REGULATORY AFFAIRS FIRST SEMESTER M.PHARM

1. ROLE OF PHARMACOVIGILANCE IN
CLINICAL TRIALS
PRESENTED BY :
AKHILAA
1st YEAR M PHARM
PHARMACEUTICS
NGSMIPS

2. CONTENTS
 INTRODUCTION
 PHARMACOVIGILANCE IN CLINICAL TRIALS
 STAKEHOLDERS IN CLINICAL TRIAL SAFETY
 EXPEDITED ADR REPORTING IN EU, INDIA, US
 PHARMACOVIGILANCE PROGRAM IN INDIA
 CONCLUSION
 REFERENCES

3. INTRODUCTION
PHARMACOVIGILANCE:
 Known as Drug safety.
 According to WHO, Pharmacovigilance is defined as “the pharmacological
science and activities relating to the detection, assessment, understanding and
prevention of adverse effects or any other drug-related problem”.
 Removes of approved and licensed products from the market because of clinical
toxicity, which is caused by adverse drug reactions in the body.
 Aims :
o To improve patient care and safety.
o To contribute to assessment of benefit, harm and effectiveness of medicine.
o To promote rational and safe use of medicine.

4. CLINICAL TRIALS:
 Clinical trials are research studies which describes process of new medical
approaches and their actions in public.
These are the experiments or observations done in clinical research.
 Aims:
• To evaluate the safety and efficacy of experimental drug relative to its adverse
drug reactions.
• To license the process of new drug.
 Advantages of conducting Clinical trials in India:
Ongoing support and cooperation from the government, Lower cost, Availability of
good infrastructure.

5. DRUG SAFETY MONITORING:
 Randomized clinical trials need to be monitored.
 Data and safety monitoring : Process for reviewing accumulated outcome data
from an ongoing clinical study to ensure safety , validity and scientific merit of the
study.
 Medical monitoring is increasing every year.
 These can be performed by a licensed physician with experience in clinical
development and those who are capable of reviewing adverse events.
 Need to be responsible for identifying safety signals and responsible for data
analysing which influence the medical outcome.
 They track patients safety throughout the trial.

6. PHARMACOVIGILANCE IN CLINICAL TRIALS
Pharmacovigilance begins with clinical trials that provides data on the benefits and
risks of a drug.
Pharmacovigilance analysis conducted in Phase I, Phase II, and Phase III clinical
trials gives drug companies data on the drug’s safety profile.

7. Key stakeholders in clinical trial safety:
Ensuring safety in clinical trials is a shared responsibility across the following key
stakeholders.
1. Clinical Trial Subject
2. Investigator
3. Clinical Trial Sponsor
4. Safety Monitoring Boards
5. Ethics Committee
6. Regulatory Agency

8. Clinical Trial Subject A clinical trial subject is an individual who participates in a clinical trial,
either as a recipient of the investigational and products or as a control.
Investigator An investigator is a person responsible for the conduct of a clinical trial, at a
trial site. If a trial is conducted by a team of individuals at right side, the
investigator is responsible leader of the team and may be called the principal
investigator.
Clinical trial sponsor An individual, company, institution or organisation which takes responsibility
for the initiation, management and for financing of a clinical trial.
Independent data
monitoring committee
It is a committee that may be established by the sponsor to assess at intervals
of the programs of clinical trials, the safety data, and the critical efficacy
endpoints, and to recommend to the sponsor whether to continue, modify, or
stop a trial.

9. Ethics Committees (EC) /
Institutional Review Board
(IRB)
An independent body (a review board or a committee, institutional,
regional, national), constituted of medical professionals and non-
medical member, whose responsibility is to ensure the protection,
safety, and well-being of human subjects involved in a trial and to
provide protection among other things, reviewing and approving /
providing favourable opinion on trial protocol.
Regulatory agencies Regulatory agencies are bodies having power to regulate. As per ICH
GCP guidelines, regulatory authority review submitted clinical data
and conduct inspections. They are also referred to as competent
authorities.

10. EXPEDITED REPORTING IN THE EUROPEAN UNION,
INDIAAND THE UNITED STATES
Expedited reporting is accelerated reporting of certain types of adverse drug
reactions (ADRs) that may have a greater impact on safety and hence, may require
rapid reporting and subsequent analysis.
Typically, expedited reporting refers to cases of ADRs that are both serious and
unexpected.
Adverse Drug Reaction (ADR):
Defined as all noxious and unintended response to the medicinal products related to
any dose.
Adverse reactions are a subset of all suspected adverse reaction when there is reason
to conclude that the drug caused the event.

11. Classification of ADR:
i. Mild
Drug can be continued without any treatment.
e.g., Occurrence of drowsiness while on therapy with anti-allergic medications.
ii. Moderate
Drug was changed or stopped; reaction require treatment
e.g., Occurrence of hypokalaemia while on diuretic therapy.
iii. Severe
These may be life-threatening and requires a discontinuation of the drug therapy.
e.g., Occurrence of QT prolongation or drug-induced liver failure

12. Serious Adverse Events (Experience) or Serious Adverse Reaction (SAR):
An SAE or SAR is any untoward medical occurrence that at any dose:
i. Results in death
ii. Is considered life-threatening.
iii. Requires inpatient hospitalization or prolongation of existing hospitalization.
iv. Results in persistent or significant disability/ incapacity
v. Is a congenital anomaly/ birth defect.

13. Unexpected Adverse Drug Reaction:
An adverse reaction, the nature or severity of which is not consistent with the
applicable product information.
In other words, it is considered unaffected if it is not listed in the investigators
brochure or is not listed at the specificity or severity that has been observed.
Suspected Unexpected Serious Adverse Drug Reaction (SUSAR):
 An adverse event that is serious, possible casually related to a medicinal product
and is considered unexpected as per the investigator’s brochure.
A SUSAR requires expedited reported to most of the regulatory agencies.

14. Reporting Process for Expedited Reporting Of Serious Adverse Event
(Experience) (SAE) or Serious Adverse Reaction (SAR):
These reporting process starts from the awareness of the occurrence of the serious
adverse events at the clinical trial site. The investigator has to report SAR (usually
within 24 hours) to the sponsor.
The sponsor, depending on the regulations, may have to report the same to the
concerned regulatory agencies
SAR may also have to be reported to the ethics Committee (IRB) by either the
sponsor or by the investigator depicts the sponsor or by the investigator depicts the
reporting process for an SAR.

15. Usually there are two types of expedited clinical trials:
i. 15 days reports where the sponsor has to report SUSARs to the regulatory agency
to the ethics committee within 15 calendar days of the information reaching the
sponsor.
ii. 7 days reports that are subsets of the 15-day report, where in the sponsor has to
report fatal or life-threatening SUSARs to the regulatory agency and to the ethics
committee 7 calendar days of the information reaching the sponsor.

16. EUROPEAN UNION
 Responsibility of the investigator:
 The investigator should report all serious adverse events immediately to the
sponsor except for those that the protocol or investigator brochure identifies as
not requiring immediate reporting.
 The immediate reports shall be followed by detailed, written reports.
 The timeline of immediate reporting should allow the sponsor to take the
appropriate measures to address potential new risks in clinical trial.
 Therefore, the immediate report should be made within a very short period of
time and should not exceed 24 hours following the knowledge of the serious
adverse event.

17.  Responsibility of the sponsor
 The sponsor should report all suspected, unexpected, Serious Adverse Drug
Reactions (SUSAR) that are fatal or life-threatening as soon as possible to the
competent authorities and to the ethics committee and in any case no later than 7
calendar days
 Relevant follow-up information should be subsequently communicated within an
additional 8 days.
 The other SUSAR should be reported to the competent authorities and to ethics
committee as soon as possible but within the maximum of 15 days of the first
knowledge by the sponsor.
 The sponsor also has the responsibility to inform all the investigators in the
clinical trials about SUSARs.

18. INDIA
 Responsibility of the investigator
 Investigator shall report all serious and unexpected adverse events to the sponsor
within 24 hours and to the ethics committee that accorded approval to the study
protocol within 7 working days of their occurrence.
 The report of the serious adverse events, after due analysis shall be forwarded by
the investigator to the license authorities , chairman of the ethics committee and
the head of the institution where the trial has been conducted within 14 calendar
days of the occurrence of serious adverse event.
 In case if the investigator fails to report any serious adverse events within the
stipulated period, he shall have to furnish the reason for the delay to this
satisfaction of the licensing authority along with the report of serious adverse
events,

19.  Responsibility of the sponsor:
Any report of the serious adverse event, after due analysis shall be forwarded by the
sponsor to the licensing authority as, chairman of the ethics committee and the head
of the institution where the trial has been conducted within 14 calendar days of the
occurrence of the serious adverse effects.
 Responsibility of the Ethics committee:
In case of serious adverse event occurrence to the clinical subjects, the ethics
committee shall forward its report on the Serious Adverse event, after due analysis,
along with its opinion on the financial compensation, if any, to be paid by the
sponsor or his representative, whosoever had obtained permission from the licensing
authority as referred to in clause (b) of rule 21 for conducting the clinical trial to the
licensing authority within a specified time frame of the occurrence of the serious
adverse event.

20. UNITED STATES
 Responsibilities of the investigator:
 The investigator should immediately report to the sponsor any serious adverse
events, whether or not considered drug-related, including those listed in the
protocol or investigator brochure and must include an assessment of whether
there is a reasonable possibility that the drug caused the event.
 The US FDA is a cognizant of the fact that it may take investigator a short
period of time to compile information about the event, but they expect the
information to the immediately reporting to the sponsor.
 The investigator shall also promptly report to the IRB all changes in the
research activity and all unanticipated problems involving risk to human
subjects or others.

21.  Responsibilities of the sponsor
 The sponsor must notify FDA in all participating investigators in an IND safety
report of potential serious risks, from clinical trials or any other source, as soon
as possible, but in no case later than 15 calendar days after the sponsor
determines that the information qualifies for reporting as follows.

22. PHARMACOVIGILANCE PROGRAM IN INDIA
Pharmacovigilance Program in India was initiated and introduced by the Indian
regulatory authority (Central Drug Control Standard Organization). Ministry of
Health and Welfare under DCGI under CDSCO started with an aim to protect the
public health safety.
This is working under Steering Committee.

23. 2010
Launched by the Ministry of
Health and Welfare, Govt of
India in 2010 at AIIMS New
Delhi as National Coordinating
Centre (NCC)
April 2011
The program transferred to IPC
as NCC in 2011 by a notification
issued by the MoHFW, Govt of
India
July 2015
IPC-PvPI became the NCC for
Materiovigilance Program of
India (MvPI) from July 2015
July 2017
IPC, NCC-PvPI became a WHO
Collaborating Centre for
Pharmacovigilance in Public
Health Programmes &
Regulatory services

24. Mission of PvPI:
To safeguard the health of the Indian population by ensuring that the benefits of
use of medicine outweigh the risks associated with its use.
Vision of PvPI:
To improve the patient safety and welfare in Indian population by monitoring the
drug safety and thereby reducing the risks associated with the use of medicine.

25. Objective of PvPI:
To develop a national-wide system for patient safety monitoring.
To determine and examine the new signal (ADR) from the reported cases.
Examine benefit-risk ratio of marketed medications.
To create awareness among healthcare professionals about the importance of ADR
reporting in India.
Arise as a national centre of excellence for pharmacovigilance activities.

26. Who can report What to report Whom to report
Healthcare professionals
(clinicians, dentist, pharmacist,
nurses, and others) can report
suspected adverse drug
reaction. Pharmaceutical
companies can also send
ICSRs specific for their
product to NCC.
All types of suspected ADRs
irrespective of whether they are
known or unknown, serious and
non-serious, frequent or rare.
Although pharmacovigilance is
primarily concerned with
pharmaceutical medicines, adverse
reactions associated with drugs
used in traditional medicines (e.g.,
herbal remedies) should also be
considered
Use the ‘Suspected Adverse
Drug Reaction Reporting Form’
which is available on the official
website of IPC (www.ipc.gov.in)
as well as CDSCO
(www.cdsco.nic.in) to report any
ADR. A reporter who is not a
part of AMC can submit the
ICSR to the nearest AMC or
directly to the NCC.
Performance and Effectiveness of PV system:

28. PvPI phases:
It is a 5-year program and it consists of totally 5 phases.
i. Initial phase (2010-2011)
ii. Expansion and consolidation phase (2011-2012).
iii. Expansion and maintenance phase (2012-2013)
iv. Expansion and optimization phases (2013-2014)
v. The excellence phases (2014-2015).

29. i. Initial phase
 Developing systems and procedure
 Enrolment of 40 medical institute
 Start data collection from AEFI (Adverse Events following Immunization)
ii. Expansion and consolidation phase
 Linkage with UMC, Sweden
 Identify gaps and address via proper training
 Training of PV software supply by UMC, WHO
iii. Expansion and maintenance phase
 Enrolment of additional hundred medical institute
 Software development and validation
 Zonal workshop of drug safety public awareness

30. iv. Expansion and optimization phase
 Training of PV human resources.
 Newsletter publication of drug safety
 Enrol additional 100 medical colleges
v. Excellence phase
 Create Centre of Excellence for Pharmacovigilance in Asia Pacific

31. Communication under PvPI

32. Committees of NCC:
 Steering Committee
 Working Group
 Quality Review Panel
 Signal Review Panel
 Core Training Panel
Different modes of communications used in PvPI:
a) Press and Media Communication
b) Website
c) Newsletter

34. CONCLUSION
Pharmacovigilance is the only way to ensure the safety of the drug throughout
the life cycle. Now it is considered as user-friendly network for reporting the
adverse events. Hence by determining the adverse reaction we can make an
alternative solution in order to overcome the adverse events and hence it can be
recovered

35. REFERENCES
1. Mohanta G P, Manna P K. Textbook of Pharmacovigilance Concepts and Practice. 2nd ed. Hyderabad: PharmaMed Press,
2020; P: 1-8, 12-26.
2. Charylu R N, Jose J. Pharmaceutical Regulatory Science. Pune: Nirali Prakashan, 2021; P: 4.21-4.24.
3. Baweja H. Textbook of Clinical Research. Punjab: S Vikas and Company, 2021; P: 136- 149, 214- 221.
4. Tripathi D K, Shukla S S, Pandey R K. Textbook of Pharmacovigilance. 2nd ed. Pune: Nirali Prakashan, 2021; P:1.11-
1.114.
5. ICH website: www.ipc.gov.in (accessed on 6 febrauary 2022)
6. Jaani M, Nagasamy V D, Pharmacovigilance- A Master key for Drug Safety. J. Pharm. Sci. & Res. Vol. 11(5), 2019, 1963-
1970.
7. Chin R, Bairu M. Global Clinical Trials Playbook. Chapter 13. Pharmacovigilance and Risk Management, 2012; P: 141-
159.
8. Anusha L, Aashrita M, Sridhar R. A review of Pharmacovigilance and its importance. World J Pharm Pharm Sci. 2017;
Volume 6, Issue 1, 300-310.

36. THANK YOU