This document outlines safety reporting procedures for a clinical trial, including definitions of adverse events and serious adverse events, causality assessment guidelines, reporting timelines, and medical management of adverse events. Adverse events will be monitored for 28 days following vaccination and reported within required timelines. Serious adverse events must be reported within 24 hours of occurrence and followed up until resolution. The ethics committee, regulatory authorities, and sponsor will assess causality and determine compensation if needed.

1. Presentation For:
Safety Reporting
Protocol: PBL/CR/2013/02/CT/ESIX

2. Contents
Definitions
Solicited Reactions
Causality Assessment
AE Reporting Timelines

3. Definitions

4. Adverse Event
Definition: Any untoward medical occurrence
in the subject administered a pharmaceutical
product
• Causal relationship not necessary
• Can be any unfavorable sign (including an
abnormal laboratory finding, for example).
• Can be inter-current illnesses or injuries
• Can be exacerbation of pre-existing
conditions.

5. Serious Adverse Event
Any AE that:
Results in the death of the subject
Is life-threatening
Requires inpatient hospitalization or
prolongation of existing hospitalization
Results in persistent or significant disability or
incapacity
Results in Congenital anomaly
Other Important medical events (Which as
per PI opinion can be considered serious)

6. Grading of Adverse Events
• Mild(Grade I): Usually transient in
nature and generally not
interfering with normal activities
• Moderate(Grade II): Sufficiently
discomforting to interfere with
normal activities
• Severe(Grade III): Prevents
normal activities

7. Solicited Reactions

8. Solicited Local Reactions
None Mild (Grade 1) Moderate
(Grade 2)
Severe (Grade 3)
Pain None Minor reaction to touch Cries/protests on
touch
Cries when limb is
moved/
spontaneously
painful
Redness
*
<2.5
cm
2.5- 5 cm 5.1 to 10 cm > 10 cm
Swelling
*
<2.5
cm
2.5- 5 cm 5.1 to 10 cm > 10 cm
* based on the largest diameter

9. Solicited Systemic Reactions
None Grade 1 Grade 2 Grade 3
Fever
(Axillary)
< 38°C 38.0-38.4°C > 38.5-38.9°C > 39.0°C
Acute
allergic
reaction
None Localized urticaria
(wheals) with no
medical intervention
Localized urticaria with
medical intervention
OR Mild angioedema
with no medical
intervention
Generalized urticaria
OR Angioedema with
medical intervention OR
Symptomatic mild
bronchospasm
Excess
Sleepiness/
Drowsiness
Behavio
r as
usual
Drowsiness easily
tolerated
Drowsiness that
interferes with normal
activity
Drowsiness that
prevents normal activity

10. Solicited Systemic Reactions
None Grade 1 Grade 2 Grade 3
Irritability/
restlessne
ss/
fussiness
Behavior
as usual
Crying more than
usual/ no effect on
normal activity
Crying more than
usual/ interferes
with normal
activity
persistent crying and the
child could not be
comforted
/ prevents normal activity
Poor
eating
Appetite
as usual
Eating less than
usual/ no effect on
normal activity
Eating less than
usual/ interferes
with normal
activity
Not eating at all

11. Solicited Systemic Reactions
None Grade 1 Grade 2 Grade 3
Vomiting None Occasional but able to
eat/drink
normal amounts
Repeated with limited
oral intake
Continuous, unable to
keep down liquids or
solids
Diarrhea None Transient or
intermittent episodes
of unformed stools OR
Increase of ≤ 3 stools
over baseline
per 24-hour period
Persistent episodes of
unformed to watery
stools OR Increase of
4 – 6 stools over
baseline per 24-hour
period
Bloody diarrhea OR
Increase of ≥ 7 stools
per 24-hour period OR
IV fluid replacement
indicated

12. Causality Assessment

13. Causality Assessment (WHO Guidelines)
1. Case with adequate information for causality
conclusion
A. Consistent causal association to immunization
A1. Vaccine product-related reaction
A2. Vaccine quality defect-related reaction
A3. Immunization error-related reaction
A4. Immunization anxiety-related reaction

14. B. Indeterminate
B1. Temporal relationship is consistent but insufficient
definitive evidence that vaccine caused the event (it may
be a new vaccine-linked event). This is a potential signal.
B2. Conflicting trends of consistency and inconsistency (i.e. it
may be vaccine-associated as well as coincidental and it
is
not possible clearly to favour one or the other).
Causality Assessment (WHO Guidelines)

15. Causality Assessment (WHO Guidelines)
1. Case with adequate information
A. Consistent causal association to immunization
B. Indeterminate
C. Inconsistent causal association to immunization
(coincidental)
2. Case without adequate information

16. C. Inconsistent causal association (coincidental):
Due to underlying condition or conditions caused by
exposure to something other than vaccine.
2. Case without adequate information (Unclassifiable)
• Requires additional information for causality assessment.
Case should be classified if information is available.
Causality Assessment (WHO Guidelines)

17. AE Reporting Timelines

18. Solicited/Local and Systemic Reactions:
• Will be recorded up to 30 minutes on the day of each
vaccination and for 7 days post-vaccination.
• Will be noted in subject diary card by the parent and copied
on to relevant section of the CRF pages by the Investigator
at subsequent visit.
Unsolicited Adverse Reactions
• Will be recorded in the ‘Adverse Event’ pages in the CRF
for 28 days after vaccination.
AE will be followed up till the satisfactory resolution or
stabilization
AE Reporting

19. SAE Reporting
Initial Report:
– As soon as it happens
– Must contain:
• An identifiable patient
• An identifiable reporter (Investigator)
• A suspect drug/ biological product
• Description of event (max information available)

20. SAE Reporting
All SAE
Investigator with in
24 Hrs occurrence
DCGI Sponsor Ethic Committee
DCGI: dci@nb.nic.in. / dci@cdsco.nic.in. Fax: 91-11-23236973 / Courier:
DCGI, DGHS, CDSCO, FDA Bhawan, Kotla Road, New Delhi – 110002
Sponsor: PVG@panaceabiotec.com; atulgupta@panaceabiotec.com
PVG no: +91-9650138282, 9717287654 Fax No.: +91-11-41578085

21. SAE reporting
Analyzed Report of SAE
By Sponsor & Investigator
Separately
EC Head of institute DCGI
With in 10 days of
occurrence
Also to DCGI Expert Committee in case of Death

22. SAE reporting
Assessment of SAE by
Ethics Committee
DCGI
With in 21
calendar days
Also to DCGI Expert Committee in case of Death

23. SAE Reporting
DCGI Determine cause of SAE and Quantum of
compensation and pass order to Sponsor
within 3 months of receipt of report of SAE
from EC
Sponsor to pay within 30 days of receipt
of order
Submits details of compensation
paid to DCGI

24. Medical Management of AE
• Medical Management: Free medical management as long
as it is required or till such time it is established that the
injury is not related to the clinical trial, whichever is earlier.
• Compensation: In case the injury is related to the Clinical
trial, such subject shall also be entitled for financial
compensation (over and above medical management). In
case there is no permanent injury, the quantum of
compensation shall commensurate with the nature of the
non-permanent injury, loss of wages and transportation.