National Coordination Centre - ipc.nic.inipc.nic.in/writereaddata/linkimages/3guidance documnet-7291665005.pdf · drugs in India to meet acceptable standards of quality, safety and

Guidance Document For Reporting Individual Case Safety Report

Pharmacovigilance Programme of India Page 1

National Coordination Centre

Indian Pharmacopoeia Commission, Ghaziabad is an autonomous institution of the Ministry

of Health and Family Welfare, Govt. of India, which sets standards for drugs that are

manufactured, sold and consumed in India.IPC is functioning as a National Coordination

Centre for Pharmacovigilance Programme of India.The basic function of IPC is to publish

official documents for improving quality of medicines by way of adding new and updating

existing monographs in the form of Indian Pharmacopoeia. It further promotes rational use of

generic medicines by publishing National Formulary of India. IP prescribes standards for

identity, purity and strength of drugs essentially required from healthcare perspective of

human beings and animals. IPC also provides IP Reference Substances which act as a finger

print for identification of an article under test and its purity as prescribed in IP. The IP

standards are legally acceptable during quality assurance and at the time of dispute in the

court of law. IPC administers the Second Schedule of the Drugs and Cosmetics Act, 1940

(the act) and Rules 1945, applying a risk management approach designed to set standards of

drugs in India to meet acceptable standards of quality, safety and efficacy of drugs commonly

required for treatment of diseases prevailing in the region.

NCC is operating under the supervision of steering committee which recommends procedures

and guidelines for regulatory interventions.The main responsibility of NCC is to monitor all

the adverse reactions of medicines being observed in the Indian population. It aims to

develop and maintain its own Pharmacovigilance database for patient safety with respect to

use of medicine.



Introduction

Adverse reactions of drugs continue to remain as an important public health issue. Safety

monitoring of medicines is the responsibility of all stakeholders of the healthcare system

since globally it continues to be an important cause of morbidity and mortality. In some

countries adverse drug reactions are among the ten leading causes of mortality. The safety of

patients and the safe use of medicines are crucial for health policy development and delivery

of the best healthcare. To prevent or reduce harm to patients thereby improving public health,

the safety of medicines in clinical use must be monitored and evaluated through specialised

systems. This requires a need to establish a well-organised pharmacovigilance system. Thus,

a pharmacovigilance system is defined as a system used by an organisation to monitor the

safety of authorised medicinal products and detect any change to their risk-benefit balance. A

pharmacovigilance system is characterised by its structures, processes and outcomes. To run

an effective pharmacovigilance system a protocol is required for reporting adverse reactions

associated with drug use. Therefore NCC aims to ensure the systematic and effective

functioning of PvPI by publishing its guidance document.

This Guidance Document lays down requirements and guidance for reporting of adverse drug

reactions and significant safety issues related to drugs regulated by the Central Drugs

Standard Control Organization. This document does not establish legally enforceable

responsibilities. This has been prepared by the NCC and approved by Working Group. The

purpose of this document is to present the importance of pharmacovigilance in India, to

record the growth and potential as a significant discipline within medical science, and to

describe its impact on patient welfare and public health. This document also highlights the

importance of collaboration and communication at local, regional and international levels to

ensure that pharmacovigilance delivers its full benefits. It also provides guidance to

stakeholders on good pharmacovigilance practices, assessment of data regarding drugs

including vaccines, herbal and biological products (blood and blood components) and dietary

supplements.

Scope of Guidance Document

This document helps to expand the role and scope of PvPI to identify, analyse and minimise

the risk associated with drugs. Further it promotes better and broader use of existing

pharmacovigilance data for patient safety by spontaneous reporting system.



The document is intended for the following wide-ranging readership:

Policy makers at all levels of healthcare, particularly those concerned with drug

policy

Staff and consultants in CDSCO

Healthcare practitioners including clinicians, dentists, pharmacists, nurses and other

healthcare professionals

Pharmaceutical industry and scientists

Professional staff at NCC

Representatives of Adverse Drug Reaction Monitoring Centre

Medical and scientific journals

Health epidemiologists

Health economists

National Health Programs under MoHFW, Government of India

Professional staff at poison and drug information centres

Health administrators

Consumer groups, civil societies and patient support groups

Institutes of medical, dental, pharmacy and nursing



Chapter 1: Pharmacovigilance Programme of India

1.0 Background

The Pharmacovigilance Programme of India was initiated by the Government of India on 14th

July 2010in AIIMS, New Delhi as the NCC for monitoring ADRs in the country for safe-

guarding public health. The NCC was shifted from AIIMS, New Delhi to IPC, Ghaziabad on

15th

April 2011.

1.1 Overview

Before registration and marketing of medicine in the country, its safety and efficacy

experience is based primarily on the use of the medicine in clinical trials. These trials mainly

detect common adverse reactions. Some important reactions, such as those, which take a long

time to develop, or those, which occur rarely, may not be detected in clinical trials. In

addition, the controlled conditions under which medicines are used in clinical trials do not

necessarily reflect the way they will be used in practice. For a medicine to be considered

safe, its expected benefits should be greater than any associated risks of harmful reactions. So

in order to gain a comprehensive safety profile of medicine, a continuous post-marketing

monitoring system is essential. PvPI is to collate the data and use the inferences to

recommend regulatory interventions, besides communicating risks to healthcare professionals

and the public.

The robust database will play a vital role in analysing and detecting new signals and updating

the status of existing information on drug profile. The larger is the data for any drug, the

higher will be the likelihood of saying with confidence that the conclusions or inferences

being drawn from that data are meaningful and significant. The Medical Colleges and

hospitals are the corner stone of the PvPI. They act as AMCs which are responsible for

collecting the individual case safety reports and performing the follow up with the patient to

check completeness of the reports as per SOPs. The ICSRs data is then uploaded in the

VigiBase by using VigiFlow software which is sent to NCC. The quality assessment will be

performed at NCC and the data is further sent to WHO-UMC which maintains the global

drug safety database.



1.2 Mission

Safeguard the health of the Indian population by ensuring that the benefits of use of medicine

outweigh the risks associated with its use.

1.3 Vision

To improve patient safety and welfare in Indian population by monitoring drug safety and

thereby reducing the risk associated with use of medicines.

1.4 Objectives

To create a nation-wide system for patient safety reporting

To identify and analyse new signal from the reported cases

To analyse the benefit - risk ratio of marketed medications

To generate evidence based information on safety of medicines

To support regulatory agencies in the decision-making process on use of medications

To communicate the safety information on use of medicines to various stakeholders to

minimise the risk

To emerge as a national centre of excellence for pharmacovigilance activities

To collaborate with other national centres for the exchange of information and data

management

To provide training and consultancy support to other national pharmacovigilance

centres across globe

1.4.1 Short term goals

To develop and implement pharmacovigilance system in India

To enrol, initially, all MCI approved medical colleges in the program covering north,

south, east and west of India

To encourage healthcare professionals in reporting of adverse reaction to drugs,

vaccines, medical devices and biological products

Collection of case reports and data

1.4.2 Long term goals

To expand the pharmacovigilance programme to all hospitals (govt. & private) and

centres of public health programs located across India

To develop and implement electronic reporting system (e-reporting)

To develop reporting culture amongst healthcare professionals

To make ADR reporting mandatory for healthcare professionals



1.5 Organogram under Pharmacovigilance Programme of India

1.5.1 Organogram of NCC

1.5.2 Committees under NCC

The following committees and panels are constituted by MoHFW, Government of India to

give proper direction for efficient functioning of the programme.

Steering Committee

PvPI is administered and monitored by Steering Committee to supervise and give proper

direction to the programme.

PvPI Working Group

It is constituted to approve major technical issues related to establishment, implementation of

programme and giving technical inputs to CDSCO for regulatory intervention of medicine.

Finance & Account Officer Senior Scientific Officer

Technical Associate

Secretary-Cum-

Scientific Director,

IPC

Director, National

Institute of

Biologicals

Scientific Assistant

Advisor



Quality Review Panel

It is constituted to review quality, causality assessment and completeness of ICSRs. The

panel also makes recommendations to PvPI working group after data analysis and will devise

formats and guidance documents for follow up actions after implementation of

recommendations.

Signal Review Panel

It is constituted of experienced scientists and clinical experts affiliated to government and

non-government academic institutions, hospitals and pharmaceutical industries to collate and

analyze information from ICSRs submitted to NCC. This panel assesses the results of the

regular computerized screening of ICSRs in NCC database for the occurrence of signals of

possible importance of public health, drug regulation and science. It also defines biostatical

methods to be followed for analysis and creates standardized post analytical reports that will

help in understanding the information that is derived from ADRs. It is also responsible to

decide on actionable indicators.

Core Training Panel

The Core Training Panel of PvPI identifies trainers and zone wise training centres for

imparting training under pharmacovigilance training programme. Core training panel

interacts with international agencies for participation and implementation of training

programmes related to pharmacovigilance. It organizes training and projects budgetary

requirements. Training modules and training schedules are also develop by this panel.

1.6 PvPI - Programme Communication

Effective communication channels are the key to successful functioning of PvPI. The

following chart depicts the movement of information between the key stakeholders and

ensures the continuous transfer of data, information, and knowledge.



PvPI - Programme Communication



Chapter 2: Responsibilities of Stakeholders under

PvPI

2.0 Roles and Responsibilities of Personnel at AMC

Each AMC under PvPI is assigned with a coordinator and a technical associate responsible

for its functioning. Their roles and responsibilities are:

The designated coordinator is responsible for the proper functioning of respective

AMC. In absence of the coordinator, the designed deputy coordinator is responsible

for the smooth functioning of the centre.

Other important responsibilities of coordinator checking completeness of a valid case,

causality assessment and scrutinizing the ADR reports as per SOPs.

The technical associate is responsible for collecting and follows up ICSRs. All the

scrutinized and signed ADR reports should be entered in VigiFlow by TA. Every

report has to be sent for the central assessment at NCC.

The centre coordinator is responsible for sending the monthly reports of their AMC to

NCC.

The centre coordinator is also responsible for sensitization of the physicians/healthcare

professionals/medical students/patient of the catchment hospital for spontaneous ADR

reporting by various modes (lectures on ADR reporting, emails, telephone, pamphlets

& newsletters).

Feedbacks to all healthcare professionals involved in reporting are to be sent by the

AMC coordinator.

2.1 Roles and Responsibilities of Personnel at NCC

NCC is responsible for:

Preparing standard operating procedures, guidance documents &training manuals.

Enrolment of new AMC.

Reviewing and analyzing ICSRs received from AMCs and commit them to WHO-

UMC.

Organising Continuous Medical Education on pharmacovigilance at various zones.

Conducting periodic training and workshops for all enrolled AMCs.

Publishing the newsletter (PvPI Newsletter) on timely basis.

Reporting all concerned issues to CDSCO Headquarters.

Providing procurement, financial and administrative support to all AMCs enrolled

under PvPI.

Collaborating with WHO-UMC, Sweden.



2.2 Roles and Responsibilities of Personnel at Zonal/Sub-zonal CDSCO

office

The Zonal/Sub-zonal is responsible for:

Reporting all drug related issues to the CDSCO headquarter.

Providing administrative and logistic supports to the AMC at their zone.

Auditing/inspecting AMC in their respective zonal and submitting the inspection

report to CDSCO HQ.

2.3 Roles and Responsibilities of Personnel at CDSCO HQ

The CDSCO HQ is responsible for:

Taking appropriate regulatory decision and actions on the basis of recommendations

made by NCC.

Propagating medicine safety related decisions to stakeholders.

Providing administrative support to run PVPI.



Chapter 3: Reporting of Adverse Drug Reactions

Monitoring of ADRs in a pharmacovigilance involves both active and passive surveillance

system. Passive surveillance means that no active measures are taken to look for adverse

effects other than the encouragement of health professionals and others to report safety

concerns. Reporting is entirely dependent on the initiative and motivation of the potential

reporters. Spontaneous or voluntary reporting is a type of passive surveillance. Active

surveillance, in contrast to passive surveillance, seeks to ascertain completely the number of

adverse events via a continuous pre-organised process. An example of active surveillance is

the follow-up of patients treated with a particular drug through a risk management program.

3.0 Spontaneous Reporting

As per WHO definition, a spontaneous report is an unsolicited communication by healthcare

professionals or consumers, pharmaceutical company to regulatory authority that describes

one or more suspected adverse drug reactions in a patient given one or more medicinal

products. Globally spontaneous reporting is adopted as the most common method of passive

surveillance since it is easiest to establish and the convenient to run. In spontaneous

reporting, reporting rates are generally very low and subject to bias and there is no database

of all users or information on overall drug utilization. These problems prevent the accurate

assessment of risk, risk factors or comparisons between drugs. Underreporting is also a

problem of spontaneous reporting systems for suspected adverse drug reactions. Under-

reporting may delay signal detection and cause underestimation of a serious problem.

Nevertheless spontaneous reporting has played a major role in the identification of safety

signals throughout the marketed lifetime of medicines in general. PvPI is following

spontaneous reporting system to collect data on drug safety.

3.1 Reporting Form

The NCC has designed a Suspected Adverse Drug Reaction Reporting Form to record

adverse reactions related to drugs. Separate forms are available to record adverse reactions

associated with transfusion of blood and blood products and Adverse Event Following

Immunization. A report that contains information describing a suspected adverse drug

reaction related to the administration of one or more medicinal products to an individual

patient is termed as individual case safety report. An ICSR must contain information on the

following items:



A. Patient Information

1. Patient initials: A reporter should only write the initials of a patient instead of full

name. For e.g.: Madhu Gupta should be written as MG

2. Age at time of event or date of birth: A reporter must report either the date of birth or

age of the patient at the time event or reaction occurred

3. Sex: A reporter must mention the gender of the patient.

4. Weight: The weight of the patient should be in kilograms

B. Suspected Adverse Reaction

5. Date of reaction started: A reporter must report the date on which the reaction first

observed.

6. Date of recovery: If the reaction recovered, the date on which the reaction recovered

should be report.

7. Describe reaction: A reporter must describe the event in terms of nature, localization

etc. For e.g.: patient developed erythematous maculopapular rash over upper and

lower limp.

C. Suspected Medications

8. The details of suspected medication(s) such as drug name (brand or generic name),

manufacturer, batch no/lot no, expiry date, dose used, route used, frequency, dates of

therapy started and stopped, and indication of use must be provided by the reporter.

9. De-challenge details: A reporter must report the status on de-challenge as:

‘Yes’- if reaction abated after de-challenge

‘No’- if reaction does not abated after de-challenge

‘Unknown’- if information on de-challenge is not confirmed

‘Not Applicable’ or ‘NA’- if de-challenge is not applicable as in case of

vaccines, anaesthesia or where single dose is given

‘Reduced dose’- If dose at which the reaction occurred is reduced

Note: Also mention the reduced dose

10. Re-challenge details: A reporter must report the status on re-challenge as:

‘Yes’- if reaction reappeared after re-challenge

‘No’- if reaction does not reappeared after re-challenge



‘Unknown’- if information on re-challenge is not confirmed

‘Not Applicable’ or ‘NA’- if re-challenge is not applicable as in case of

injections.

‘Re-introduced dose’- If the reduced dose is increased to dose at which adverse

event occurred

11. Concomitant drugs: A reporter should include all the details of concomitant drugs

including self-medication, OTC medication, herbal remedies with therapy dates

12. Relevant tests/ laboratory data: The reporter must report any laboratory data (if

available) relevant to the event occurred.

13. Other relevant history: A reporter must mention any relevant history persistent to

patient including pre-existing medical conditions (e.g. allergies, pregnancy, smoking,

alcohol use, hepatic/renal dysfunction).

14. Seriousness of the reaction: If any event is serious in nature, a reporter must tick the

appropriate reason for seriousness as:

‘Death’- if the patient died due to adverse event

‘Life-threatening’- if patient was at substantial risk of dying at the time of the

adverse event

‘Hospitalisation/prolonged’- if the adverse event cause hospitalisation or

increased the hospital stay of the patient

‘Disability’- if adverse event resulted in a substantial disruption of a person's

ability to conduct normal life functions

‘Congenital anomaly’- if exposure of drug prior to conception or during

pregnancy may have resulted in an adverse outcome in the child.

‘Required intervention to prevent permanent impairment/damage’- if

medical or surgical intervention was necessary to preclude permanent impairment

of a body function, or prevent permanent damage to a body structure

‘Other’ -when the event does not fit the other outcomes, but the event may put

the patient at risk and may require medical or surgical intervention to prevent one

of the other outcomes. Examples include serious blood dyscrasias (blood

disorders) or seizures/convulsions that do not result in hospitalization,

development of drug dependence or drug abuse



15. Outcomes: The reporter must tick the outcome of the event as:

‘Fatal’- if the patient dies due to adverse event

‘Continuing’- if the patient is continuing with the event occurred

‘Recovering’- if the patient is recovering from the existing event occurred

‘Recovered’- if the patient is recovered from the event occurred

‘Unknown’- if the outcome is not known

D. Reporter

16. Name and Professional address: A reporter must mention his/her name and

professional address on the form. The identity of the reporter will be maintained

confidential

17. Causality assessment: The reporter (if trained) must perform the causality assessment.

18. Date of report: A reporter must mention the date on which he/she reported the adverse

event.

For quality reporting of ICSRs all the above mentioned fields are essential. In case of

incomplete information, the reporter must take care that at least mandatory fields are present.

Following are the mandatory fields for a valid case report:

Patient information: initials, age at onset of reaction, gender.

Suspected adverse reaction: A reaction term(s), date of onset of reaction

Suspected medication: Drug(s) name, dose, date of therapy started, indication of use,

seriousness, outcome, de-challenge and re-challenge details

Reporter: Name and address, causality assessment, date of report





3.2 Who can Report?

Under PvPI healthcare professionals (clinician, dentist pharmacist nurses and others) can

report suspected adverse drug reaction. Pharmaceutical companies can also send ICSRs

specific for their product to NCC.

3.3 What to Report?

In order to foster the habit of reporting PvPI encourages reporting of 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 medicine (e.g. herbal remedies)

should also be considered. Special fields of interest are drug use in pregnancy, lactation,

paediatric and geriatric. In addition, the reporting of lack of efficacy and suspected

pharmaceutical defects is recommended, especially when there is the possibility of

manufacturing problems, counterfeit pharmaceuticals or of the development of resistance e.g.

antibiotics.

3.4 Whom to Report?

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. A reporter can also mail the ICSR at [email protected] or

[email protected]

Contact details for AMCs under PvPI are included in Annexure I.

3.5 Establishment of an AMC

A ‘letter of Intent’ is required to submit by the Heads of the Institutions to participate in this

nationwide programme to monitor drug safety. After examining the suitability, the concerned

centre may be inducted as AMC under PvPI. Subsequently NCC communicates the AMC

details to WHO-Uppsala Monitoring Centre (UMC), Sweden to obtain VigiFlow (WHO-

UMC owned online software) login details to upload ADRs.

http://www.ipc.gov.in/

http://www.cdsco.nic.in/

mailto:[email protected]




3.5.1 Data Flow

Once the Medical institute enrolled as AMC, the AMC starts reporting ADRs to NCC.

Following chart explains the flow of data at regional, national and international level.

Following chart explains the flow of data at regional, national and international level.

3.6 Assessment of Individual Case Safety Reports

The quality of the ICSR will be assessed for completeness of information and it will be

reviewed by:

1. Quality of documentation: e.g. completeness and integrity of data, quality of diagnosis,

follow-up.

2. Coding: Drug names should be registered in a systematic way, for example by using the

WHO Drug Dictionary (which is based on the ATC classification). For the coding of the

adverse events the WHO Adverse Reaction Terminology (WHOART) and internationally

recognised terminology (e.g. MedDRA) should be used.

3. Relevance with regard to the detection of new reactions, drug regulation, or scientific or

educational value. The following questions especially may be asked:



New drug - a new drug shall continue to be considered as new drug for a period of

four years from the date of its first approval or its inclusion in IP, whichever is

earlier.

Unknown reaction- Not included in the approved Summary of Product

Characteristics

Serious reaction- Results into either death, life-threatening condition,

hospitalisation or prolonged hospitalisation, disability, congenital anomaly,

required intervention to prevent permanent impairment/damage or any other

medically important condition

4. Identification of duplicate reports: Certain characteristics of a case (sex, age or date of

birth, dates of drug exposure, etc.) may be used to identify duplicate reporting.

5. Causality assessment: With few exceptions, case reports describe suspected adverse drug

reactions. The likelihood of a causal relationship between drug exposure and adverse

events must be validated.

3.7 Utilization of the Data

Data collected in pharmacovigilance can be used in a variety of ways.

1. Signal generation and strengthening: A major aim of pharmacovigilance is the early

detection of signals with regard to possible adverse reactions. A signal may be

strengthened by further analysis can help the regulatory system in performing regulatory

activities.

2. Drug regulation: After approval of a medicinal product, all available domestic and

international safety information is continuously monitored by the drug regulatory

authority and MAH. The PvPI data can be useful in resolving the problems by adaptation

of the approved product information (inclusion of new adverse effects and warnings).

3. Education: The information from PvPI data is useful in updating the knowledge of

healthcare professionals during continuous medical education programme on

pharmacovigilance.



3.8 Reporting Requirements in Special Population

3.8.1 Pregnancy and Breastfeeding

Pregnancy

The clinical trial program of a medicinal product under development rarely includes pregnant

women, unless the product is intended specifically for use during pregnancy. All pregnant

women coming for routine pre-natal check-ups at various categories of health system must be

monitored for any suspected ADR by the healthcare professional. They must be followed-up

to collect information on the outcome of the pregnancy and development of the child after

birth. At present NCC database contains a limited number of ICSRs related to parent-child

case. Intensive monitoring is required to draw any conclusion to upgrade/downgrade

pregnancy category of drugs use during pregnancy.

Breastfeeding

All lactating mother exposed to medicinal product should be monitored to collect information

on outcome of lactation on neonates and infants.

3.8.2 Paediatric and Geriatrics

The collection of safety information in the paediatric and geriatric population is important as

ADRs can lead to significant morbidity and death among these populations. Immunisation is

one of the most common and widely used public health interventions in paediatric population.

On other hand geriatric population is at higher risk of developing ADRs due to factors like

polypharmacy and co-morbidities. The paediatric and geriatric population can be considered

to be more vulnerable to some adverse reactions. Therefore, data collected from this program

will provide a national database for drug safety information in this vulnerable population. To

ensure safe and effective medicines for children and elderly, efforts are needed at different

levels (governments, drug regulatory agencies, pharmaceutical industries, health care

professionals, and parents).NCC database contains ICSRs reported for paediatric population

and geriatric population but more number of case reports are required for monitoring drug

safety in these populations.



3.8.3 Reporting in the Event of a Public Health Emergency

A public health emergency is a public health threat duly recognised either by the WHO or

MoHFW, Government of India. In the event of a public health emergency, regular reporting

requirements may be amended.

3.8.4 Reports of overdose, abuse, off-label use, misuse or OTC

Reporting of ADRs encountered with overdose, abuse, off-label use, misuse or occupational

exposure is not currently included in PvPI, however physician judgement shall be final.



Chapter 4: Haemovigilance

4.0 Introduction

Haemovigilance is a process of data collection and analysis of transfusion -related adverse

reactions in order to investigate their causes and outcomes, and prevent their occurrence or

recurrence. Indian Pharmacopoeia Commission in collaboration with National Institute of

Biologicals has launched Haemovigilance across the country under PvPI with following

terms of references:

1. To track Adverse Reactions/ Events and incidence associated with Biologicals,

Blood transfusion and Blood product administration (Haemovigilance) as well as

tissue organ and cell therapy transplantation.

2. To help in identifying trends, recommend best practices and interventions required

to improve patient care and safety, while reducing overall cost of the healthcare

system.

Haemovigilance Programme was launched on 10th Dec 2012 as an integral part of PvPI. NIB

is the Coordinating Centre to collate & analyze data for Haemovigilance.

Further information on Haemovigilance is available on http://nib.gov.in/haemovigilance.

http://nib.gov.in/haemovigilance.



4.1 Transfusion Reaction Reporting Form(TRRF)



Chapter 5: Adverse Event following Immunization

5.0 Introduction

AEFI is defined as a medical event that takes place after immunization, causes concern and is

believed to be caused by immunization. The AEFI should be handled effectively in order to

maintain/restore public faith in immunization program. AEFI Surveillance System in India

has come a long way since its inception in 1986.

To ensure their safety and efficacy, vaccines are subjected to release a lot at Central Research

Institute, Kasauli before release for public use. AEFIs may occur due to the intrinsic property

of vaccines and constituents like stabilizers, adjuvant, antibiotics, diluents etc. added to the

vaccines or hypersensitivity of some individuals to vaccine component(s). Such incidents are

rare but may become apparent in terms of number when vaccinating a large cohort. AEFI

may also result from programmatic errors as a result of inappropriate storage, improper

handling, preparation and administration etc. of vaccines. AEFI surveillance and timely

management will build public confidence and prevent additional clustering of cases if they

occur due to a programmatic error.

AEFI surveillance monitors immunization safety, detects and responds to adverse events;

corrects unsafe immunization practices, reduces the negative impact of the event on health

and contributes to the quality of immunization activities. Operational Guidelines of AEFI

mainly relate to vaccines included in the National Immunization Program and issues of

vaccine manufacturing, safety & quality control of AEFI cases are handled by CDSCO

headed by DCGI. Intensive efforts are being made by MoHFW, Government of India to

strengthen surveillance and monitoring of AEFI in the country. In India, the safety of vaccine

is monitored by the division of AEFI, MoHFW, Government of India and PvPI.

AEFI cases submitted to PvPI are further coordinated with national level committee AEFI for

reporting & investigation. Subsequently AEFI committee will follow with local AEFI team to

completely furnish FIR/PIR/DIR to do the causality assessment.



5.1 Adverse events following immunization- Reporting Form



















Chapter 6:Causality Assessment of Adverse Event

6.0 Definition

Causality Assessment is defined as the evaluation of the likelihood that a medicine was the

causative agent of an observed adverse reaction.

6.1 Why causality assessment?

An inherent problem in pharmacovigilance is that most case reports concern suspected

adverse drug reactions. Adverse reactions are rarely specific for the drug, diagnostic tests are

usually absent and a Re-challenge is rarely ethically justified. In practice few adverse

reactions are ‘certain’ or ‘unlikely’; most are somewhere in between these extremes, i.e.

‘Possible’ or ‘Probable’. In an attempt to solve this problem many systems have been

developed for a structured and harmonised assessment of causality but none of these systems,

have shown to produce a precise and reliable quantitative estimation of relationship.

Nevertheless, causality assessment has become a common routine procedure in

pharmacovigilance.

AMC is responsible for performing causality assessment of reports which shall be reviewed

at NCC. The PvPI follows WHO-UMC causality assessment scale for establishing the

relation between the suspected drug and suspected adverse drug event. The WHO-UMC scale

is used as a practical tool for the assessment of case reports. It is basically a combined

assessment taking into account the clinical-pharmacological aspects of the case history and

the quality of the documentation of the observation.

6.2 Advances and limitations of standardised case causality assessment

What causality assessment can do What causality assessment cannot do

Decrease disagreement between assessors Give accurate quantitative measurement of

Relationship likelihood

Classify relationship likelihood Distinguish valid from invalid cases

Mark individual case reports Prove the connection between drug and event

Improvement of scientific evaluation;

Educational

Quantify the contribution of a drug to the

Development of an adverse event

Change uncertainty into certainty



6.3 WHO-UMC Causality Assessment Scale

Causality term

Assessment criteria

Certain

Event or laboratory test abnormality, with plausible time

relationship to drug intake

Cannot be explained by disease or other drugs

Response to withdrawal plausible (pharmacologically,

pathologically)

Event definitive pharmacologically or phenomenological

(i.e. an objective and specific medical disorder or a

recognised pharmacological phenomenon)

Re-challenge satisfactory, if necessary

Probable/

Likely

Event or laboratory test abnormality, with reasonable time


Unlikely to be attributed to disease or other drugs

Response to withdrawal clinically reasonable

Re-challenge not required

Possible

Event or laboratory test abnormality, with reasonable time


Could also be explained by disease or other drugs

Information on drug withdrawal may be lacking or unclear

Unlikely

Event or laboratory test abnormality, with a time to drug

intake that makes a relationship improbable (but not

impossible)

Disease or other drugs provide plausible explanations

Conditional/

Unclassified

Event or laboratory test abnormality

More data for proper assessment needed, or

Additional data under examination

Unassessable/

Unclassifiable

Report suggesting an adverse reaction

Cannot be judged because information is insufficient or

contradictory

Data cannot be supplemented or verified



Chapter 7: Signal Detection and Evaluation

Signal detection and its clinical assessment is an important domain of pharmacovigilance.

The WHO has defined a Signal as “Reported information on a possible causal relationship

between an adverse event and a drug, the relationship being unknown or incompletely

documented previously.” It is worth mentioning that a signal does not imply causation but it

can only provide preliminary information about postulating a hypothesis and not for testing it.

Analysis of any pharmacovigilance database can be used for signal detection but it is

reviewed by clinicians and other experts to arrive at decision making.

Signal detection process in a spontaneous ADR database is based on different statistical

methodology - either the Bayesian or Frequentist statistical approach. Whichever method is

employed, basically it involves computation of measures of disproportionality i.e.

determination to what extent the number of observed cases differs from the number of

expected cases. All disproportionality algorithms despite having operational technique

variability actually calculate surrogate observed to expected ratios in which the reporting

experience of each reported drug-adverse event combination is compared to the background

reporting experience across all drugs and events in the database using an independence

model.

The WHO UMC uses the BCPNN – (Bayesian Confidence Propagation Neural Network)

while US FDA uses the MGPS- (Multi item Gamma Poisson Shrinker) methodologies. Other

disproportionality analyses methods are ROR (Reporting Odds Ratio), PRR (Proportional

Reporting Ratio) are employed by some national reporting centres (MHRA, UK) and drug

safety research units.

In the BCPNN methodology computation of the Information Component is based on prior

and posterior probabilities. As per the WHO-UMC, the IC measures the disproportionality in

the reporting of a drug-ADR pair in an ICSR database, relative to the reporting expected

based on the overall reporting of the drug and the ADR. Positive IC values indicate higher

reporting than expected. However, review of signals generated by using such tools must be

analysed by clinicians and drug safety experts before arriving at a conclusion.

Whichever method is used for signal detection, each has its advantages and disadvantages

and therefore is no single method which can be considered as the gold standard. The PVPI is



currently analysing its own national database and a signal review panel will shortly formulate

its strategy for signal detection and its assessment.



Chapter 8: PvPI and WHO-UMC Collaboration

IPC-NCC has free access to the databases provided by WHO-UMC which helps in achieving

the objectives of PvPI in a more efficient way.

8.0 VigiFlow

VigiFlow is a web-based ICSR management system that is specially designed for use by

national centres in the WHO Programme for International Drug Monitoring. VigiFlow is

based on and compliant with the ICH E2B standard and is a trademark of the UMC and

maintained by the UMC in Uppsala, Sweden. It offers a simple, fast and secure web-based

solution that improves all aspects of ADR reporting. ICSR data can be manually entered into

VigiFlow with support from the latest versions of terminologies such as the WHO-DD and

WHO-ART or MedDRA. Once a report is complete and committed the first version of the

ICSR is considered to be finalized. It is easy to retrieve reports to amend the contents or add

follow-up information. ICSRs will automatically be flagged for being copied to VigiBase, the

WHO Global ICSR database when they are committed.

8.1 VigiMed

VigiMed is a web-based forum for those working at national centres in the WHO Programme

to have easy access to safety concerns in other countries, to check regulatory status, and to

expedite the sharing of drug information. VigiMed is part of the UMC collaboration portal, a

web-based platform managed by the UMC.

8.2 VigiSearch

VigiSearch is a powerful search tool that provides access to all case reports in VigiBase.

VigiSearch allows for report searching across multiple drugs and ADRs simultaneously, as

well as incorporating a range of filters. Drugs can be searched on a generic substance level or

a specific trade name. VigiSearch also supports browsing the ATC structure. The results can

be accessed on an overview level and viewed from a number of aspects (country, year,

reaction term) or at the level of individual case report. For members of the WHO Programme,

VigiSearch enables an international comparison of national spontaneous reporting data, as

well as giving access to ADR information on drugs that are not yet on the national market.



8.3 VigiLyze

VigiLyze is a powerful search and analysis tool that provides access to more than 8 million

ICSRs in VigiBase, submitted from over 100 countries. VigiLyze includes data on

conventional medicines, traditional medicines as well as biological medicines including

vaccines. VigiLyze can be used to have a global, regional or national view of an ADR

identify or monitor international patient safety data. It can be useful to find supporting

evidence while assessing Indian case reports or to see how Indian data support global

pharmacovigilance. VigiLyze enables international comparison with national spontaneous

reporting data, as well as giving access to ADR information on drugs that are not yet on our

national market. Results from VigiLyze are instantly available as graphics as well as in

tabular format.



LOG-IN DETAIL

Change Password

Retrieve Unsaved Report

Language

Main Menu

Mandatory Fields: Report Title, Patient Initials, Patient Age, Gender, Reaction term, Onset Date of Reaction, Drug Name, date of therapy started, indication of use,

seriousness, outcome, de-challenge , re-challenge details, reporter details

1 2 3 4

VigiFlow- Demo Chart

User ID Password

Quick Start



5 6 7

THE CAUSALITY ASSESSMENT

SAVE REPORT

SEND REPORT TO NCC

COMMIT REPORT



Chapter 9: Risk Management, Communication and

Publications

9.0 Risk Management

Risk management is the identification, assessment, and prioritization of risks followed by

coordinated and economical application of resources to minimize, monitor, and control the

probability and impact of unfortunate events. It is the discipline within pharmacovigilance

that is responsible for signal detection and the monitoring of the risk-benefit profile of drugs.

At the time of marketing authorisation, the benefit-risk balance is judged to be positive for

the target population. A medicinal product is associated with multiple risks and individual

risks will vary in terms of severity, effect on individual patients and public health impact.

However, at the time when an initial authorisation is sought all the risks (actual or potential)

have not been identified and many of the risks associated with the use of a medicinal product

will only be discovered and characterised during post-authorisation.

Risk management has three stages which are inter-related as mentioned below:

1. Characterisation of the safety profile of the medicinal product including what is

known and not known.

2. Planning of pharmacovigilance activities is to characterise and identify new risks and

increase the knowledge in general about the safety profile of the medicinal product.

3. Planning and implementation of risk minimisation, mitigation and assessment of the

effectiveness of these activities.

Risk management is a global activity. However the benefits and risk of a medicinal product

may also vary between regions as they differ in disease prevalence, severity, population

genetics (South Indian, North Indian, East Indian and West Indian). The overall aim of risk

management is to ensure that the benefits of a particular medicinal product exceed the risks

by the greatest achievable margin for the individual patient and for the target population as a

whole.

9.1 Communication

Communicating safety information to patients and healthcare professionals is a public health

responsibility and is essential for achieving the objectives of pharmacovigilance in terms of

promoting the rational, safe and effective use of medicine, preventing harm from adverse



reactions and contributing to the protection of public health. Communication in PvPI

improves patient care, understanding, promotes transparency and accountability. All the

communications with WHO-UMC will be managed by NCC. All the issues associated with

drug safety are reported to CDSCO which will further take appropriate regulatory decision

and action on the basis of recommendation of NCC. The objective of communication in PvPI

aims to provide evidence based information on the safe and effective use of medicine and

regulatory status of medicines in India as well as globally. For this PvPI is using different

modes of communications as follow:

Press communication

It includes press release and press briefings which are primarily intended for journalists. The

Secretary-Cum-Scientific Director, IPC is the only designated authority to correspond with

media, related to all activities and issues of PvPI.

Website

A website is a key tool for the stakeholders including patients and health professionals. NCC

and CSDCO shall ensure that all important safety information should be published on the

websites under their control.

Newsletter

To communicate the findings and regulatory status of medicine in India as well as globally to

the stakeholders, IPC-NCC publishes newsletter i.e. “PvPI Newsletter” three issues in a year.

This newsletter is for everyone concerned with the issues of pharmacovigilance which

provides practical information and advice on drug safety and information about emerging

safety issues. The newsletter can also be downloaded from IPC website www.ipc.gov.in

under Pharmacovigilance Program of India.

9.2 Publications

IPC publishes Indian Pharmacopoeia, a book of standards for drugs in India as per Drugs and

Cosmetics Act, 1940 (the act) and Rules 1945. Also IPC publishes National Formulary of

India which is a guidance document for rational use of medicines.

http://www.ipc.gov.in/



Chapter 10: Audit of PvPI

To ensure the PvPI operates effectively and achieves its objectives, the center will establish

key indicators to measure the efficiency of (i) process (ii) outcome and (iii) impact of

the PvPI.

The following indicators will be measured:

A. Personnel’s details:

1. Personnel prior education and GVP experience.

2. Whether GVP training provided by the Zone/NCC

3. Do personnel know the job descriptions/responsibilities?

B. Administrative Responsibility:

1. Whether infrastructure is sufficient for PV?

2. Whether sufficient working place?

3. Whether logistic support provided by NCC such as Computer system, internet connection

are work properly?

4. Storage of hard copies as well as soft copies of documents.

5. Whether co-operation by other dept. to PV section?

C. Documents Review:

1. Verify version number and effective date of SOPs provided to NCC with AMC’s SOPs.

2. Verify Training Records/Certificates.

3. Randomly verify the data of source documents with entreated ICSRs.

D. Quality Assurance:

1. Does the source document mentions Essential Required Item such as patient information/

division/ reaction with date/ suspected drug with date/ outcome and sender information?

2. Determine whether data entry by TA in VigiFlow is same with source documents.

3. Whether all ADRs were reported in Suspected ADR Reporting Form.

4. Verify the timeline for reporting the SAE to NCC and CDSCO.

E. Data collection and its security:

1. Use of electronic data capture or data transcription from Suspected ADR Reporting into an

electronic record (VigiFlow).

2. Record retention.

3. Data security in case of disasters, e.g., power failure.

4. Contingency plans and backup files.

5. Determine whether personnel has Access methods e.g., User ID/password for the security

of electronic data.



F. Competence of Technical Associate:

1. He/She is conversant with the drug for which he/she is sending the report?

2. Is he/she conversant with the Rechallenge and Dechallenge process?

3. Is this a side effect or ADR?

4. Any SAE reported from the centre? How quickly it was forwarded.

G. Authenticity of Data:

1. Mechanism of identifying the patient from the registration number of the case report –

random check should be done by the inspecting team

2. How many times TA visits various wards.

3. How quickly he/she sends the report to NCC.

4. Is he/she taking interest in reporting drugs of current interest i.e. from CVS, Psychiatry,

Oncology and Diabetes?

5. Interaction with coordinator – frequency and documentation for the same.

H. Core Structural Indicators:

1. Does the AMC have standard accommodation?

2. Whether NCC has given acceptance letter?

3. A regular financial provision for the AMC?

4. Human resources to carry out its functions properly?

5. A standard ADR reporting form?

6. A process in place for collection, recording and entering of ADRs in VigiFlow?

7. Newsletters/NFI/Information bulletin/website for PV information dissemination?

8. A PV advisory committee or expert committee in the setting?

I. Core Process Indicators:

1. Total number of ADR reports reported to NCC last calendar year.

2. Percentage of total annual reports acknowledged by NCC.

3. Percentage of reports subjected to causality assessment in the year.

4. Percentage of reports on therapeutic ineffectiveness.

5. Percentage of reports on medication error.

6. Number of active surveillance activities initiated, on-going or completed, the last 5 years.

J. Core Outcome/Impact Indicators:

1. Number of medicine related hospital admissions/1000 admissions.

2. Number of medicine related deaths/1000 persons served by hospital.

3. Number of medicine related deaths/100000 in the population.

4. Average cost of treatment of medicine-related illness.

5. Average duration of extension of medicine-related hospital stay.

6. Average cost of medicine related hospitalization.





Annexure 1: Contact details of AMC reporting under PvPI

LIST OF 90 ADR MONITORING CENTRES UNDER PHARMACOVIGILANCE PROGRAMME OF INDIA (PvPI)

S. No State Centre Name Coordinator name Email

1. Andhra

Pradesh

Andhra Medical College King George Hospital

(KGH), Visakhapatnam

Dr. J. Sudha

[email protected]

2. Guntur Medical College, Guntur Dr. Zaheda Bano [email protected]

3. Kakatiya Medical College, Warangal Dr. Raju Devde [email protected]

4. Nizam Institute of Medical Sciences, Hyderabad Dr. Shobha Udutha [email protected]

5. Assam Department of Pharmacology, Govt. Medical

College, Guwahati

Dr. Mangala Lahkar [email protected]

6. Silchar Medical College & Hospital, Ghungoor,

Silchar

Dr.Pinaki Chakravarty [email protected]

7. Bihar Indira Gandhi Institute of Medical Sciences,

Shekhpura, Patna

Dr. Harihar Dikshit [email protected]

8. Goa Goa Medical College & Hospital, Bambolim Dr. Padmanabh V. Rataboli [email protected]

m

9. Gujarat SMT NHL Municipal Medical College,

Ahmadabad

Dr. Varsha J Patel [email protected]

10. BJ Medical College, Ahmadabad Dr. R.K. Dikshit [email protected]/ramdiksh

[email protected]

11. Government Medical College, Bhavnagar Dr. C B Tripathi [email protected]

12. Surat Municipal Institute of Medical Education &

Research, Surat

Dr. Sachendra Ku. Srivastava [email protected]/drarvi

[email protected]

13. M.P. Shah Medical College, Jamnagar Dr. Hiren R. Trivedi [email protected]/

[email protected]

14. PDU Medical College, Rajkot Dr. S. T. Hotchandani [email protected]















15. Haryana Medanta-The Medicity Sector-38, Gurgaon Dr. Himanshu Baweja [email protected]

16. PanditBhagwatDayal Sharma, Post Graduate

Institute of Medical Sciences, Rohtak

Dr MC Gupta [email protected]/

[email protected]

17. J&K

Govt. Medical College, Bakshi Nagar, Jammu Dr. Vishal Tandon [email protected]

18. Sher-i-Kashmir Institute of Medical Sciences,

Srinagar

Dr. ZA Wafai [email protected]

19. Jharkhand Rajendra Institute of Medical Sciences (RIMS),

Ranchi

Dr. Janardan Sharma [email protected]

20. Karnataka Bangalore Medical College and Research

Institute, Bengaluru

Dr. C. R. Jayanthi [email protected]

21. Belgaum Institute of Medical Sciences, Belgaum Dr. Basavaraj Kotintot [email protected]

22. Bidar Institute of Medical Sciences, Bidar Dr. B.O. Hanumanthappa [email protected]

23. JSS Medical College Hospital, Mysore Dr. Parthasarathi G [email protected]

24. Karnataka Institute OF Medical Sciences, Hubli Dr. Janaki. R. Torvi [email protected]/kims_hubl

[email protected]

25. Kasturba medical College, Manipal Dr. K. L. Bairy [email protected]/klbairy@yah

oo.com

26. Mandya Institute of Medical Sciences (MIMS),

District Hospital Campus, Mandya

Dr. Nagabushan

[email protected]

27. SDS Tuberculosis Research Centre & Rajiv

Gandhi Institute of Chest Disease, Bengaluru

Dr. Shashidhar Buggi [email protected]/direct

[email protected]

28. St. John’s Medical College, Bengaluru Dr. Padmini Devi [email protected]

29. Vijaynagar Institute of Medical Sciences, Bellary Dr. C. Lakshmi Narayana [email protected]/blydrkln

@gmail.com

30. Vydehi Institute of Medical Sciences and

Research Centre, Bengaluru

Dr. Pratibha Nadig [email protected]

31. Kerala Govt. Medical College Kozhikode Dr. P.V. Narayanan [email protected]

.in

32. Govt. Medical College, Kottayam Dr. Kala Kesavan [email protected]












mailto:[email protected]/





33. Pushpagiri Institute of Medical Sciences and

Research centre, Pushpagiri Medical College

Hospital, Tiruvalla

Dr. Santosh Pillai [email protected]

34. Madhya

Pradesh

Gandhi Medical College, Bhopal Dr. Arun Srivastav [email protected]

35. RD Gardi Medical College, Ujjain Dr. S.P. Dhaneria [email protected]

36. SAIMS Medical College, Indore Dr. Chhaya Goyal [email protected]

37. Maharashtra BJ Medical College & Sassoon General Hospital,

Pune

Dr. Pradeep Deshpande pradeepdeshpande.deshpande69@g

mail.com

38. Government Medical College & Hospital, Nagpur Dr. Ganesh N. Dakhle [email protected]/gndakhle

@rediffmail.com

39. Grant medical college & Sir JJ Group of Hospital,

Mumbai

Dr. S. B. Patel [email protected]/dr.sbpat

[email protected]

40. Indira Gandhi Government Medical College,

Nagpur

Dr. Vandana Avinash Badar [email protected],/am1

[email protected]

41. LokmanyaTilak municipal Medical College &

General Hospital, Mumbai

Dr. Sudhir R. Pawar [email protected]

42. Mahatma Gandhi Institute of Medical Sciences,

Nagpur

Dr. Sushil Kumar Varma [email protected]/varmasushil9

@gmail.com

43. MGM Medical College and Hospital, Kalamboli,

Navi Mumbai

Dr. Daniel Joseph [email protected]

44. Pd. Dr. D.Y. Patil Medical College, Pimpri, Pune Dr. P.S. Worlikar [email protected]

45. Seth GS Medical College & KEM Hospital, Parel,

Mumbai

Dr. Urmila Thatte [email protected]/urmilathatt

[email protected]

46. Swami Ramanand Teerth Rural Govt Medical

College, Ambajogai

Dr. V.M. Motghare [email protected]

47. TN Medical College &Byl Nair Hospital, Mumbai

Central, Mumbai

Dr. Renuka Kulkarni-Munshi [email protected]

48. Odisha VSS Medical College, Burla Dr. Sabita Mohapatra [email protected]

49. M. K. C. G Medical College, Berhampur Dr. Bandana Rath [email protected]

50. SCB Medical College and Hospital, Cuttack Dr. Srikanta Mohanty [email protected]/adr.sc

[email protected]/




















[email protected]

51. Punjab Christian Medical College and Hospital, Brown

Road, Ludhiana

Dr. Dinesh Kumar Badyal [email protected]

52. Dayanand Medical College and Hospital,

Ludhiana

Dr. Sandeep Kaushal [email protected]

53. Govt. Medical College Patiala Dr. Anita Gupta [email protected]

54. Rajasthan Sardar Patel Medical College, Bikaner Dr. Kiran Barar [email protected]/kiran

[email protected]

55. SMS Medical College, Jaipur

Dr. Mukul Mathur [email protected]/co

[email protected]

56. Sikkim Sikkim Manipal Institute of Medical Sciences,

Tadong, Gangtok

Dr. Supratim Datta [email protected]

57. Tamil Nadu Christian Medical College, Vellore Dr. Dr. J.V. peter peterjohnvictor @yahoo.com.au

58. Govt. Kilpauk Medical College, Chennai Dr. C. Ramachandra Bhat [email protected]

59. Madras Medical College, Chennai Dr. R Nandini [email protected]

60. PSG Institute of Medical Sciences & Research,

Coimbatore

Dr. S. Ramalingam [email protected]

61. SRM Medical College Hospital & Research

Centre, kattankulathur, Chennai

Dr. Jamuna Rani [email protected]

62. Tripura Agartala Govt. Medical College, Agartala Dr. Debasis Ray [email protected]

63. Tripura Medical College & Dr. BRAM Teaching

Hospitals, Hapania, Agartala

Dr. T.N. Sharma [email protected]

64. Uttar Pradesh B.R.D Medical College & Nehru Hospital,

Gorokhpur

Dr. P.P. Gupta [email protected]

65. GSVM Medical College, Swaroop Nagar, Kanpur Dr S.P. Singh [email protected]

66. Institute of Medical Sciences Banaras Hindu

University, Varanasi

Dr. B.L. Pandey [email protected]

67. JN Medical College Aligarh Muslim University ,

Aligarh

Dr. Mohammad Nasiruddin [email protected]

68. M.L.B. Medical College, Jhansi Dr.Sadhna Kaushik [email protected]

69. M.L.N Medical College, Allahabad Dr. Rakesh Chandra Chaurasia [email protected]






http://yahoo.com.au/












70. Santosh Medical University, Santosh Nagar,

Ghaziabad

Dr. VC Chopra [email protected]

71. U.P Rural Institute of Medical Sciences and

Research, Safai, Etwah

Dr. Asha Pathak [email protected]

72. Uttarakhand Govt Medical College, Haldwani Dr. Bhavana Srivastava [email protected]

73. Himalayan Institute of Medical Sciences,

Dehradun

Dr. DC Dhasmana [email protected]

74. Veer Chandra Singh Garhwali Medical Science

and Research Institute, Srinagar, Garhwal

Dr. Vijay Thawani [email protected]

om/[email protected]

75. West Bengal School of Tropical Medicine, Chittaranjan

Avenue, Kolkata

Dr. Santanu Tripathi [email protected]

76. R.G. Kar Medical College, Kolkatta Dr. Anjan Adhikari [email protected]

77. Calcutta National Medical College, Kolkata Dr. Syed Mohammad Naser [email protected]

78. Institute of Postgraduate Medical Education &

Research, Kolkata

Dr. Suparna Chatterjee [email protected]

79. Burdwan Medical college, Burdwan Dr. Swati Bhattacharyya [email protected]

80. BankuraSammilani Medical College, Bankura Dr. Santanu Munshi [email protected]/

[email protected]

81. NilratanSircar Medical College, Kolkata Prof. Nina Das [email protected]

82. Chandigarh PGIMER, Chandigarh Dr. Bikash Medhi [email protected]

83. Delhi All India Institute of Medical Sciences (AIIMS) Dr. Y.K. Gupta [email protected]/

[email protected]

84. Indraprastha Apollo Hospital Dr. Lalit Kanodia [email protected]

85. Lady Hardinge Medical College (LHMC) Dr. H.S. Rehan [email protected]

86. University College of Medical Sciences, Dilshad

Garden

Dr. S. K. Bhattacharya [email protected]

87. Vallabhbhai Patel Chest Institute (VPCI) -

University of Delhi

Dr. A. Ray [email protected]

88. VMMC &Safdarjung Hospital Dr. C.D. Tripathi [email protected]

















http://www.du.ac.in/index.php?id=463

http://www.du.ac.in/index.php?id=463




89. Puduchery Indira Gandhi Medical College & Research

Institute, Kadirkamam.

Dr. G. Sivagnanam [email protected]/adigaisc

[email protected]

90. JIPMER, Pondicherry Dr. C Adithan [email protected]





Annexure 2: Terminologies used in

Pharmacovigilance

Absolute risk

Risk in a population of exposed persons; the probability of an event affecting members of a

particular population (e.g. 1 in 1,000). Absolute risk can be measured over time (incidence)

or at a given time (prevalence).

Adverse event

Any untoward medical occurrence that may present during treatment with a pharmaceutical

product but which does not necessarily have a causal relationship with this treatment.

Adverse (drug) reaction (ADR)

A response which is noxious and unintended, and which occurs at doses normally used in

humans for the prophylaxis, diagnosis, or therapy of disease, or for the modification of

physiological function. (WHO, 1972).

An adverse drug reaction, contrary to an adverse event, is characterized by the suspicion of a

causal relationship between the drug and the occurrence, i.e. judged as being at least possibly

related to treatment by the reporting or a reviewing health professional.

Association

Events associated in time but not necessarily linked as cause and effect.

Attributable risk

Difference between the risk in an exposed population (absolute risk) and the risk in an

unexposed population (reference risk). Also referred to as excess risk.

Attributable risk is the result of an absolute comparison between outcome frequency

measurements, such as incidence.

Examples: If the exposed persons with a particular outcome are A, the exposed persons

without the outcome are B, the unexposed persons with the outcome are C and the unexposed

persons with the outcome are D, then the attributable risk is calculated as : [A / (A+B)] - [C /

(C+D)]. If, during the same time period, the incidence of rash in a population treated with



medicine X is 20/1,000=0.02, and the incidence of rash in a population not treated with X is

5/2,000=0.0025, the attributable risk is (20/1,000) - (5/2,000) = 0.0175.

Benefit

An estimated gain for an individual or a population. See also Effectiveness/Risk.

Benefit - risk analysis

Examination of the favourable (beneficial) and unfavourable results of undertaking a specific

course of action. (While this phrase is still commonly used, the more logical pairings of

benefit-harm and effectiveness-risk are slowly replacing it).

Biological products

Medical products prepared from biological material of human, animal or microbiologic origin

(such as blood products, vaccines, insulin).

Causal relationship

A relationship between one phenomenon or event (A) and another (B) in which A precedes

and causes B. In pharmacovigilance; a medicine causing an adverse reaction.

Causality assessment

The evaluation of the likelihood that a medicine was the causative agent of an observed

adverse reaction. Causality assessment is usually made according established algorithms.

CIOMS

The Council for International Organizations of Medical Sciences (CIOMS) is a body set up

under World Health Organization and UNESCO. It has developed a series of guidelines on

pharmacovigilance, drawn up by a committee of volunteers from Industry, regulatory

authorities, WHO and others.

The main guidelines concern the international reporting form (CIOMS I); periodic safety

update reports (CIOMS II); core data sheets (CIOMS III); benefit-risk assessments (CIOMS

IV); practical issues in pharmacovigilance (CIOMS V); clinical trial safety data (CIOMS VI);

and development safety update reports (CIOMS VII).



Clinical trial

A systematic study on pharmaceutical products in human subjects (including patients and

other volunteers) in order to discover or verify the effects of and/or identify any adverse

reaction to investigational products, and/or to study the absorption, distribution, metabolism

and excretion of the products with the objective of ascertaining their efficacy and safety.

Cohort Event Monitoring

Cohort Event Monitoring (CEM) is a prospective, observational study of events that occur

during the use of medicines, for intensified follow-up of selected medicinal products phase.

Patients are monitored from the time they begin treatment, and for a defined period of time.

See also Prescription Event Monitoring.

Common Epidemiology

In pharmacovigilance, an event with a frequency between 1 in 100 and 1 in 10.

Co-morbidities

Two or more coexisting medical conditions or disease processes that are additional to an

initial diagnosis.

Compliance

Faithful adherence by the patient to the prescriber's instructions.

Congenital Anomalies

Morphological, functional and/or biochemical developmental disturbance in the embryo or

foetus whether detected at birth or not. The term congenital anomaly is broad and includes

congenital abnormalities, foetopathies, genetic diseases with early onset, developmental

delay, etc.

Control group

The comparison group in drug-trials not being given the studied drug.

Critical terms

Some of the terms in WHO-ART are marked as "Critical Terms". These terms either refer to

or might be indicative of serious disease states, and warrant special attention, because of their



possible association with the risk of serious illness which may lead to more decisive action

than reports on other terms.

Data-mining

At the UMC, the use of an automated tool, based on Bayesian logic, for the scanning of the

WHO database (VigiBase) in the process of detecting drug-adverse reaction associations: the

BCPNN. Knowledge-detection is the preferred term for the process.

De-challenge

The withdrawal of a drug from a patient; the point at which the continuity, reduction or

disappearance of adverse effects may be observed.

Disproportionality analysis

Screening of ICSR databases for reporting rates which are higher than expected. For drug-

ADR pairs, common measures of disproportionality are the Proportional Reporting Ratio

(PRR), the Reporting Odds Ratio (ROR), The Information Component (IC), and the

Empirical Bayes Geometrical Mean (EBGM). There are also disproportionality measures for

drug-drug-ADR triplets, such as Omega (Ω).

Drug Abuse

It is a patterned use of a drug in which the user consumes the substance in amounts or with

methods neither approved nor supervised by medical professionals.

Effectiveness/risk

The balance between the rate of effectiveness of a medicine versus the risk of harm is a

quantitative assessment of the merit of a medicine used in routine clinical practice.

Comparative information between therapies is most useful. This is more useful than the

efficacy and hazard predictions from pre-marketing information that is limited and based on

selected subjects.

Efficacy

The ability of a drug to produce the intended effect as determined by scientific methods, for

example in pre-clinical research conditions (opposite of hazard).



Epidemiology

The science concerned with the study of the factors determining and influencing the

frequency and distribution of disease, injury and other health-related events and their causes

in a defined human population for the purpose of establishing programs to prevent and

control their development and spread (Dorland's Illustrated Medical Dictionary).

Essential medicines

Essential medicines are those that satisfy the priority health care needs of the population.

They are selected with due regard to public health relevance, evidence on efficacy and safety,

and comparative cost-effectiveness.

EVMPD

The EudraVigilance Medicinal Product Dictionary (EVMPD) has been developed by the

European Medicines Agency in collaboration with the EudraVigilance Joint Implementation

Group. The main objective of the EVMPD is to assist the pharmacovigilance activities in the

European Economic Area.

EUDRAGENE

Eudragene is a European collaboration that established a collection of DNA samples as a

resource for studying genes which influence serious or adverse drug reactions (ADRs).

Identifying genes that influence susceptibility to adverse reactions will advance

understanding of the basis of adverse drug reactions and may also lead to the development of

tests that can predict individual susceptibility to adverse reactions.

Excipients

All materials included to make a pharmaceutical formulation (e.g. a tablet) except the active

drug substance(s).

Formulary

A listing of medicinal drugs with their uses, methods of administration, available dose forms,

side effects, etc., sometimes including their formulas and methods of preparation.



Generic (multisource product)

The term "generic product" has somewhat different meanings in different jurisdictions.

Generic products may be marketed either under the non-proprietary approved name or under

a new brand (proprietary) name. They are usually intended to be interchangeable with the

innovator product, which is usually manufactured without a license from the innovator

company and marketed after the expiry of patent or other exclusivity rights.

Harm

The nature and extent of actual damage that could be caused by a drug. Not to be confused

with risk.

ICH

The International Conference on Harmonization of Technical Requirements for the

Registration of Pharmaceuticals.

ICD

International Classification of Diseases (ICD) is the standard diagnostic tool for

epidemiology, health management and clinical purposes.

Incidence

The extent or rate of occurrence, especially the number of new cases of a disease in a

population over a period of time.

Individual Case Safety Report

A report that contains information describing a suspected adverse drug reaction related to the

administration of one or more medicinal products to an individual patient.

MedDRA

MedDRA or Medical Dictionary for Regulatory Activities is a clinically-validated

international medical terminology used by regulatory authorities and the regulated

biopharmaceutical industry. The terminology is used through the entire regulatory process,

from pre-marketing to post-marketing, and for data entry, retrieval, evaluation, and

presentation.



Medical error

"An unintended act (either of omission or commission) or one that does not achieve its

intended outcomes." Leape, Lucien. Error in Medicine. Journal of the American Medical

Association 272(23):1851-57 (Dec. 21, 1994).

Over the counter (OTC)

Medicines which are available for purchase without prescription.

Off-label-use

When the medicinal product is intentionally used for a medical purpose not in accordance

with the authorised product information.

Overdose

Administration of a quantity of a medicinal product given per administration or cumulatively,

which is above the maximum recommended dose according to the authorised product

information.

Pharmacoepidemiology

Study of the use and effects of drugs in large populations.

Pharmacology

Pharmacology is the science of drugs (Greek: Pharmacon-drug; logos-discourse in) . In a

broad sense, it deals with interaction of exogenously administered chemical molecules

(drugs) with living systems. It encompasses all aspects of knowledge about drugs, but most

importantly those that are relevant to effective and safe use for medicinal purposes.

Pharmacovigilance

The science and activities relating to the detection, assessment, understanding and prevention

of adverse effects or any other drug-related problem.

Phocomelia

Characteristic deformity caused by exposure to thalidomide in the womb, also very rarely

occurring spontaneously. Meaning: limbs like a seal.



Placebo

An inactive substance (often called a sugar pill) given to a group being studied to compare

results with the effects of the active drug.

Polypharmacy

The concomitant use of more than one drug, sometimes prescribed by different practitioners.

Post-authorization safety study (PASS)

A pharmacoepidemiological study or a clinical trial carried out in accordance with the terms

of the Marketing Authorisation, with the aim of identifying or quantifying a safety hazard

relating to an authorized medicinal product.

Post-marketing

The stage when a drug is generally available on the market.

Predisposing factors

Any aspect of the patient’s history (other than the drug) which might explain reported adverse

events (for example, genetic factors, diet, alcohol consumption, disease history,

polypharmacy or use of herbal medicines).

Pre-marketing

The stage before a drug is available for prescription or sale to the public.

Prescription event monitoring (PEM)

System created to monitor adverse drug events in a population. Prescribers are requested to

report all events, regardless of whether they are suspected adverse events, for identified

patients receiving a specified drug. Also more accurately named "cohort-event monitoring".

Prescription only medicine (POM)

Medicinal product available to the public only on prescription.

Prophylaxis

Prevention or protection.



PSUR

The Periodic Safety Update Report (PSUR) is a stand-alone document that allows a periodic

but comprehensive assessment of the worldwide safety data of a marketed drug or biological

product.

QPPV

Qualified Person responsible for Pharmacovigilance.

Rare

In pharmacovigilance an event with a probability between 1 in 10,000 and 1 in 1,000.

Rational drug use

An ideal of therapeutic practice in which drugs are prescribed and used in exact accordance

with the best understanding of their appropriateness for the indication and the particular

patient, and of their benefit, harm effectiveness and risk.

Re-challenge

The point at which a drug is again given to a patient after its previous withdrawal (see de-

challenge).

Reference risk

Risk in a population of unexposed persons. Also called baseline risk. Reference risk can be

measured over time (incidence) or at a given time (prevalence). The unexposed population

refers to a reference population, as closely comparable to the exposed population as possible,

apart from the exposure.

Regulatory authority

The legal authority in any country with the responsibility of regulating all matters relating to

drugs.

Relative risk

Ratio of the risk in an exposed population (absolute risk) and the risk in an unexposed

population (reference risk). Relative risk is the result of a relative comparison between

outcome frequency measurements, e.g. incidences.



Example: If the exposed persons with an outcome are A, the exposed persons without the

outcome are B, the unexposed persons with the outcome are C, and the unexposed persons

without the outcome are D, the relative risk is calculated as [A / (A+B)] / [C / (C+D)].

If the incidence of rash in a population treated with medicine X is 35/1,500=0.023, and the

incidence of rash in a population which is not treated with X, during the same time period, is

5/2,000=0.0025, the relative risk is (35/1,500) / (5/2,000) = 9.3.

Risk

The probability of harm being caused; the probability (chance, odds) of an occurrence.

SAEC

The International Serious Adverse Events Consortium (SAEC) is a non-profit consortium

formed in October 2007 between industry, academia, the Wellcome Trust, and the US Food

and Drug Administration to identify genetic variants associated with serious adverse events.

Serious Adverse Event or Reaction

A serious adverse event or reaction is any untoward medical occurrence that at any dose:

results in death

results in life-threatening condition

requires inpatient hospitalization or prolongation of existing hospitalization

results in persistent or significant disability/incapacity

causes congenital abnormality

requires any intervention to prevent the occurrence of any of the above

To ensure no confusion or misunderstanding of the difference between the terms "serious"

and "severe", the following note of clarification is provided:

The term "severe" is not synonymous with serious. In the English language, "severe" is used

to describe the intensity (severity) of a specific event (as in mild, moderate or severe); the

event itself, however, may be of relatively minor medical significance (such as severe

headache). Seriousness (not severity) which is based on patient/event outcome or action

criteria serves as guide for defining regulatory reporting obligations.



Side effect

Any unintended effect of a pharmaceutical product occurring at normal dosage which is

related to the pharmacological properties of the drug.

Signal

Reported information on a possible causal relationship between an adverse event and a drug,

the relationship being unknown or incompletely documented previously. Usually more than a

single report is required to generate a signal, depending upon the seriousness of the event and

the quality of the information. The publication of a signal usually implies the need for some

kind of review or action.

Spontaneous reporting

System whereby case reports of adverse drug events are voluntarily submitted from health

professionals and pharmaceutical manufacturers to the national regulatory authority.

SUSAR (Suspected Unexpected Serious Adverse Drug Reaction)

A serious adverse drug reaction whose nature, severity or frequency is not identified

previously in the risk information provided to the clinical investigator’s brochure (CIB) or on

the drug label.

Summary of Product Characteristics

A regulatory document attached to the marketing authorization which forms the basis of the

product information made available to prescribers and patients.

Teratogen

Environmental factors which can cause congenital abnormalities.

Traditional Medicines

Traditional medicine is the sum total of the knowledge, skills, and practices based on the

theories, beliefs, and experiences indigenous to different cultures, whether explicable or not,

used in the maintenance of health as well as in the prevention, diagnosis, improvement or

treatment of physical and mental illness.

Uncommon

In pharmacovigilance an event with a frequency between 1 in 1.000 and 1 in 100.



Unexpected adverse reaction

An adverse reaction, the nature or severity of which is not consistent with domestic labeling

or market authorization, or expected from characteristics of the drug.

VigiBase

The name of the WHO Global ICSR Database.

WHO-ART

Terminology for coding clinical information in relation to drug therapy. WHO-ART is

maintained by UMC.

WHO Drug Dictionary (WHO-DD)

The WHO Drug Dictionary is an international classification of drugs providing proprietary

and on-proprietary names of medicinal products used in different countries, together with all

active ingredients.



Annexure 3: Organisations, societies, regulators &

useful websites

1. The Central Drugs Standard Control Organisation Headquarters

CDSCO is the national regulatory body for Indian pharmaceuticals and medical devices, and

serves parallel function to the European Medicines Agency of the European Union,

the PMDA of Japan and the Food and Drug Administration of the United States. Within the

CDSCO, the DCG (I) regulates pharmaceutical and medical devices. The DCGI is advised by

the Drug Technical Advisory Board (DTAB) and the Drug Consultative Committee (DCC). It

is divided into zonal offices which do pre-licensing and post-licensing inspections, post-

market surveillance, and recalls when needed.

Official website: www.cdsco.nic.in

2. Indian Pharmacopoeia Commission

IPC is an autonomous institution of the Ministry of Health and Family Welfare, Government

of India. IPC is created to set standards of drugs in the country. Its basic function is to update

regularly the standards of drugs commonly required for treatment of diseases prevailing in

this region. It publishes official documents for improving quality of medicines by way of

adding new and updating existing monographs in the form of IP. It further promotes rational

use of generic medicines by publishing NFI. IPC also acts as a NCC for PvPI, thereby

coordinating all the activities related to PV in India.

Official website: www.ipc.gov.in

3. WHO Collaborating Centre for International Drug Monitoring: The Uppsala

Monitoring Centre

The WHO is a specialized agency of the UN that is concerned with international public

health. The UMC is an independent foundation and a centre for international service and

scientific research.

The operational responsibility for the ADR monitoring programme rests with the WHO

Collaborating Centre for International Drug Monitoring, UMC, in Sweden. The system

started with 10 countries that had already established national systems for spontaneous

adverse reaction reporting and who agreed to contribute data. For an effective international

http://www.cdsco.nic.in/

3introduction%20to%20pharmacovigilance.docx

3introduction%20to%20pharmacovigilance.docx



system to become operative, a common reporting form was developed, agreed guidelines for

entering information formulated, common terminologies and classifications prepared and

compatible systems for transmitting, storing and retrieving and disseminating data were

created. The ADRs database in Uppsala currently contains over eight million reports of

suspected ADRs.

Official website: www.who-umc.org

4. WHO Country office for India

Envisioning better health for all Indians, Mr Ghulam Nabi Azad, Hon’ble Minister for Health

& Family Welfare, Government of India launched WHO’s new Country Cooperation Strategy

(CCS), 2012-17with India along with Dr Nata Menabde, WHO representative to India on 29

June 2012. The WHO Country Office for India is headquartered in Delhi with country-wide

presence. Its areas of work are enshrined in its new CCS, 2012-2017.The key aim of this path-

breaking strategy is to contribute to improving health and equity in India. It also provides the

blueprint for unleashing India’s role on the global health arena alongside the continued pursuit

of health improvement in the country. In this context, it distinguishes and addresses the

challenges to India’s potential globally as well as impediments in solving long-standing health

and health service delivery internally.

The WHO Country Office for India also coordinates pharmacovigilance training programmes

to the PV professionals, preparation and updating of PV toolkit and other regulatory

documents for PvPI.

Official website: www.whoindia.org

5. National Institute of Biologicals

National Institute of Biologicals is an autonomous institution under the MoHFW,

Government of India and is a premier scientific organization and a centre of excellence to

ensure quality of biological and vaccines in the country. The institute responsibly assures

and reviews the quality of number of biological products available through domestic

manufacturers or imports. The operations are carried out in the state of the art facility of the

institute and in close coordination with regulatory authorities.

Official website: www.nib.gov.in

http://www.who-umc.org/

http://www.whoindia.org/

http://www.nib.gov.in/



6. International Conference on Harmonization of Technical Requirements

for Registration of Pharmaceuticals for Human Use (ICH)

ICH is a project that brings together the regulatory authorities of Europe, Japan and the

United States and experts from the pharmaceutical industry in the three regions to discuss

scientific and technical aspects of pharmaceutical product registration.

Official website: www.ich.org

http://www.ich.org/



Annexure 4: Literature resources for

pharmacovigilance

Following literature resources can provides further information to NCC and AMCs under

PvPI, regarding drug safety monitoring and other aspects of pharmacovigilance.

Books

1. Alesso, L. (2007) Farmacovigilancia: HaciaUna Mayor Seguridad en el Uso de

Medicamentos, Los talleresgráficos de Alejandro Graziani S.A. (2nd edition planned)

2. Aronson, JK. (ed.) (2006) Meyler's Side Effects of Drugs, 15th

edition, Elsevier

Science.

3. Aronson, JK. (ed.) (2010) Side Effects of Drugs Annual (36), Elsevier.

4. Baxter, K. (ed.) (2010) Stockley's Drug Interactions, 9th edition, Pharmaceutical Press.

5. Begaud, B. (2000) Dictionary of Pharmacoepidemiology, John Wiley & Sons Ltd.

6. Bennett, P., Calman, K., Curtis, S. and Fischbacher-Smith, D. (2010) Risk

Communication and Public Health, 2nd edition, Oxford University Press, USA.

7. BMJ. (2007) Clinical Evidence Handbook: The International Source of the Best

Available Evidence for Effective Healthcare, BMJ Publishing Group.

8. CIOMS. (1999) Benefit-Risk Balance for Marketed Drugs: Evaluating Safety

Signals (Report of CIOMS Working Group IV), WHO.

9. CIOMS. (2010) Practical Aspects of Signal Detection in Pharmacovigilance (Report

of CIOMS Working Group VIII), WHO.

10. Cobert, B. (2011) Cobert’s Manual of Drug Safety and Pharmacovigilance,

2nd

edition, Jones & Bartlett Learning.

11. Cobert, B. and Biron, P. (2008) Practical Drug Safety from A to Z, Jones & Bartlett

Publishers.

12. Cohen, MR. (2006) Medication Errors, 2nd edition, American Pharmacists

Association.

13. Dukes, G., Mildred, M. and Swartz, B. (1998) Responsibility for Drug-Induced Injury:

A Reference Book for Lawyers, the Health Professions and Manufacturers, IOS Press.

14. Gupta, SK. (ed.) (2011) Textbook of Pharmacovigilance, Jaypee Brothers Medical

Publishers (P) Ltd.

15. Hugman, B. (2009) Healthcare Communication, Pharmaceutical Press.

http://www.adlibris.com/se/product.aspx?isbn=0471803618



16. Klepper, MJ. andCobert, B. (2010) Drug Safety Data: How to Analyze, Summarize,

and Interpret to Determine Risk, Jones & Bartlett Learning.

17. Klincewicz, SL., Yap, YY., Thomas, A. with Taylor, JL. (ed.) (2009) Global

Pharmacovigilance: Laws & Regulations, the Food and Drug Law Institute.

18. Mann, RD. and Andrews, EB. (ed.) (2007) Pharmacovigilance, 2nd edition, John

Wiley & Sons Ltd.

19. MHRA. (2008) Good Pharmacovigilance Practice Guide, Pharmaceutical Press.

20. Slovic, P. (2000) The Perception of Risk, Earthscan Publications Ltd.

21. Strom, BL. (2005) Pharmacoepidemiology, 4th edition, John Wiley & Sons Ltd.

22. Sweetman, SC. (ed.)(2011) Martindale: The Complete Drug Reference, 37th edition,

Pharmaceutical Press.

23. Talbot, J. and Waller, P. (ed.) (2003) Stephen’s Detection of New Adverse Drug

Reactions, 5th edition, John Wiley & Sons Ltd.

24. Van Boxtel, CJ.,Santoso, B. and Edwards, IR. (ed.) (2008) Drug Benefits and Risks:

International Textbook of Clinical Pharmacology, 2nd edition, IOS Press.

25. Vincent, C. (2010) Patient Safety, 2nd edition, Wiley-Blackwell.

26. Waller, P. (2009) An Introduction to Pharmacovigilance, Wiley-Blackwell.

Journals

1. ADR Newsletters from National Centres

2. BMJ (British Medical Journal)

3. Drug Information Journal

4. Drug Safety

5. Indian Heart Journal

6. Indian Journal of Pathology & Microbiology

7. Indian Journal of Cancer

8. Indian Journal of Clinical Medicine

9. Indian Journal of Dentistry

10. Indian Journal of Dermatology

11. Indian Journal of Gastroenterology

12. Indian Journal of Health & Wellbeing

13. Indian Journal of Medicine

14. Indian Journal of Oncology & Radiation Biology

http://www.who-umc.org/DynPage.aspx?id=102898&mn1=7347&mn2=7261&mn3=7478

http://www.bmj.com/

http://www.bmj.com/

http://www.diahome.org/en/Resources/Publications/JournalsandMagazines

http://adisonline.com/drugsafety/pages/default.aspx



15. Indian Journal of Ophthalmology

16. Indian Journal of Pharmaceutical Sciences

17. Indian Journal of Pharmacology

18. Indian Journal of Pharmacy Practice

19. Indian Journal of Psychiatry

20. Indian Journal of Public Health

21. Indian Journal of Sexually Transmitted Diseases and AIDS

22. Indian Journal of Transfusion Medicine

23. JAMA (Journal of the American Medical Association)

24. Journal of Indian Medical Association

25. Pharmacoepidemiology & Drug Safety

26. Pharmacoepidemiology and Drug Safety

27. Prescrire

28. Reactions Weekly

29. The Indian Journal of Hospital Pharmacy

30. The Indian Journal of Medical Research

31. The Indian Journal of Paediatrics

32. The International Journal of Risk & Safety in Medicine

33. The Journal of Family Welfare

34. The Lancet

35. The New England Journal of Medicine

36. The Nursing Journal of India

Publications

1. PvPI Newsletters

2. Safer Medicines, Safer Use of Medicines, Safer Patients (leaflet)

3. Aide Memoire - For a National Strategy for Safe Drugs and Their Appropriate Use

4. WHO Policy Perspectives on Medicines no. 9 - PV: Ensuring the Safe Use of

Medicines

5. Viewpoint (part 1)

6. Viewpoint (part 2)

7. The Importance of Pharmacovigilance - Safety Monitoring of Medicinal Products

http://www.jama.ama-assn.org/

http://www.jama.ama-assn.org/

http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1099-1557

http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291099-1557/issues

http://english.prescrire.org/en/

http://adisonline.com/reactions/pages/default.aspx

http://iospress.metapress.com/content/103162/

http://www.thelancet.com/

http://www.nejm.org/

http://www.who.int/medicinedocs/en/d/Js6164e/#Js6164e

http://www.who.int/medicinedocs/en/d/Js6164e/#Js6164e

http://www.who-umc.org/graphics/24744.pdf


http://www.who.int/medicinedocs/en/d/Js4893e/



8. Safety Monitoring - Guidelines for Setting Up and Running a Pharmacovigilance

Centre

9. Safety of Medicines - A Guide to Detecting and Reporting Adverse Drug Reactions

10. Being a Member of the WHO Programme

11. Uppsala Reports (Newsletter)

12. Vigiflow - when time is crucial (leaflet)

13. VigiSearch/VigiMine (leaflet)

14. CemFlow (leaflet)

15. SIGNAL

16. WHO Pharmaceuticals Newsletter

17. WHO Drug Information

18. WHO: Pharmaceuticals: Restrictions in Use and Availability

19. Effective Communications in Pharmacovigilance - The Erice Report

20. Dialogue in Pharmacovigilance - More Effective Communication

21. Expecting the Worst (2nd Edition 2010)

22. The Safety of Medicines in Public Health Programmes - Pharmacovigilance an

Essential Tool

23. A Practical Handbook on the Pharmacovigilance of Antimalarial Medicines

24. A Practical Handbook on the Pharmacovigilance of Antiretroviral Medicines

25. WHO Guidelines on Safety Monitoring of Herbal Medicines

26. Accepted Scientific Names of Therapeutic Plants and their Synonyms

27. Herbal ATC Guide

28. Writings on Pharmacovigilance - Selected articles by David J Finney

29. A Lifetime in Safety - Selected articles by Ed Napke

30. Promoting Safety of Medicines for Children

31. The world medicines situation 2011 –Pharmacovigilance and safety of medicines

http://www.who-umc.org/DynPage.aspx?id=105828&mn1=7347&mn2=7259&mn3=7297&mn4=7496


http://www.who.int/medicinedocs/en/d/Jh2992e/



http://www.who.int/medicines/publications/newsletter/en/

http://www.who.int/medicines/publications/druginformation/en

http://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharm_restrictions/en




http://www.who.int/entity/medicines/areas/quality_safety/safety_efficacy/Pharmacovigilance_B.pdf

http://www.who.int/entity/medicines/areas/quality_safety/safety_efficacy/Pharmacovigilance_B.pdf

http://www.who.int/entity/medicines/technical_briefing/tbs/handbook_antimalarialpharmvigilance.pdf

http://www.who.int/medicines/areas/quality_safety/safety_efficacy/HIVhandbook.pdf






http://www.who.int/medicinedocs/index/assoc/s14235e/s14235e.pdf

http://apps.who.int/medicinedocs/documents/s18771en/s18771en.pdf