This document discusses pharmacovigilance and the need for monitoring drug safety post approval. It describes how historical drug safety issues like the Elixir Sulfanilamide and Thalidomide tragedies revealed limitations in pre-approval testing and established the need for ongoing pharmacovigilance. The aims, application and reporting processes of pharmacovigilance are outlined along with terminology and examples of regulatory actions taken based on adverse event reporting.

1. PRESENTED BY
S.NIKHIL
DEPARTMENT OF PHARMACEUTICS
PE/2017/315

2.  INTRODUCTION
 AIMS OF PHARMACOVIGILANCE
 NEED FOR PHARMACOVIGILANCE
 APPLICATION OF PHARMACOVIGILANCE
 REPORTING OF ADR
CONTENTS
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3. Pharmacovigilance (PV) is defined as the science and activities relating
to the detection, assessment, understanding and prevention of adverse
effects or any other drug-related problem.
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INTRODUCTION:
Pharmacovigilance starts from clinical stage and continues throughout the
product life cycle

4. Taste of Raspberries, Taste of Death
The 1937 Elixir Sulphanilamide Incident
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Bristol company formulated Sulphanilamide elixir with
diethylene glycol as solvent
 The elixir was tested for the flavor, appearance, fragrance but
not for toxicity
Solvent led to death of >100 people
The drug and the deaths led to the passage of the 1938 Food,
Drug, and Cosmetic Act, which increased FDA's authority to
regulate drugs

5. THE THALIDOMIDE TRAGEDY
 Use : Morning sickness
Medical disaster ever, where over 10,000 children
were born with malformations In 1961
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6. 6
16th world assembly adopted
a resolution.. New system
developed for detecting ADR
Science of
PHARMACOVIGILANCE

7. 7
Clinical trials fail
to identify side-
effects that are
rare
side-effects do
not occur in the
context of clinical
trials
lack of a suitable
detection
techniques
Need
NEED FOR PHARMACOVIGILANCE

8. POPULATIONS NOT STUDIED IN THE PRE-APPROVAL
PHASE
• Children
• The elderly
• Pregnant or lactating women
• Patients with relevant co-morbidity
• Patients with disease severity different from that studied in clinical trials
• Patients of different races
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9. 9

10. 10
Pharmaco-vigilance
National
Pharmaco-
vigilance
Centre
Uppsala
monitoring
centre
Hospitals,
Health
professional,
Patients
WHO
quality
assurance
and safety
team

11. APPLICATION OF PHARMACOVIGILANCE
 PHARMACOVIGILANCE in drug regulation
 PHARMACOVIGILANCE in clinical practise
 PHARMACOVIGILANCE in international health
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12. TERMINOLOGIES
Absolute risk Risk in a population (e.g. 1 in 1,000).
Adverse Event (AE) Any untoward medical occurrence that may present
during treatment with a pharmaceutical product but which does not necessarily
have a causal relationship with this treatment.
Adverse (Drug) Reaction (ADR) A response which is noxious and unintended,
and which occurs at doses normally used in humans for the prophylaxis,
diagnosis, or therapy of disease, or for the modification of physiological
function. (WHO, 1972).
Causal relationship A relationship between one phenomenon or event (A) and
another (B) in which A precedes and causes B. In pharmacovigilance; a
medicine causing an adverse reaction.
Causality assessment The evaluation of medicine was the causative agent of an
observed adverse reaction.
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13. Efficacy
The ability of a drug to produce the intended effect as determined by
scientific methods, for example in pre-clinical research conditions
(opposite of hazard)
Harm
The nature and extent of actual damage that could be caused by a drug.
Not to be confused with risk
Periodic Safety Update Report (PSUR)
A systematic review of the global safety data which became available to the
manufacturer of a marketed drug during a specific time period
Cohort Event Monitoring
observational study of events that occur during the use of medicines
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14. Relative risk
Ratio of the risk in an exposed population (absolute risk) and the risk in an unexposed
population (reference risk). Relative risk is the result of a relative comparison between
outcome frequency measurements, e.g. incidences.
Risk
The probability of harm being caused; the probability (chance, odds) of an
occurrence.
Serious Adverse Event or Reaction
A serious adverse event or reaction is any untoward medical occurrence that at any
dose:
 results in death
 requires inpatient hospitalization or prolongation of existing hospitalization
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15. Signal
Reported information on a possible causal relationship between an adverse
event and a drug, the relationship being unknown or incompletely
documented previously
Summary of Product Characteristics (SPC)
A regulatory document attached to the marketing authorization which
forms the basis of the product information made available to prescribers
and patients
Spontaneous reporting
System whereby case reports of adverse drug events are voluntarily
submitted from health professionals and pharmaceutical manufacturers to
the national regulatory authority
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16. • SUSAR
• A suspected unexpected serious adverse reaction (SUSAR) is any UAR
that at any dose:
• a. Results in death;
• b. Is life threatening (i.e. the subject was at risk of death at the time of the
event)
• c. Refer to an event which hypothetically might have caused death if it
were more severe
• d. Requires hospitalization or prolongation of existing hospitalization;
• e. Results in persistent or significant disability or incapacity;
• f. Is a congenital anomaly or birth defect.
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17. • Summary of identified risks of drugs and potential risks
missing information
• Serves Basis for action plan for pharmacovigilance and
risk management plan
Active
surveillance
Epidemiological
studies
Further Clinical
studies
drug utilization
studies
ACTION PLAN IN RMP
RISK MANAGEMENT PLAN
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18. Additional educational material about the medicine and its use
Training programs
Restricted use of the medicine
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If the action plan specifies additional risk minimization
activities, these could include

19. TYPES OFADR
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20. REPORTING OF ADR
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21. How to report?
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Report serious adverse reactions. A reaction is serious when the patient
outcome is
1. life-threatening (real risk of dying)
2. hospitalization (initial or prolonged)
3. disability (significant, persistent or permanent
4. congenital anomaly
Who can report
Any health care professional (Doctors including dentists, Nurses and Pharmacists)

22. Where to report?
• Adverse drug reaction Monitoring Centre (AMC) or to
• National Coordinating Centre
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What happens to submitted form?
 Causality assessment of medicines done in AMC WHO-UMC scale
 Analyzed report are sent to NCC through ADR database
Finally database analyzed and forwarded to global Pharmacovigilance
database (WHO UPPSALA centre in Sweden)

23. REPORTING OF ADR
• INDIA
• UK(Yellow card)
• US (Medwatch)
• AUSTRALIA(Blue card)
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24. OUTCOMES OF PHARMACOVIGILANCE
• Reduces risk of ADR
• Rational use of medicines
• Assessing drug safety
• Label change(if necessary)
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25. CASE STUDY
• 1980s pfizer developed drug for hypertension and angina efficacy was minimal
• Found erection in impotent male who are taking this treatment
• In jan 1997 they conducted study involving 3,000 subjects ages 19 to 87
• In march 1998 they got approval for oral therapy by FDA
• Despite wide spreading adoption caused small no.ofdeaths in 6months in 6millions
prescription dispensed
• FDA received deaths of 130 in that 77 are cardio related problems
• They found interaction with nitrates
• FDA ordered pfizer to amend label on this thing
• In july 2005 FDA received reported on small number men lost eye sight and label
was changed
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26. NEW DRUG ALERTS
• UK
• INDIA
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27. OUTCOME OF PHARMACOVIGILANCE PROGRAMME OF INDIA
SN.O DRUGS ADVERSE REACTION RECOMMENDATION OF
PVPI TO CDSCO
CDSCO INITIATIVE
1 Lamotrigine Steven johnson syndrome For label change In process
2 Ceftriaxone Steven johnson syndrome For label change In process
3 Betamethasone Photosensitivity reaction For label change In process
4 Surfactant Pulmonary hemorrhage For label change In process
5 Ranitidinde Cardiac arrest For label change In process
REGULATORY ACTION ON BASIS OF ADR REPORT
SN.O DRUG ADR CDSCO action
1 Carbmazepine Stevens johnson syndrome and toxic
epidermal necrolysis
CDSCO instructed marketing
authorizing holder(mah) to comply the
same
2 Mannitol Hypokalaemia Approved in subject expert
committee (SEC) of CDSCO
3 Rotavirus vaccine Intussusception Approved in SEC of CDSCO
4 Piperacillin & tazobactum Hypokalemia and bronchospasm CDSCO instructed to MAH comply
with the same
5 Anti rabies vaccine Erythema multiforme CDSCO instructed to MAH to comply
with the same
On the basis of PVPI recommendations CDSCO has taken action
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29. CONCLUSION;
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 Important for healthcare professional to know about each drug data
documentation , drug benefit ratio profile
 Knowing about every step of pharmaceutical management cycle
advantageous for health organization to educate patient clearly about every
drug

30. REFERENCES
 Amery, W. K. (1999). Why there is a need for
pharmacovigilance. Pharmacoepidemiology and drug safety, 8(1), 61-64.
 World Health Organization. (2002). The importance of pharmacovigilance
 http://www.ipc.gov.in/PvPI/pv_home.html
 Biswas, P. (2013). Pharmacovigilance in Asia. Journal of Pharmacology &
Pharmacotherapeutics, 4(Suppl1), S7–S19. Kumar, L. (2015).
 Lokesh ,.Pharmacovigilance/reporting adverse drug reactions: an approach to
enhance health surveillance and extending market share by minimizing the
chances of drug withdrawals. International Journal of Pharmacy and
Pharmaceutical Sciences, 7(9), 1-7.
 https://helix.northwestern.edu/.../thalidomide-tragedy-lessons-drug-safety-and-
regulati..
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31.  https://www.fda.gov/aboutfda/whatwedo/history/.../sulfanilamidedisaster/
 www.fda.gov/safety/medwatch/howtoreport/downloadforms/default.
 uk.gov(drug safety updates)
 https://www.pfizer.com/files/health/.../22_What_is_a_Risk_Management_Plan
.pdf
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