Due to side effects of Medicines and Medical Devices increasing day by day it is important to monitor the Adverse Events arising out of use of Medicines and Medical Devices. The Pharmacovigilance and Materiovigilance monitors adverse events arising our of usage of Drugs and Medical Devices respectively. This chapter also deals with Drugs and Cosmetics Act 1940 and their important provisions.

1. P H A R M A C O V I G I L A N C E ,
M A T E R I O V I G I L A N C E ,
D R U G S A N D C O S M E T I C
A C T , C D S C O
D A Y - 4 - I I H M R - B Y D R . S . B . S I N H A -
M E D I C A L D E V I C E R E G U L A T O R Y
C O N S U L T A N T

2. I N T R O D U C T I O N
Pharmacovigilance is a system of monitoring Safety and
Effectiveness of Drugs and other Pharmaceuticals. Similarly
Materiovigilance is a a system of Monitoring Safety and
Effectiveness of a Medical Device.
WHO Definition- Pharmacovigilance is the science and activities
relating to the detection, assessment, understanding and
prevention of adverse effects or any other medicine/vaccine
related problem.
PvPI- Pharmacovigilance Program of India was Launched in 2010
MvPI- Materiovigilance Program of India was Launched in 2015
Both have their National Coordination Centres at Indian
Pharmacopoeia Commission Located at Ghaziabad

3. W H Y
P H A R M A C O V I G I L A N C
E
• Dying from a disease is Unfortunate but dying from Adverse
Drug Reaction is not acceptable.
• Estimated death because of ADR is 5700 per annum in UK.
• ADR. were the 4th-6th most common cause of eaths in USA
in 1994
• Humanitarian concerns- ADR are expensive- Insufficient of
safety from Clinical Trials and Animal Experiments as they
are done only in very small population. 6.5% of hospital
admissions are because of ADR. Seven 800 beds hospitals
are occupied in UK with all ADR Cases. Cost 446 million
pounds per annum in UK. Many drugs have been recalled
because of ADR after successful CT.

4. S C O P E A N D O B J E C T I V E S
To create nationwide
system for patient
safety and adverse
event reporting.
To identify and
analyze new signals
from the reported
cases.
To analyze Benefit-
Risk ration of the
Medications and MD.
To support regulatory
agencies in decision
making process on
safe usage of
Medications and MD
To communicate the
safety information to
all the stakeholders
to minimize the risk.
Training and
Consultancy support
to other Agencies
across the globe.
To promote rational
use of Medicines and
MD

5. S H O R T
T E R M
G O A L S
To develop and implement Pharmacovigilance
system in India.
To enroll all MCI Recognised Medical Colleges
in India in East, West, North and South.
To encourage healthcare professionals in
reporting of Adverse Drug Reactions, vaccines,
Medical Devices and Biological products.
Collection of Case Reports and Data.

6. L O N G T E R M
G O A L S
To expand PvPI and MvPI to all
hospitals.
To develop and implement e-
reporting system in India.
To develop reporting culture in
all HCP..
To make ADR Reporting
mandatory in India

7. C O M M I T T E E S U N D E R N C C
• Steering Committee
• Working Group.
• Quality Review Panel.
• Signal Review Panel.
• Core training Panel

8. P V P I
G O V E R N A N C E
S T R U C T U R E

9. M V P I -
G O V E R N A N C E
S T R U C T U R E

11. C D S C O - C E N T R A L D R U G S A N D
S TA N D A R D S O R G A N I Z AT I O N
• CDSCO is the main regulatory body for regulating MD, Pharmaceuticals and Clinical
Trials.
• HO is located in New Delhi and works under DGHS under MoHFW.
• It is headed by DGCI appointed by MoHFW.
• Is assisted by DTAB (Drug Technical Advisory Board) AND DCC (Drugs Controller
Committee)

13. O F F I C E S
• Zonal offices at Mumbai, Kolkata, Chennai, Ghaziabad, Ahmedabad and Hyderabad.
These are involved in GMP Audits and Inspection of Manufacturing Units of large volume
parentals Large Volume Parentals are single dose injectiosn for administrating through IV
Route), sera (a liquid that is taken from the blood of an animal and given to people to
protect them from disease, poison, etc.), vaccines and blood products.
• Sub Zonal Offices- Chandigarh, Jammu and Bangalore. These offices coordinate with
State Drug Control Authorities under their jurisdiction for uniform standard of Inspection
and enforcement.
• CDTL- Kolkata, Mumbai, Chennai, Kasauli, Guwahati and Chandigarh- Responsible of
Quality Control of Drugs and Cosmetics in the Country.

14. T E A B R E A K 1 1 . 1 5 A M
W E W I L L M E E T A T 1 1 . 3 0 A M

19. R O L E O F
C D S C O
CDSCO HQ is responsible for :
Taking appropriate regulatory decision and action
regarding Drug and MD Safety. Actions include
Recall of Medical Devices, Recall of Marketing
Permission etc.
Propagating MD and Drug Safety related decisions
to stakeholders.
Provide administrative and Technical Support to run
PvPI and MvPI.

20. T E R M I N O L O G I E
S
ADR- Adverse Drug Reaction- An adverse reaction of a normal
dose of Drug. For MD it is MDAE-Medical Devices Adverse
Event
AE-Adverse Event- A negative unexpected experience during
a clinical trail that may or may not be associated with Drug. AE
caused because of Drug it is ADR and when associated with a
MD it is MDAE
SAE-Serious Adverse Event-An adverse event that is fatal,
results in hospitalization or disability.
SIGNAL- New, previously unknown safety information. As per
WHO it is the Reported information on a possible Causal
association between and AE and a Drug, the relationship being
unclear or incompletely documented previously.

21. P H A R M A C O V I G I L A N C E P R O C E S S
• Detecting and reporting an ADR/MDAE-
• ADR Form is filled with Patient and AE Details, and this is later entered into the
database.
• The reporting can be Spontaneous (voluntary) in which the HCP fill up the form and
report the same to their National Pharmacovigilance Centers OR to the manufacturers.
• Mandatory reporting has to be done by Manufacturers in the form of PSUR (Periodic
Safety Update Reports). A regulatory document is prepared by the Marketing
Authorization Holder and submitted to regulatory. It includes scientific evaluation of the
Risk Benefit balance. Submission frequency of PSUR is every 6 months for the first 2
years, Every year for next two years, after that every three years.
• Data collection and Capture, Data Storage & Maintenance, Data Selection,
Retrieval and Manipulation.

22. L U N C H B R E A K 1 . 0 0 P M
W E W I L L M E E T A T 2 . 0 0 P M

27. R E P O R T I N G
What to report- ADR/MDAE
Who can report- All HCP
Where to report- To nearest Adverse Drug Reaction Monitoring Center (AMC)
OR to the NCC (National Coordination Center) directly. Can also be emailed to
pvpi@ipcindia.net
What happens to the Submitted Report- Causality Assessment is carried out by
AMC by using WHO-UMC Scale. The Analyzed Forms are forwarded to NCC
through ADR Database. Finally the data is analyzed and forwarded to Global
Database managed by WHO Uppsala Monitoring Center in Sweden.
The reports are periodically Reviewed by the NCC-PvPI to continuously assess
the Risk Benefit ratio, It is submitted to Steering Committee constituted by
MoHFW

28. C A U S A L I T Y
A S S E S S M E N T
? ?
Is the assessment of relationship between the Drug Treatment/MD
Usage to the AE.
Used to evaluate and check whether the Drug Treatment/MD
Usage is responsible for the occurrence of the AE.
It is an essential part of the ADR Report and is an important task
done by all the Pharmacovigilance Agencies in each country.
OBJECTIVES-
Provide relationship between Drug/MD and the AE.
Signal Detection
Plays an essential part in evaluating ADR Reports in early warning
systems and for regulatory purposes

29. M E T H O D S
O F
C A U S A L I T Y
A S S E S S M E N
T
Expert Judgment and Global Introspection.- Expert or a group of expert
give their opinion based on their knowledge, experience and available
data. WHO UMC Causality Assessment Criteria is most commonly used
method.
Algorithm based- Based on problem specific flow charts and structured
questions. Naranjo Scale is the most common Algorithm for Causality
Assessment.
Probabilistic methods- Study of Prior Probability (Calculated from
epidemiological information) and Posterior Probability (Combines the
epidemiological information with the evidence in the individual case)
ACCA-Advisory Committee on Causality Assessment-Canadian
Assessment System for VACCINES as Vaccines are provided in very
large number of healthy persons hence must be very safe and it consists
of Experts in Pediatrics, Epidemiology, Infectious Disease, Immunology,
Neurology, Pathology, Adverse Event Surveillance and Microbiology.

30. W H O U M C
C R I T E R I A
Assessment is based on four Criteria
(a) Time relationship between Drug use and AE
(b) Absence of other competing Criteria (medications and Disease
process itself)
( c) Response to Drug withdrawal OR Dose reduction ( de-challenge)
(d) Response to Drug readministration (re-challenge)
RESPONSE is grouped into FOUR Causal Assessment based on meeting
the Criteria
CERTAIN- When all FOUR Criteria are met
PROBABLE-When a, b and c are met.
POSSIBLE- When only a is met.
UNLIKELY- When a and b are not met.

31. W H O U M C
C R I T E R I A
Based on the FOUR Criteria the RESPONSE is also Categorised
into the following:
Unclassified/Conditional- When more data is required and is being
sought
Unclassifiable/Unassessable- When the data is contradictory and
can’t be assessed.
CONCLUSION
CERTAIN- Implies the AE is related to Drug
PROBABLE- Implies AE is most probably related to DRUG and
other causes are unlikely.
POSSIBLE- Other causes are possible for AE
UNLIKELY- AE not related to DRUG. It is likely because of other
causes.
UNASSESSABLE- Can’t assess because of incomplete or
contradictory information.

32. E X A M P L E S
W H O U M C
CERTAIN- Dizziness starts after 30 minutes of taking of
antihypertension Drug and no other Drugs are taken. AE Stops
on Stopping the Drug (positive De challenge) and starts again
after taking the Drug (positive re challenge) [All four Criteria
met]
PROBABLY- Diarrhea after taking Ampicillin.[Only a ,b and
care met]
POSSIBLY- Abnormal Liver Function Tests after taking
histamine.[Only Criteria a is met]
UNLIKELY- Heart attack 3 weeks after taking a drug that has
terminal half life of 10 min.[Criteria a and b not met]

33. T E A B R E A K 3 . 1 5 P M
W E W I L L M E E T A T 3 . 3 0 P M

35. A D R
R E P O R T I N G
T H R O U G H
V I G I F L O W
VigiFlow is web based ICSR (Individual Case
Safety Reporting) System that is specifically
designed for use by National Centers in the WHO
Program for International Drug Monitoring.
Subscription for VogiFlow is free in India.
Other tools are ARISg mainly used by Drug
Manufacturers in Europe , Argus mainly used by
Drug Manufacturers in USA and Vigibase,

37. D R U G S A N D
C O S M E T I C
A C T
Objective- To regulate import, manufacture, Storage and
sales of Drugs and cosmetics for safe and effective usage
by Qualified personnel only.
Act Passed in 1940
Drugs and Cosmetic Rules were passed in 1945
Since 1940 Several Amendments have been passed.
Drug is defined as a substance, diagnostics and Medical
Devices.
Cosmetics is defined as any product applied to human body
for beautification and cleaning.

38. C H A P T E R S -

39. I M P O R T A N T
S C H E D U E S
T O
T H E R U L E S

40. I M P O R T A N T
S C H E D U L E S
T O T H E
R U L E S

41. S C H E D U L E -
M

42. A D M I N I S T R AT I O N O F T H E A C T &
R U L E S
• Advisory- To Advise Central and state Govt on Policy matters to maintain uniformity.
• DTAB (Drug Technology Advisory Board)- Is main body to recommend policy matters.
• DCC- Dugs Consultative Committee- Advisory to DTAB
• Analytical- CDL- Central Drug Lab, Drug Control Labs in State . The labs test the food
and srug samples. There are Govt. Analysts who analyze the samples sent by the
Inspectors
• Executives- LA- Licensing Authorities- Recommend Licensing, Inspect the facility and
Investigate a complaint.
• Controlling Authorities- Drug Inspectors are appointed under Sec 21 will inspect the
facilities and take samples for analysis.

43. A D U L T E R A T E D A N D
S P U R I O U S D R U G S

46. Q U E S T I O N S
• THANK YOU