This ppt contains detailed information of pharmacovogilance

1. Pharmacovigilance
DR. VEENA RANI VEMURI
Associate Professor
Department of Pharmacology

2. LEARNING OBJECTIVES - ADR
Explain the impact that Adverse Drug Reactions (ADRs) have on morbidity and
Explain the role and function of the Indian Pharmacovigilance Centre (PvPi) and how
pharmacovigilance contributes to the safe use of medicines
Identify situations when an ADR report should be submitted
File a completed report
Describe general principles and strategies to prevent or minimize harm from ADRs

3. Content of the Session
What is pharmacovigilance?
Why do we need pharmacovigilance?
Definitions of AE,SAE,ADR.
Vaccine PV
Your role-:Why, what and How to report in case of AE/SAE/ADR?
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4. What is Pharmacovigilance ?
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.
Monitor in real time the benefit-risk ratio of the drugs.
Harmonize and centralize safety data to facilitate the identification of risks associated with
products
Communicating the risks and risk minimization measures associated with products to HCPs
(Healthcare Professionals) and Patients/consumers.
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5. 5
 The central drugs standard control organization (CDSCO), New Delhi, under the
aegis of the Ministry of health & family welfare, the government of India has
initiated a nationwide pharmacovigilance Program (PvPi) and Indian Pharmacopoeia
Commission (IPC), Ghaziabad, (U.P.) Is a national co-ordinating center for the
program.
 The pharmacovigilance program of India (PvPi), mission is to safeguard the health
of the Indian population by ensuring that the benefit of the use of medicine
outweighs the risks associated with its use.
 Pvpi has succeeded in establishing 395 adverse drug reaction monitoring centers
(AMC) across the country. Currently, pvpi ranks 9th in reporting of ICSRs to WHO-
UMC.

6. WHY PHARMACOVIGILANCE
Pharmaceutical companies are required by law in all countries to report ADRs during clinical trials, testing new drugs
on people before they are made generally available.
Because these pre-registration clinical trials involve only several
thousand patients at most, less common ADRs are often unknown
when a drug enters the market.

7. Thalidomide disaster
Rofecoxib Withdrawal
Benfluorex (Mediator) withdrawal
Lots of drugs entering the market, the tendency to self-medicate,
herbal medicines, OTC medicines.
There is also the issue of off-label use, a drug used in unapproved
indications which needs to be addressed from a safety perspective.
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WHY PHARMACOVIGILANCE

8. Objectives of Pharmacovigilance
Detection of Risk Factors
Early Identification of Unknown Safety Problems
Quantifying the Probability of Risk
Measurement of Effectiveness

9. Importance of Pharmacovigilance
To improve the patient's safety.
Providing reliable information for the efficient assessment of the risk-benefit profile of medicines.
Encouraging the safe, rational, and more effective (including cost-effective) use of various
medicines.
Promote education, understanding, and clinical training in pharmacovigilance and its effective
availability to the public.

10. Definitions of AE/SAE/SUSAR : 1/3
Adverse Events/Adverse drug reaction are also known as side effect, problems, issues associated with medical
product by patients/consumers in laymen’s language.
They are important elements in PV as this form data source in assessing the risks associated with medicinal
product.
1. Side effect: Unintended effect occurring at normal dose related to the pharmacological properties.
2. Adverse Event: Any untoward medical occurrence in a patient or clinical investigation subject administered
a pharmaceutical product and which does not necessarily have to have a causal relationship with this
treatment.
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11. Definitions of AE/SAE/SUSAR : 2/3
3. Adverse drug reaction: Any noxius change which is suspected by the reporter or the manufacturer as
being related to the study drug, occurs at NORMAL doses used in humans which requires either treatment or
stoppage of drug or caution to use same drug for its future use .
4. Causality: Causality assessment essentially means finding a causal association or relationship between a
drug and drug reaction. Various methods of causality are available WHO-UMC, Naranjo scale, etc . Causality
opinions can be based on different criteria such as: the timing of the event in relation to drug intake, the
nature of the event, similarity to events with other drugs in the class, medical history, concurrent conditions
of patient.
5. AEFI: Adverse Event following Immunization: Adverse event following immunization is any untoward
medical occurrence which follows immunization and which does not necessarily have a causal relationship
with the usage of the vaccine. If not rapidly and effectively dealt with, can undermine confidence in a vaccine
and ultimately have dramatic consequences for immunization coverage and disease incidence.
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12. Definitions of AE/SAE/SUSAR : 3/3
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7. Suspected Unexpected Serious Adverse Reaction (SUSAR): it is defined as below:
Suspected: Causality is assessed as Reasonable possibility that the event is due to the study drug.
Unexpected: An unexpected adverse event that is not identified in nature, severity, or frequency in the current
Investigator’s Brochure/USPI/Package insert/SmPC.
6. A Serious Adverse Event (SAE) : It is defined as an untoward medical occurrence that at any dose:
•Results in death;
•Is life-threatening;
•Requires in-subject hospitalization or prolongation of existing hospitalization;
•Results in persistent or significant disability/incapacity;
•Is a congenital anomaly/birth defect; and/or
•Other medically Important condition /Medically Significant
Seriousness is a criteria defined by legislation and severity is stated by the reporting physician in order to state the intensity
of the adverse event. Hence a treating physician/investigator’s assessment is mandatory.

13. Reporting tools
Available
1. Suspected ADR reporting FORM
(version 1.4)
2. AEFI – Adverse event following
immunization case notification
FORM
3. TRRF - Transfusion reaction
reporting FORM
4. Medical device Adverse event
reporting FORM
5. Medicine side effects reporting
FORM (for consumers)

14. 1. Suspected ADR reporting FORM (version 1.4)
ADR_Reporting_For
m_1.4_Version.pdf (
ipc.gov.in)

15. 2. AEFI – Adverse event following immunization
https://ipc.gov.in/images/pdf/File6
50.pdf

16. 3. TRRF -
Transfusion
reaction
reporting
form
https://nib.gov.in/Haemovigilance/
TRRF_Form_new.pdf

17. 3. TRRF -
Transfusion
reaction
reporting
form
https://nib.gov.in/Haemovigilance/
TRRF_Form_new.pdf

18. 4. Medical device and Materiovigilance programme
https://ipc.gov.in/images/MEDICAL_DEVICE_ADVERSE
_EVENT_REPORTING_FORM_editable.pdf

19. 4. Medical device and Materiovigilance programme
https://ipc.gov.in/images/MEDICAL_DEVICE_ADVERSE
_EVENT_REPORTING_FORM_editable.pdf

20. 5. Medicine side effects reporting form for consumers
https://ipc.gov.in/images/pdf
/File492.pdf

21. Why should HCPs report adverse event?
All HCPs can report adverse events (including pharmacists, nurses, lab. technicians,
doctors, students) even patients and consumers can report too.
There is no legal obligation or action for reporting, nor there is any fee to be paid or
earned.
Reporting an adverse event will help bring safer and more effective drugs for
patients.
HCPs will have more information about drugs, indications, contraindications,
warnings, precautions, and how to anticipate and treat if an adverse event occurs in
the patient.
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22. What happens to reported AE data?
Patients/Consumer/HCP
Pharma companies/Medical college/Health authority (PvPI)
Health
Authorities/WH
O-UMC
Investigator/HCP/Pharmacist
Data Management
Medical review
Patient/Consumers
Communication for safe use of drug via
Package insert
USPI/SmPC
Dear HCP letter
Trainings/CME
Social Media messages
Actions
Pharmacovigilance Team
Adverse events occurs
Safety report forms
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23. What happens to
reported AE data?
Ø Package insert
Ø Risk minimization measure
Ø Patient leaflets
Ø HCP Training and leaflets
Ø More studies
Ø Collection and monitoring

24. Vaccine PV
Corona vaccine is our current blockbuster movie. Why? As we need an effective vaccine which will help us
have our pre corona life back.
We have only approx. 30 vaccines meaning only 30 diseases can be prevented as opposed to more than 20
thousand drugs.WHO Recommends 15 vaccines currently for routine vaccination and 10 for selected usage.
Almost two dozen vaccines now have been authorized around the globe; many more remain in development
(apprx 80).In India, Covisheild and Covaxin.By the end of 2021, India might have access to 6 COVID-19
vaccines, all in the pipeline and being locally developed.
Passive surveillance systems (or spontaneous reporting systems) is cornerstone for monitoring vaccine
surveillance.
AEFI programs are mainstay in terms of ensuring vaccine safety

25. What and When AE information should be reported by HCP?
For regulatory reporting, the minimum data elements for a initial notification of an SAE are:
An identifiable reporter
An identifiable patient
An adverse reaction
A suspect drug (Investigational product as per clinical study protocol/marketed product or
products)
Complete AE form data as much is available on the form
As soon as possible but within 15 days after you become aware of the adverse event (non-
fatal and non-life-threatening)
As soon as possible but within 7 days after you become aware of the adverse event (for a
fatal or life-threatening)
As soon as possible
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26. FUNCTIONS OF A PVPI ADR
MONITORING CENTRE IN A
MEDICAL COLLEGE
1. Collection of ADR reports
2. Follow up to check completeness of
SOP
3. Data entry into VigiFlow
4. Reporting to PvPI NCC through
VigiFlow
5. Training/sensitization/feedback
through newsletters circulated by PvPI
NCC.

27. Causality Assessment
To determine the likelihood of a causal relationship between drug
exposure and adverse events it is necessary to evaluate
Association in time/place between drug use and event
Pharmacology (including current knowledge of the nature and
frequency of adverse reactions)
Medical or pharmacological plausibility (signs and symptoms, tests,
pathological findings, mechanism)
Likelihood or exclusion of other causes

28. Need to look at -
Product indication; duration of medication use
• Temporal relationship of ADR
– Appearance of ADR = “challenge”
– Disappearance of ADR = positive “dechallenge”
– Reappearance of ADR = positive “rechallenge”
• Previous exposure = “pre-challenge” (previous exposure to the suspect drug)
– Positive pre-challenge = ADR occurred in the past when the patient exposed to drug
– Negative pre-challenge = ADR did not occur in the past when the patient exposed to drug

29. WHO-UMC CAUSALITY CATEGORIES
Certain - Event or laboratory test abnormality, with plausible time relationship to drug intake Cannot be explained
by disease or other drugs. Response to withdrawal plausible (pharmacologically, pathologically)
Rechallenge satisfactory, if necessary.
Probable/Likely - - Event or laboratory test abnormality, with reasonable time relationship to drug intake
Unlikely to be attributed to disease or other drugs. Response to withdrawal is clinically reasonable. Rechallenge
not required
Possible – Event or laboratory test abnormality, with a reasonable time relationship to drug intake. Could also be
explained by disease or other drugs. Information on drug withdrawal may be lacking or unclear
Unlikely - Event or laboratory test abnormality, with a reasonable time relationship to drug intake that makes the
relationship improbable but not impossible. Disease or other drugs provide a plausible explanation
Conditional/Unclassified - More data for proper assessment needed, or Additional data under examination
Unassessible/Unclassifiable - Report suggesting an adverse reaction
Cannot be judged because information is insufficient or contradictory. Data cannot be supplemented or verified

30. What to Report
( WHO recommendations )
Every single problem related to the use of a drug, because probably nobody
else is collecting such information
All suspected adverse reactions
ADRs associated with radiology contrast media, vaccines, diagnostics, drugs
used in traditional medicine, herbal remedies, cosmetics, medical devices
and equipment
Lack of efficacy and suspected pharmaceutical defects
Counterfeit pharmaceuticals
Development of resistance

31. What to Report
Any drug suspecting of causing –
 Death
 Life-threatening event
 Hospitalization
Disability
Congenital Anomaly
 Requiring intervention to prevent permanent
impairment or damage

32. Special Cases for Pharmacovigilance
Some groups of medicinal products are not required to document their safety – natural
medicines, homeopathic preparations
Natural (herbal) medicines
Exact composition is often not known, efficacy nor safety is usually not documented
Marketing Authorization is granted on base of “traditional use”

33. LAW
Will reporting have any
negative consequences on the
health care professionals or
the patient?

34. LAW (contd.)
Submission of the ADR has no legal
implication on the reporter
Confidentiality of the reporter and the patient
will be maintained
The information is only for better
understanding of medicines used in India and
to safeguard the health of Indian population

37. A. Patient Information
1 Patient Initials -
2 Age at the time of Event or Date of Birth
3
Sex
Male Female Other
4 Weight (kg)

38. B. Suspected Adverse Reaction
5 Date of Reaction started (dd/mm/yyyy)
6 Date of recovery (dd/mm/yyyy)
7 Describe reaction or problem

39. C. Suspected Medication
8 Name (Brand and/or Generic)
Manufacturer (if known)
Batch No. /Lot No.
Exp. Date (if known)
Dose used
Route used
Frequency (OD, BD, etc)
Therapy dates
Date Started Date Stopped
Indication
Causality Assessment

40. C. Suspected Medication
9
Action Taken (Please tick)
Drug
Withdrawn
Dose
increased
Dose
reduced
Dose not
changed
Not
applicable Unknown
i
ii
iii
iv

41. C. Suspected Medication
10
Reaction reappeared after reintroduction
(please tick)
Yes No Effect unknown
Dose (if
reintroduced)
i
ii
iii
iv

42. C. Suspected Medication
11
Concomitant medical products
Including self-medication and herbal remedies with therapy dates
(Exclude those used to treat reaction)
Name
(Brand/
Generic)
Dose
used
Route
Used
Frequency
(OD, BD,
etc.)
Therapy dates
Indication
Date
Started
Date
Stopped
i
ii
iii
iv

43. 12 Relevant tests/laboratory data with dates
13
Relevant medical / medication history
(e.g. allergies, race, pregnancy, smoking,
alcohol use, hepatic/renal dysfunction
etc.)

44. 1
4
Seriousness of the reaction:
No If Yes (Please tick
anyone)
Death (dd/mm/yyyy)
Life threatening
Hospitalization (initial or prolonged)
Disability
Congenital anomaly
Required intervention to prevent permanent impairment /
damage
Other (specify)

45. 15 Outcomes
Recovered
Recovering
Not recovered
Fatal
Recovered with sequelae
Unknown

46. D. Reporter Details
16
Name and Professional Address Pin
Email
Tel. No. (with STD Code) Occupation
Signature
17 Date of this report (dd/mm/yyyy)

47. Mandatory Fields for Suspected ADR
Reporting Form
Patient initials
Age at onset of reaction
Date of onset of reaction
Reaction term(s)
Suspected medication
Reporter information
1
2
5
7
8
16, 17

48. Case studies
KEEP YOUR FORMS READY AND FILL IN THE DETAILS AS
SHOWN

49. Case - 1
Manisha Singh, a 65-year-old female patient admitted to the hospital on 12.01.2023 with chief
complaints of pain in the upper abdomen and nausea for the last 5 days. On physical examination,
she had yellowish discoloration of the palm, conjunctiva, and nail bed. Her weight was 65 kg. She had
a few episodes of psychotic attacks and was diagnosed with Schizophrenia, for which she was on Tab.
Largactil (Chlorpromazine)100 mg, 4 tablets at bedtime for the last 4 weeks. She was also taking Tab.
Diclofenac 50 mg twice-a-day (self-medication) for abdominal pain for three days before hospital
admission. She was investigated on the day of admission.
Laboratory parameters are as follows:
Alkaline Phosphatase = 180 U/L (Normal range: 25 – 100 U/L)
ALT = 205 U/L (Normal range: 10 – 40 Units/L)
Total Bilirubin = 5.0 mg/dL (Normal range: 0.8 – 1.2 mg/dL)
On admission, Chlorpromazine and Diclofenac therapy was stopped. Patient parameters showed
improvement and pain subsided.

50. Causality Assessment – ADR Case 1
Categories Time
sequence
Other drug
disease ruled
out
Dechallenge Rechallenge
Certain Yes Yes Yes Yes
Probable Yes Yes Yes No
Possible Yes No No No
Unlikely No No No No

51. Case - 2
Mr. Sushant Gupta, a 30-year-old male with 68 kg weight was diagnosed as a case of bacterial
meningitis. He was started empirically with Inj. Ceftriaxone 1 g IV BD and Inj. Vancomycin 500 mg IV QID
on 10.08.2023. The first dose of Inj. Ceftriaxone was given at 8 am and Inj. Vancomycin was given at 9 am
on 10.08.2023. After 10 minutes of the second drug administration, he started developing chills, rigors,
fever, urticaria, and intense flushing. He was treated with Inj. Pheniramine 25 mg IM, following which the
reaction completely subsided. Inj. Ceftriaxone was continued. However, the next doses of Inj.
Vancomycin scheduled on day 1 was not given. On day 2, the Inj Vancomycin was re-introduced at 9 am
to the patient. Similar symptoms developed again and quickly resolved after Inj. Pheniramine 25 mg IM.
Inj Vancomycin
– Brand Name: Vanzid
– Manufacturer: SWACH Healthcare
– Batch number: KKIL098
– Expiry date: Mar 2016
Inj Ceftriaxone
– Brand Name: Taximax
– Manufacturer: Wedley Labs
– Batch number: OPO659
– Expiry date: Dec 2016

52. Causality Assessment – ADR Case 2
Categories Time
sequence
Other drug
disease ruled
out
Dechallenge Rechallenge
Certain Yes Yes Yes Yes
Probable Yes Yes Yes No
Possible Yes No No No
Unlikely No No No No

53. References
•K.D. Tripathi. Adverse Drug Effects. Essentials of Medical pharmacology 8th edition. New Delhi (India); Jaypee brothers
publishers.2019. pg: 92-101.
•MvPI Toolkit - Indian Pharmacopoeia Commission (ipc.gov.in)
https://nhsrcindia.org/hc-technology/materiovigilance-programme-of-india
•Haemovigilance Programme Of India (HvPI) (nib.gov.in)
https://nib.gov.in/haemovigilance/HvPI_website/HvPI_index.html
•https://www.who-umc.org/global-pharmacovigilance/global-pharmacovigilance/50-years-of-pharmacovigilance/
•https://link.springer.com/article/10.1007/s11096-018-0657-1
•https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050268/
•https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838749/
•https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf
•https://www.who.int/teams/regulation-prequalification/regulation-and safety/pharmacovigilance/health-professionals-i
nfo/
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