An introduction History Of pharmacovigilance and its Adverse Event reporting Regulatory Bodies & Guidelines For Pharmacovigilance.

1. Dhiraj B. Malekar

2. ◾1937-sulfanilamide disaster (poisoningof
children)
◾1938 Federal, food, drug, and cosmeticsAct.
◾1961-Thalidomidedisaster (birth defects)
◾Question arises for drug safety

3. 1959 – 1961 thalidomide 4,000 - 10, 000 cases of
phocomelia (congenital limb defects)
This lead to withdrawal of the drug from the market

4. ◾Started 1968
◾Located inUppsala,Sweden
◾Collaborating centre for maintaining
globalADR database -Vigibase

5. 1. Thalidomide (1965) Phocomelia
2. Practolol (1975) Sclerosing
3. Phenformin (1982)
peritonitis
Lactic acidosis
4. Rofecoxib (2004) cardiovascular
effects
5. Veralipride (2007) Anxiety,
depression,
movement disorders
6. Rosiglitazone (2010( Increased risk of
MI and death
from CV causes

7. Reason 1: Insufficient evidence of safety
◾Animal experiments
◾Clinical trials prior to marketing
Reason 2: Dying from a disease may be
inevitable, dying from a medicineis
unacceptable (WHO,2005)
Reason 3:ADR are expensive

8. ◾To improve patient care and safety
◾To improve public health and safety
◾To contribute to the assessment of benefit,
harm, effectivenessand risk of medicines
◾To promote understanding, education and
clinicaltraining

9. ◾ Adverse Drug Reaction
 "A response to a drug which is noxiousand unintended, and which
occurs at doses normally used in man for the prophylaxis,
diagnosis, or therapy of disease, or for the modification of
physiological function."
◾ Adverse Event
 Any untoward medical occurrence that may present during
treatment witha pharmaceutical product butwhich does not
necessarily have a causal relationship withthis treatment
◾ Side Effect
 Any unintended effect of a pharmaceutical product occurring at
doses normally used in man which is related to the
pharmacologicalproperties of the drug

10. Before drugs become available to the patients,
they are subjected to rigorous clinical studies.
However, some adverse drug reactions (ADRs)
are often detectedONLY after marketing.

11. 1. All suspected reactions including minor ones
2. All serious, unexpected, unusual ADRs
3. Change in frequency of a given reaction
4. All suspected drug-drug, drug-food, drug food
supplements interactions
5. ADRs associated with drug withdrawal
6. ADRs due to medication errors
7. ADRs due to lack of efficacy or suspected
pharmaceutical defect

12. ◾Patient
◾Suspect drug
◾Reporter
◾Adverse event

13. 1. TypeA: Augmented pharmacologic
effects (dose dependent and
predictable)
2. Type B: Bizarre effects (dose independent
& unpredictable)
3. TypeC: Chronic effects
4. Type D: Delayed effects
5. Type E: End-of-treatment effects
6. Type F: Failure of therapy
7. TypeG: Genetic reactions

14. Serious (FDA): when the patient outcome:
1. Death
2. Life-threatening
3. Hospitalization
4. Disability - or permanent change, impairment, damage or
disruption in the patient's body function/structure, physical
activities or quality of life
5. Congenital abnormalities
6. Requires intervention to prevent permanent damage
Severity: intensity of the adverse effect

15. 1. Intrinsic
Idiosyncrasy Mutagenicity
CarcinogenicityTeratogenicity
2. Extrinsic
Adulterations, contamination
3. Underlying medical conditions
4. Interactions
5. Wrong use

16. ◾Unsolicited reports (spontaneous, literature,
media)
◾Solicited reports (PSP,organization,
Pharmacy,etc)

17. ◾Patients, patients relatives or patients
carers
◾Health care professionals (physicians,
dentists, pharmacists, radiographers,
nurses)
◾Manufacturers
◾Authorities

18. ► RegulatoryAuthority
► Industry, manufacturers
► Health professionals
► Patient organizations
► General public
► Social security

19. ◾ For abnormalities not found in theToxicityTables,
the following scale will be used to estimate grade:
 Grade 1, Mild:Transient or mild discomfort; no limitation
in activity; no medical intervention/therapy required
 Grade 2, Moderate: Mild to moderate limitation in activity
–some assistance may be needed; no or minimal medical
intervention/therapy required

20.  Grade 3, Severe: Marked limitation in activity, some
assistance usually required; medical intervention/therapy
required and hospitalization possible
 Grade 4, Life-Threatening: Extreme limitation in activity,
significant assistance required; significant medical
intervention/therapy required; hospitalization or hospice
care probable
◾ Any event deemed by the clinician to be serious or
life threatening should be considered a Grade 4

21. How likely is this medicationthe cause of
this problem in this particular patient?

22.  Causality Assessment Scales
 Naranjo's scale
 WHO probability scale
 Karch & Lasagna scale
 Spanish quantitativeimputation
scale
 Kramer's scale
 EuropeanABO system
 Jones scale
 Bayesian system

24. 1. Are there previous conclusive reports on this
reaction?
2. Did the adverse event appear after the suspected
drug was given?
3. Did the adverse reaction improve when the drug
was discontinued or a specific antagonist was
given?
4. Did the adverse reaction appear when the drug was
readministered?
5. Are there alternative causes that could have caused
the reaction?

25. 6. Did the reaction reappear when a placebo was
given?
7. Was the drug detected in any body fluid in toxic
concentrations?
8. Was the reaction more severe when the dose was
increased, or less severe when the dose was
decreased?
9. Did the patient have a similar reaction to the same
or similar drugs in any previous exposure?
10. Was the adverse event confirmed by any objective
evidence?

26. DefiniteADR > 9
ProbableADR 5-8
PossibleADR 1-4
DoubtfulADR 0

27. Certain
Probable
Possible
Unlikely
Conditional
Unclassifiable

28. ◾TheYellowCard Scheme is theUK system for
collecting information on suspectedADRs.
◾TheScheme was founded in 1964 after the
thalidomidedisaster.

29. 1. Patient details
2. Suspected drug
3. Suspected reaction
4. Reporter details

31. INTERNATIONAL ORGANIZATIONS
World Health Organization (WHO)
Pan American Health Organization (PAHO)
World Trade Organization (WTO)
International Conference on Harmonization (ICH)
World Intellectual Property Organization (WIPO)

32. Country Name of Regulatory Authority
USA Food and Drug Administration (FDA)
UK Medicines and Healthcare Products Regulatory Agency (MHRA)
Australia Therapeutic Goods Administration (TGA)
India Central Drug Standard Control Organization (CDSCO)
Canada Health Canada
Europe European Medicines Agency (EMEA)
Denmark Danish Medicines Agency
Costa Rica Ministry of Health
New Zealand Medsafe - Medicines and Medical Devices Safety Authority
Sweden Medical Products Agency (MPA)
Netherlands Medicines Evaluation Board
Ireland Irish Medicines Board
Italy Italian Pharmaceutical Agency
Nigeria National Agency for Food and Drug Administration and Control (NAFDAC)
Ukraine Ministry of Health
Singapore Centre for Pharmaceutical Administration Health Sciences Authority
Hong Kong Department of Health: Pharmaceutical Services
Paraguay Ministry of Health
Sweden Medical Products Agency (MPA)
Thailand Ministry of Public Health
China State Food and Drug Administration
Germany Federal Institute for Drugs and Medical Devices
Malaysia National Pharmaceutical Control Bureau,Ministry of Health
Pakistan Drugs ControlOrganization, Ministry of Health
South Africa Medicines ControlCouncil
Sri Lanka SPC,Ministry of Health
Switzerland Swissmedic , Swiss Agency for Therapeutic Products
Uganda Uganda National Council for Science and Technology (UNCST)
Brazil Agencia Nacional de Vigiloncia Sanitaria (ANVISA )
Japan Ministry of Health, Labour & Welfare(MHLW)

33. ◾ICHGCP guideliness (E,Q,S, & M)
◾EMA guideliness (Volumes)