• Focused ADR monitoring of
drugs
• Prescription event
monitoring
• Disease registries from
Public health Programme
OTHER METHODS FOR COLLECTING ADR

27. WHO CAN REPORT AN ADR
ManufacturerDentistPharmacist
Doctor Nurse Others

28. STAKEHOLDERS IN PV
• Government
• Industry
• Hospitals and academia
• Medical and pharmaceutical associations
• Poisons information centres
• Health professionals
• Patients
• Consumers
• Media
• WHO

29. FACTORS TO BE REPORTED
• Report all suspected reactions including minor ones in case of new
drugs
• For established or well known drugs - All serious, unexpected,
unusual ADRs
• ADRs to generics not seen with innovator products
• ADRs to traditional medicines
• All suspected drug-drug, drug-food, drug-food supplement interactions
• ADRs associated with drug withdrawals
• ADRs due to medication errors
• ADRs due to lack of efficacy or suspected pharmaceutical defects

30. HOW TO REPORT
Different forms have been developed for reporting ADR’s:
• MEDWATCH by FDA
• YELLOW CARD
• Submitting forms to the nearest national
Pharmacovigilance centers

31. WHEN TO REPORT
Timeline of reporting an ADR
• By the sponsor to Licensing Authority – 14 calendar days
• Investigator to the sponsor within 24 hours
• Investigator to the Ethics Committee within 7 working days

32. WHERE TO REPORT
• WHO & UMC • Uppsala Monitoring Centre (UMC) - is responsible for the
management of the WHO program for International Drug Monitoring
• Computer software for case report management designed to suit the needs
of National Centers (Vigiflow)
FUNCTIONS OF UMC
• To co-ordinate the WHO program for international drug monitoring and its
member countries
• To collect, assess and communicate information from member countries
about the benefits, harms and risks of drugs and other substances used in
medicine to improve patient therapy and public health worldwide
• To collaborate with member countries in the development and practice of the
science of pharmacovigilance

33. Pharmacovigilance in UK
• Yellow Card Scheme
• ADROIT – Adverse Drug Reactions Online Information Tracking
system.
Pharmacovigilance in USA
• MEDWATCH
• MEDWATCH 3500 form / FDA form 3500
Pharmacovigilance in India
• Central Drugs Standard Control Association – DGHS, Ministry of
Health & Family Welfare
• Legislative requirements of PV in India – Schedule Y of the
drugs & cosmetic act 1945

34. INDIAN SCENARIO
• No Formal PVG system initially - sourced their safety
assessment of drugs on data derived US, EUROPE &
JAPANESE MARKETS.
• 1986 - Formal PVG activities were initiated
• 1997 – India joined the Adverse Drug Reaction Monitoring
Programme of WHO.
• 2004 –2008 National Pharmacovigilance Prog. (2 Zonal, 5
Regional, 24 Peripheral Centers)
• Due to some technical difficulties the NPP had to be closed in
2008
• It was again resurrected as the PHARMACOVIGILANCE
PROGRAMME OF INDIA (PvPI) In 14/07/2010 @ AIIMS

35. For more effective implimentation of the programme the center was shifted from
AIIMS to INDIAN PHARMACOPOEIA COMMISSION, GHAZIABAD on
15/04/2011.

36. AIMS & OBJECTIVES
Aim:
• To ensure that the benefits of use of medicine
outweighs the risks and thus safeguard the health of
the Indian population

37. Objectives :
• To monitor Adverse Drug Reactions (ADRs) in Indian population
• To create awareness amongst health care professionals about
the importance of ADR reporting in India
• To monitor benefit-risk profile of medicines
• Generate independent, evidence based recommendations on
the safety of medicines
• Support the CDSCO for formulating safety related regulatory
decisions for medicines
• Communicate findings with all key stakeholders
• Create a national centre of excellence at par with global drug
safety monitoring standards

39. A. Patient information
B. Suspected adverse reaction
• Date when started and
recovered
• Reaction description
C. Suspected medication
D. Reporters information

41. NUMBER OF ADR MONITORING CENTRES
• SOUTH ZONE-25 AMC’S
• NORTH ZONE-28 AMC’S
• WEST ZONE-20 AMC’S
• EAST ZONE-17 AMC’S.