Safety data generation in Pharmacovigilance, B. Pharmacy, SEM-8( Unit-IV).

1. SAFETY-DATA-
GENERATION
By: Saroja P. Adepawar
SUB: Pharmacovigilance
UNIT: IV
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2. SAFETY-DATA-GENERATION
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3. SAFETY-DATA-GENERATION
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4. PRE-CLINICAL PHASE
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5. Pre-Clinical
Phase Data
Generation
Exploratory
toxicology
-Provide a rough
quantitative estimate of
toxicity (acute or repeated
dose)
-Provides main organs and
systems involved
In-vitro and in- vivo
studies
Mutagenicity
Cytotoxicity
Immunotoxicity
Hepatotoxicity
Embryotoxicity
Regulatory
toxicology
-Performed to GLP
standards and
comprise regulatory
requirement by
authorities
-Performed to support an
application for marketing
approval
Safety pharmacology
GLP guidelines
Acute toxicity
Chronic toxicity
Reproductive toxicity
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6. PRE-CLINICAL PHASE DATA
GENERATION
System wise
tests
CVS: BP, Heart rate, ECG changes
Respiratory: RR, Tidal volume
CNS: Behavioural Changes, motor
activity, Body temperature
Follow up
tests
CVS: Cardiac output, ventricular
contractility
Respiratory: pulmonary arterial
pressure, blood gases
Supplementa
ry tests
Renal function: Urinary volume,
pH, proteinuria, blood urea
GIT: gastric secretion, pH, GI
motility, GI transit time
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7. PRE-CLINICAL PHASE DATA
GENERATION
Acute toxicity: 28 days repeat dose toxicity and recovery in 2 species
Chronic toxicity: 3-12 months chronic toxicity in 2 species
Reproductive toxicity: Reproductive toxicity in 1 species
Carcinogenicity: 24 months carcinogenicity in 2 species
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8. CLINICAL TRIAL SAFETY DATA
GENERATION
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9. SAFETY-DATA-GENERATION
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10. CLINICAL TRIAL SAFETY DATA
GENERATION
Serious adverse events reporting
Conducting Subjects follow up
Ensuring subject compliance
Continue communication
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11. CLINICAL TRIAL SAFETY DATA
GENERATION
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12. CLINICAL TRIAL SAFETY DATA
GENERATION
Adverse Event: Any untoward medical occurrence observed during
treatment while a pharmaceutical product which does not necessarily
have a causal relationship with the treatment.
• Adverse outcomes after use of the drug
• Any new clinical experience may or may not be linked to the use of
drug
• Eg: any laboratory abnormality or new symptoms after the use of
the drug
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13. CLINICAL TRIAL SAFETY DATA
GENERATION
Sources:
Clinical Information sources:
Data from clinical and epidemiological studies
Data from pharmaceutical companies
Safety profile of the drugs of similar class or type
Data from clinical studies
Non Clinical Information Sources
Chemical structure, class indication, adverse effects, actions
In-vitro studies report
Data from toxicology studies in animals (Cardiotoxicity, hepatotoxicity, renal
toxicity, carcinogenicity, mutagenicity)
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14. CLINICAL TRIAL SAFETY DATA
GENERATION
Serious adverse event
Adverse drug reaction
Unexpected adverse event: Nature and severity of which is not
consistent with the risk information described in general
investigational plan of investigator’s brochure
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15. CLINICAL TRIAL SAFETY DATA
GENERATION
Reporting timelines:
Any Serious, unexpected or life threatening adverse events must be reported within 7
days
Any other unexpected AEs that are neither fatal not life threatening should be
reported within 15 days
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16. POST MARKETING SAFETY DATA
GENERATION
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17. POST MARKETING SAFETY DATA
GENERATION
Periodic safety update reports
PSUR Process
Intake of ADR information
Data Retrieval
Data analysis
PSURs should be submitted every months for first two years and
annually for subsequent 2 years. (India)
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18. POST MARKETING SAFETY DATA
GENERATION
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19. POST MARKETING SAFETY DATA
GENERATION
Post marketing safety evaluation data source:
Product’s preapproval safety profile
Current FDA approved label
FDA adverse event reports (FAERS)
Reports of vaccine adverse event reporting system (VAERS)
Periodic submission of safety reports
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20. POST MARKETING SAFETY DATA
GENERATION
Post marketing reports timeline:
Serious and unexpected AEs: FDA recommends report to be submitted
within 15 days
Follow up - Up to 15 days alert reports should be submitted within 15
days
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21. THANK YOU
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