6. Pre-Clinical Phase Data Generation
◎ Exploratory toxicology:
Provide a rough quantitative estimate of
toxicity (acute or repeated dose)
Provides main organs and systems
involved
7. Pre-Clinical Phase Data Generation
◎ Regulatory toxicology:
Performed to GLP standards and
comprise regulatory requirement by
authorities
Performed to support an application
for marketing approval
8. Pre-Clinical Phase Data Generation
◎ Exploratory toxicology: In-vitro and in-
vivo studies:
Mutagenicity
Cytotoxicity
Immunotoxicity
Hepatotoxicity
Embryotoxicity
10. Pre-Clinical Phase Data Generation
Safety pharmacology:
Pharmacological testing to check that the
drug does not produce any obviously
hazardous acute effects known as safety
pharmacology.
11. Pre-Clinical Phase Data Generation
Safety pharmacology:
System wise tests
Follow up tests
Supplementary tests
12. Pre-Clinical Phase Data Generation
Safety pharmacology:
System wise tests
• CVS: BP, Heart rate, ECG changes
• Respiratory: RR, Tidal volume
• CNS: Behavioural Changes, motor
activity, Body temperature
14. Pre-Clinical Phase Data Generation
Safety pharmacology:
Supplementary tests:
• Renal function: Urinary volume, pH,
proteinuria, blood urea
• GIT: gastric secretion, pH, GI motility, GI
transit time
15. Pre-Clinical Phase Data Generation
Acute toxicity:
o28 days repeat dose toxicity and
recovery in 2 species
Chronic toxicity:
o3-12 months chronic toxicity in 2
species
16. Pre-Clinical Phase Data Generation
Reproductive toxicity:
oReproductive toxicity in 1 species
Carcinogenicity:
o24 months carcinogenicity in 2 species
18. Clinical Trial Safety Data Generation
• 20–100 People
• Usually 1-2 Years
Phase I (Safety)
• 100-300 People
• 1-2 Years
Phase II (Efficacy
and Safety)
• 1000-3000 Peoples
• 2-3 Years
Phase III
(Efficacy and
Safety)
19. Clinical Trial Safety Data Generation
Serious adverse events reporting
Conducting Subjects follow up
Ensuring subject compliance
Continue communication
20. Clinical Trial Safety Data Generation
Adverse
Events
Unexpected
adverse
events
Any
laboratory
abnormalities
Serious
Adverse
events
Adverse
events of
special
interest
Adverse drug
reactions
21. 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
22. Clinical Trial Safety Data Generation
Sources:
Clinical Information sources
Non Clinical Information Sources
23. 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
24. Clinical Trial Safety Data Generation
Sources:
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)
25. 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
26. 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
28. 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)
29. Post Marketing Safety Data Generation
PMS
Spontaneous
reporting
Prescription
Event
Monitoring
Electronic
health records
Observational
studies
Registries
30. 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
31. 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