PHARMACOVIGIALNCE AND PVPI INDIA, How to write Narrative ????

1. POST GRADUATION DIPLOMA IN
PHARMACOVIGILANCE CERTIFICATION
PROGRAM,
Dr . VENKATA RAMA RAO NALLANI
Associate Professor & HOD
Dept.of Pharmacy Practice,
Govt. General Hospital ,
Chalapathi Institute of Pharmaceutical
Sciences ,Guntur .
Mail id : nvramarao009@gmail.com id-
Contact No:+918331965697

51. ICSR
INDIVIDUAL CASE SAFETY REPORTING
Types of ICSRs
Valid ICSRs: If the report contains
Identifiable patient
Identifiable reporter
Suspect drug
Adverse event
2) Invalid ICSRs: If any of the above elements missed will be
invalid ISCR
Note: If any report without drug-event pair it will not be
considered as ICSR

52. . ICSRs based on source
1) Spontaneous reports:
Passive surveillance system: Health professionals are encouraged to
report adverse reactions which they believe to be drug-related directly to
the regulatory authority or
the company marketing the suspected product on a voluntary basis
2) Solicited reports: are those derived from organized data collection
systems, which include clinical trials, registries, post-approval named
patient use programs, other patient support and disease management
programs, surveys of patients or healthcare providers, or information
gathering on efficacy or patient compliance.

53. HOW THE INFORMATION REACHES????
• India – ‘Suspected Adverse Drug Reaction Reporting Form’
• UK – ‘Yellow Card’, since 1964
• Australia – ‘Blue Card’ , since 1964
• US – ‘Med Watch’ Form FDA 3500 – voluntary reporting
Form FDA 3500A - mandatory reporting

54. ADR REPORTING THROUGH DATABASE
VigiFlow is a web-based Individual Case Safety Report (ICSR)
management system that is specially designed for use by national
centers in the WHO Programme for International Drug Monitoring.
VigiFlow 5.1(Released on 14 June 2013)
Subscription for Vigiflow is free in India.
• Other tools:
ARISg (mainly used by Drug manufacturer in Europe)
Argus (mainly used by Drug manufacturer in USA)
Vigibase

55. CONTENT & STRUCTURE OF ICSR
• 4 critical pieces of information that must be included on the report :-
 Suspected drug(s)
 Suspect reaction(s)
 Patient details
 Reporter details

56. Suspected Drug(s)
• Name of medicine including brand and batch number
if known
• Route of administration, dosage form
• Daily dose
• Date medicine started and stopped if applicable
• Reason why the medication was given
• Multiple drugs can be listed if more than one drug is
suspected of causing the reaction…

57. Suspect reaction(s)
• Describe the reaction
• Include a diagnosis if relevant
• Include when the reaction occurred
• whether the reaction was considered to be serious and
complete tick box for reasons why
• Document if any treatment was given for the reaction
• Eventual outcome tick relevant box

58. Patient Details
• Sex of the patient
• Age at time of reaction
• Weight if known
• DOB
• Patients initials and local identification number (hospital or practice number)
which will identify patient to you in the event of future correspondence

59. Reporter details
• Must be completed in all cases
• Name and full address Need to acknowledge receipt of report and follow up
further information if necessary.
• Profession

60. • Other Details
Country of primary source
Regulatory clock start date/Day Zero
Report type
Medical history
Drug history included allergies and interactions
Other medication in the last three months including herbal and over the
counter meds.
De challenge/Re challenge

61. • Case Assessment
• Based on seriousness:
1) Serious cases
Seriousness criteria:
Hospitalization
Disability
life threatening
Death
Medically important
2) Non serious cases

62. Based on causal relationship:
Positive causality:
1) Probable
2) Possible
3) Very likely/Certain
Negative causality:
1) Doubtful
2) Not related
How to identify causality????????

63. TRENDS CRITERIA
• Temporal relationship
– is there a time relationship between event and drug?
• Rechallenge
– what happens when the patient is rechallenged with the drug?
• Exclusion
– have other factors been excluded, e.g., concomitant medications?
• Novelty
– has the reaction been described and reported before?
• Dechallenge
– did the reaction improve when the drug was withdrawn?
• Scientifically plausible
– is the event biologically/pharmacologically plausible?

64. TRENDS CRITERIA - CONTINUED
• Temporal Relationship – interval between start of drug and event onset:
• Acute onset – within minutes
Usually when given iv/sc etc; can also be after oral administration
Events eg. Anaphylaxis
• Subacute onset
Few hours to few days/few weeks
E.g. Infection, rash, headache, vomiting
• Chronic onset - weeks to few months
• E.g. hepatitis
• More likely to be serious rather than non-serious event
Delayed onset - months, years
E.g. malignancies, interstitial lung disease, liver failure, chronic renal failure

65. • Dechallenge – did the reaction improve when the drug was
withdrawn?
• If no treatment given, resolution after stopping the drug is perhaps
suggestive of an association.
• Rechallenge – what happens when the patient is re-challenged with
the drug?
Did the reaction reappear after restarting the drug?
This is suggestive of an association
Did the reaction not reappear after restarting of the drug?
This is inconclusive or perhaps suggestive of not an association

66. • Exclusion - Have other factors been excluded, e.g., co suspects,
concomitant medications or comorbidities?
•Presence of co-suspects
•Other comorbidities
•Temporal relationship of other confounders/events
•Reporter’s opinion
•Novelty - has the reaction been described and reported before?
•Scientifically plausible – is the event
biologically/pharmacologically plausible?

69. •Based on expectedness:
1)Expected events
2)Un expected events

70. •
How to write Narrative ????

71. ICSR TIMELINES
Sl. No Type of event Regulatory timeline
1 Initial fatal/life-threatening reports 7 calendar days
2
Other serious ICSRs, Non-serious
expeditable cases (watchlist etc)
15 calendar days
3 Pregnancy Exposure cases 15 calendar days
4
Follow-up information to initial
serious ICSRs, including fatal or
life-threatening ICSRs
15 calendar days
6
Initial and follow-up non-serious
ICSRs
Within required
timelines for
particular regulatory
authorities

72. COUNTRY-REGULATORY
AUTHORITY
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
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

73. PSUR
As per Schedule Y, PSUR includes all safety reports -
Spontaneous AE reports, PMS studies, Safety info from other
sources - published articles etc.
Subsequent to approval of the product, new drugs should be
closely monitored for their clinical safety once they are
marketed.
The applicants shall furnish Periodic Safety Update Reports
(PSURs) in order to - Report all the relevant new information
from appropriate sources;

74. PSUR
• Key role in safety assessment of Drugs.
• It involves compilation of safety data of drug over a
prolonged period of time.
• Provides broader view of safety profile of a drug.
• Worldwide, the most important aggregate report is the
Periodic Safety Update Report (PSUR)

75. PSUR SUBMISSION
First 2 yrs: every 6 month
Next 2 yrs: every year
After that every 3 years.
On the basis of PSURs: Regulatory
Authorities take the appropriate decision
for marketing of particular medicinal
product.

76. SPECIAL REPORTING SCENARIOS
Any information on patients with pregnancy
Babies on breast feeding
drugs used in the treatment of human
immunodeficiency virus (HIV)/Acquired
Immunodeficiency Syndrome (AIDS)
ADRs in children
Herbal products, including unlicensed remedies

77. REPORTS RELATED TO HERBAL
PRODUCTS
• Traditionally herbal products have been exempt from
licensing requirements by the conditions set out in Section
12 of the Medicines Act and for that reason there is a large
variety of unlicensed herbal preparations, including
traditional Chinese and Ayurvedic remedies, which are
increasingly available.
• In October 1996, the Yellow Card Scheme was extended to
include reporting for unlicensed herbal remedies

78. • Kava-kava (Piper methysticum): produced serious
hepatotoxicity, the CSM prohibited the use of Kava-kava in
unlicensed medicinal products in July 2002 and this was
followed by a prohibition order in January 2003.
• In January 2002, the European Commission adopted
formal proposals for a Directive on Traditional Herbal
Medicinal Products.
• This new Directive requires that all medicinal herbal
products will be required to be registered under the
Traditional Herbal Medicines Registration Scheme (THMRS)

79. PHARMACOVIGILANCE ACHIEVEMENTS IN
INDIA
• Serodiagnostic test kits for diagnosis of
tuberculosis (with effect from 7Jun2013).
• Dextropropoxyphene (with effect from 23May2013)
.
• Fixed dose combination of Flupentixol+Melitracen
(with effect from 18Jun2013).
• Analgin (with effect from 18Jun2013)
• Pioglitazone (with effect from 18Jun2013)

81. WE LEARN FROM FAILURE, NOT FOR SUCCESS ! !
I HOPE I HAVE JUSTIFIED YOUR TIME !!!!!!!
Thank you