GUIDELINES FOR MONITORING AND REPORTING ADVERSE DRUG

REACTIONS
For Healthcare professionals & Patients

NATIONAL MEDICINES REGULATORY AUTHORITY

NORIS CANAL ROAD, COLOMBO 10, SRI LANKA

Preface
Patients expect the medicines they receive to be safe and effective. Healthcare professionals
expect the medicines they prescribe, dispense or administer are potentially safe. Safety of
medicinal products is the primary concern of any Medicines Regulatory Body in the world.
Although the duties, responsibilities and scopes of these different parties may be different
invariably the objective of safety remains comparable. Being vigilance on medicinal product is
an integral element towards assurance of the safety of medicinal products.

Success of any pharmacovigilance system depends on the receipt of the reports and the
subsequent procedures. This document provides guidance to all healthcare institutes and
individuals as well as the patients who submit reports about their role and the good practices in
detection & reporting of adverse drugs reactions.

1
Contents
ABBREVIATIONS .......................................................................................................................................... 3
GLOSSARY OF TERMINOLOGY..................................................................................................................... 4
Introduction ............................................................................................................................................. 6
The need for pharmacovigilance ............................................................................................................. 6
Objectives of Pharmacovigilance ............................................................................................................. 7
WHO Programme for International Drug Monitoring.............................................................................. 7
The Scope of Pharmacovigilance ............................................................................................................. 8
Classification of adverse drug reactions ................................................................................................ 10
The National Pharmacovigilance system in Sri Lanka .............................................................................. 12
Approaches for medicines safety surveillance....................................................................................... 12
National reporting system ..................................................................................................................... 13
Information needed for adverse reaction reporting ............................................................................. 13
Seriousness of Adverse drug reactions .................................................................................................. 14
Unexpected Adverse Reaction ............................................................................................................... 15
Priorities for reporting ........................................................................................................................... 15
Black triangle scheme (intensified spontaneous reporting) .................................................................. 16
How to recognize ADRs in patients ........................................................................................................ 16
Who can report? .................................................................................................................................... 17
How to report ........................................................................................................................................ 17
Timelines for reporting .......................................................................................................................... 18
Reporting Follow up information........................................................................................................... 19
Will reporting have any negative consequences on the reporter?........................................................ 19
What are the benefits of reporting on Healthcare professionals and patients? ................................... 19
What Happens after reporting ADRs ..................................................................................................... 20
Taking regulatory action to minimize risk .............................................................................................. 21
Safety and Risk Evaluation Sub Committee (SAFRESC) .......................................................................... 22
Pharmacovigilance and the role of pharmaceutical companies ............................................................ 22
Pharmacovigilance in Public Health Programmes ................................................................................. 22
APPENDIX: ADR REPORTING FORMS ....................................................................................................... 24
APPENDIX: ANAPHYLAXIS REPORTING FORMS ....................................................................................... 25
APPENDIX: ADR Electronic Reporting ...................................................................................................... 27
References ................................................................................................................................................. 30

2
ABBREVIATIONS
ADRs - Adverse Drug Reactions

CEO - Chief Executive Officer

ICSR - Individual Case Safety Report

MEC - Medicines Evaluation Committee

MSD – Medical Supplies Division

NMQAL - National Medicines Quality Assurance Laboratory

NMRA - National Medicines Regulatory Authority

PV division – Pharmacovigilance Division

SAFRESC- Safety and Risk Evaluation Sub Committee

UMC - Uppsala Monitoring Centre

WHO - World Health Organization

WHO-ART - WHO Adverse Reaction Terminology

3
GLOSSARY OF TERMINOLOGY
Adverse Event:
Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal
product and which does not necessarily have a causal relationship with this treatment.

Adverse Reaction:
A response to a medicinal product which is noxious and unintended. Response in this context
means that a causal relationship between a medicinal product and an adverse event is at least a
reasonable possibility. Adverse reactions may arise from use of the product within or outside
the terms of the marketing authorization or from occupational exposure. Conditions of use
outside the marketing authorization include off-label use, overdose, misuse, abuse and
medication errors.

Causality Assessment
The evaluation of the likelihood that a medicine was the causative agent of an observed
adverse event in a specific individual. Causality assessment is usually made according to
established algorithms.

Individual Case Safety Report (ICSR)

A document providing the most complete information related to an individual case at a certain
point of time. An individual case is the information provided by a primary source to describe
suspected adverse reaction(s) related to the administration of one or more medicinal products
to an individual patient at a particular point of time.

Quality Failure
Any deviation of a genuine medicine authorized by the National Medicines Regulatory
Authority, from the quality specifications set for them by national standards.

Serious Adverse Event:

A serious adverse event (experience) or reaction is any untoward medical occurrence that at
any dose

• results in death;
• is life-threatening;

4
 • requires inpatient hospitalization or prolongation of hospitalization;
• results in persistent or significant disability/incapacity;
• is causing congenital anomaly/birth defect;
• Important medical events that may not be immediately life-threatening or result in
death or hospitalization but may jeopardize the patient or may require intervention to
prevent one of the other outcomes listed in the definition above. Medical and scientific
judgment should be exercised in these events

Unexpected Adverse Reaction

An adverse reaction, the nature or severity of which is not consistent with the applicable
product information (e.g., Investigator’s Brochure for an unapproved investigational product or
package insert/summary of product characteristics for an approved product). i.e. expected and
unexpected ADR can refer to labeled vs unlabeled (for official data sheets/package inserts for
marketed products)

Signal:

Information that arises from one or multiple sources (including observations and experiments),
which suggests a new potentially causal association or a new aspect of a known association,
between a medicine and an event or set of related events.

5
Introduction
National Medicines Regulatory Authority Act No. 05 of 2015 and rules and regulations thereof
provide legal provisions for pharmacovigilance in Sri Lanka. Pharmacovigilance, as defined by
the WHO is “the science and activities related to the detection, assessment, understanding and
prevention of adverse drug effects or any other possible drug-related problems. Furthermore,
adverse drug reaction is defined as a response which is noxious and unintended.

Underlying objectives of our pharmacovigilance system is preventing harm from adverse

reactions or any other drug related problems and promoting the safe and effective medicines in
particular through providing timely information about the safety of medicines to patients,
healthcare professionals and general public.

Ultimate objective of Pharmacovigilance is therefore safety of medicines.

Of late number of New Chemical Entities and Similar Bio Therapeutic Products that received
market authorization in Sri Lanka has been significantly increased. Due to the policy of the
government to encourage local manufacturing of pharmaceuticals considerable number of new
manufacturers has emerged within the Island. In this scenario strengthening Pharmacovigilance
system in Sri Lanka has been a timely necessity.

The need for pharmacovigilance

The information collected during the pre-marketing phase of medicines development is
inevitably incomplete with regard to possible ADRs. This is mainly because:

• Tests in animals are insufficient to predict human safety;

• Patients used in clinical trials are selected and limited in number, the conditions of use
differ from those in clinical practice and the duration of trials is limited;
• By the time of medicine licensing, exposure of less than 5000 human subjects to a
medicine allows only the more common ADR to be detected; while at least 30,000
people need to be treated with a medicine to be sure that you do not miss at least one
patient with an ADR which has an incidence of 1 in 10,000 exposed individuals;
• Information about rare but serious adverse reactions, chronic toxicity, use in special
groups (such as children, the elderly or pregnant women) or drug interactions is often
incomplete or not available

Thus, continuous safety monitoring of medicines which is the main objective of

pharmacovigilance is important to permit detection of less common, but sometimes very
serious ADRs. Therefore, health professionals and patients worldwide should report on
ADRs as it can save lives of their patients and others.

6
Objectives of Pharmacovigilance
In addition to the beneficial therapeutic outcomes that medicines can have, they can also cause
harm to patients. The pharmacovigilance can help to reduce this harm and support safer and
more effective use of medicines for everyone by:
1. Early detection and investigation of previously unknown adverse reactions or any other
medicines related problems
2. Recognition and investigation of the increases in frequency or any new aspects of
already known adverse reaction
3. Generate new hypothesis on ADRs that are specific to the local population
4. Quantitative analysis of benefit/risk ratio
5. Dissemination of information on ADRs and safe use of medicines for rational prescribing
and regulations
6. Identifying problems with batches or brands of medicines
7. Encouraging safe and rational use of medicines, including cost-effectiveness.

WHO Programme for International Drug Monitoring

The World Health Organization (WHO) Programme for International Drug Monitoring (PIDM)
was established in 1968 in response to the thalidomide disaster in which thousands of infants
were born with congenital deformations following fetal exposure to thalidomide, a medicine
that had been used to treat morning sickness in pregnancy. Initially a pilot project in 10
countries with established national reporting systems for ADRs, the network has since
expanded significantly as more countries worldwide developed national Pharmacovigilance
centers.

The PIDM provides a forum for WHO member states to collaborate in the monitoring of
medicines safety, and notably, the identification and analysis of new adverse reaction signals
from data submitted to the WHO global individual case safety report (ICSR) database by
member countries, Vigibase.

The programme consists of a three-part network:

• National Pharmacovigilance Centers (usually base in the regulatory authorities) from

WHO member countries are responsible for the running national pharmacovigilance
system, collecting, analyzing and sending national case reports to the WHO global
database;
• Uppsala Monitoring Center (UMC) oversees the WHO programme operations, including:
- maintaining the global Individual Case Safety Reports (ICSRs) database, Vigibase

7
 - collecting, assessing and communicating information from member countries
about the benefits, harm, effectiveness and risks of medicines;
- collaborating with member countries in the development and practice of
pharmacovigilance;
- alerting NMRAs of member countries about potential medicines safety problems
via the WHO signal process.
• WHO headquarters in Geneva, Switzerland is responsible for policy issues.

The Scope of Pharmacovigilance

Since the start of pharmacovigilance practice and over time, globally the pharmacovigilance
focus has shifted from the medicines to the patient and the scope of pharmacovigilance has
been extended regarding the following:

• Use of Medicines scope of pharmacovigilance include the monitoring of safety problems or

adverse effects related to the use of medicines whether used within or outside the terms of
the marketing authorization or from occupational exposure. Conditions of use outside the
marketing authorization include off-label use, overdose, misuse, abuse and medication
errors, as highlighted below:
- Adverse drug reaction (ADR) is a response to a medicinal product which is noxious and
unintended. Response in this context means that a causal relationship between a
medicinal product and an adverse event is at least a reasonable possibility
- Medication error is an unintended failure in the drug treatment process that leads to, or
has the potential to lead to, harm to the patient. For example, a medicine could be
wrongly prescribed by a doctor, wrongly dispensed by a pharmacist or nurse, or
administered incorrectly by a patient. Since most medication errors are a result of
system failures, for example lack of staff resulting in a heavy workload, that is why
reporting culture in Sri Lanka ensure that individuals are not blamed and punished, but
instead focus to identify the underlying causes and take proper action to prevent the
same error from happening again.

- Drug interaction occurs when the effects of one medicine are changed in the presence
of another drug, food or drink. Resulting in making the medicine more or less effective.
Although many interactions are well known, irrational combinations are still prescribed,
causing unwanted side effects. Many patients, especially the elderly, may take several

8
 medicines each day. Obviously, the risk of developing an undesired drug interaction
increases with the number of medicines used.

- Off-label use means situations where a medicinal product is intentionally used for a
medical purpose not in accordance with the terms of the marketing authorization. For
example, when a different indication, route of administration or dosage is used, or when
a medicine is used in a different age group. Previously, children were usually excluded
from clinical trials resulting in a lack of data and the need for special dosage
adjustments. New legislation has increased the number of medicines licensed for
pediatric use, but there is still room for improvement.

- Abuse, misuse and related events is when a medicinal product is intentionally used in a
manner that deviates from the prescribed pattern, which can have serious medical
consequences. The morbidity and mortality associated with non-therapeutic use of
medicines are rising and there is a need to implement strategies to cope with this
growing health problem.

- Overdose
This refers to the administration of a quantity of a medicinal product given per
administration or cumulatively, which is above the maximum recommended dose
according to the authorized product information. Clinical judgement should always be
applied.

- Antimicrobial resistance is the ability of microorganisms to survive in the presence of

antimicrobials. New resistance mechanisms are emerging and spreading, threatening
the ability to treat common infectious diseases. This is a major threat to global health
that requires global collaboration and action. Without effective antimicrobials, medical
procedures such as organ transplantation, cancer chemotherapy and major surgery
become very risky.

- Occupational exposure this refers to adverse outcome occur due to the exposure to a
medicinal product, as a result of one’s professional or non-professional occupation.

• Quality of Medicines scope of pharmacovigilance includes the monitoring of safety

problems related to the quality of medicines which includes poor manufacturing practice,
substandard and falsified medical products and lack of efficacy.

9
 - Poor manufacturing, storage or distribution practice is when the quality standards
specified are not met. In addition to Good Manufacturing Practice, there are also
guidelines on best practices for storage, transportation and distribution of
pharmaceuticals to ensure that medicines remain of high quality all the way to the
patient. If these quality standards are not met, it may lead to product contamination,
wrong amount of active ingredient or incorrect labels, resulting in ineffective treatment,
adverse effects or even death.
- Falsified medicinal products deliberately misrepresent their identity, composition or
source, for example by containing the wrong amount of the active ingredient, no active
ingredient at all or other ingredients.
- Lack of efficacy is defined as unexpected failure of a medicine to produce the intended
effect as determined by previous scientific investigation. Since lack of efficacy may be a
consequence of poor manufacturing practice or substandard and falsified medicines, it
could indicate a quality problem. Lack of efficacy may have serious implications for the
patient.

• The Broader Scope of Products

Another aspect to consider is the broad scope of products that fall under the
pharmacovigilance umbrella including:
- Medicinal products
- Biotherapeutics and vaccines
- Medical devices
- Dietary supplements
- Traditional medicines
- Cosmetics
- Veterinary medicines

Classification of adverse drug reactions

Type A (augmented) reactions: result from an exaggeration of a medicinal product’s normal
pharmacological actions and are normally dose-dependent. Examples include respiratory
depression with opioids or bleeding with warfarin. Type A reactions also include those that are
not directly related to the desired pharmacological action of the medicinal product, for example
dry mouth that is associated with tricyclic antidepressants.

10
Type B (bizarre) reactions are novel responses that are not expected from the known
pharmacological actions of the medicinal product. These are less common, and so may only be
discovered for the first time after a medicinal product has already been made available for
general use. Examples include anaphylaxis with penicillin or skin rashes with antibiotics.

Type C, or ‘continuing’ reactions, persist for a relatively long time. An example is osteonecrosis
of the jaw with bisphosphonates.

Type D, or ‘delayed’ reactions, become apparent sometime after the use of a medicinal
product. The timing of these may make them more difficult to detect. An example is
leucopoenia, which can occur up to six weeks after a dose of lomustine.

Type E, or ‘end-of-use’ reactions, are associated with the withdrawal of a medicinal product. An
example is insomnia, anxiety and perceptual disturbances following the withdrawal of
benzodiazepines.

Type F ‘Failure of therapy’ reaction

11
 The National Pharmacovigilance system in Sri Lanka

The National Pharmacovigilance Center in Sri Lanka is based in the National Medicines
Regulatory Authority. It is responsible for the safety monitoring of medicines in Sri Lanka and is
taking all the appropriate measures to:
• Maintaining the national reporting system as well as the relevant regulatory framework;
• Raise awareness about pharmacovigilance and encourage healthcare professionals and
patients to report the suspected adverse reactions and other medicines related
problems;
• Collect, manage & analyze national ICSRs to identify new medicines risks, furthermore,
report these ICSRs to the global database as appropriate;
• Ensure introduction of risk minimization measures and providing effective
communication on aspects related to medicines safety;
• Apply resulting information from pharmacovigilance and take the appropriate
regulatory actions for the benefit of public health programs, individual patients and
national policies related to medicine and treatment guidelines;
• Monitor compliance of the pharmaceutical companies to ensure the fulfillments of their
pharmacovigilance obligations of their medicines for the sake of patient safety.

Approaches for medicines safety surveillance

Passive surveillance (of spontaneous reports)
A surveillance method that relies on healthcare providers and consumers to take the initiative
in communicating suspicions of adverse drug reactions that may have occurred in individual
patients to a spontaneous reporting system.
Active surveillance
A system for the collection of case safety information as a continuous pre-organized process.
Active surveillance can be:
1. Drug based: identifying adverse events in patients taking certain products;
2. identifying adverse events in certain healthcare settings where they are likely to present for
Treatment
3. Event based: identifying adverse events that are likely to be associated with medicinal
products, e.g., liver failure.

12
National reporting system
Spontaneous reports are the most common source of information in the pharmacovigilance
system of Sri Lanka. In line with this general scope of pharmacovigilance the reporting system
in Sri Lanka is not limited to the adverse drug reactions. It also includes lack of efficacy,
medication errors, quality defects, counterfeit medicines, abuse or misuse interactions of
medicines, off-label use and occupational exposure. On some occasions there may be an inter
relation among these elements. For example, complaint received as an incident of lack of
efficacy may be due to a counterfeit product. Cluster of adverse reactions may reveal a serious
quality defect of a particular product. Irrespective of the type of the problem it affects the
safety of medicinal products.

Information needed for adverse reaction reporting

Reporting forms have been designed to collect the essential information required for proper
assessment of the ADR case report. Information to be filled in the ICSR forms can be
categorized under the following headings.

1. Patient 2. Suspected 3. Adverse reactions 4. Reporter

information medicine(s) Description Information
Information
- patient identifier - name (INN and brand - description of event or - name, address
- age at time of event name) problem and telephone
or date of birth - dose, frequency & route - date of event number
- gender used - date of this report - specialty and
- weight - therapy date - relevant tests/laboratory occupation
- diagnosis for use data, clinical measurements
- batch number (if available)
- expiration date - other relevant patient
information/history
- concomitant medical
- event abated after use
products and therapy
dates stopped or dose reduced
- event reappeared after
reintroduction of the
treatment
- Information on
management of the adverse
reactions and final outcome.

13
In order to overcome high level of missing data in the ADR reports on suspected anaphylactic
reactions PV division has introduced a separate form for reporting of anaphylaxis which would
capture all the important data.

Seriousness of Adverse drug reactions

A serious adverse reaction is any untoward medical occurrence associated with the use of a medicinal
product in a patient that at any dose, the patient outcome is one of the following:

1. Death
Report if the patient's death is suspected as being a direct outcome of the adverse reaction.

2. Life-Threatening
Report if the patient was at substantial risk of dying at the time of the adverse reaction or it is
suspected that the use or continued use of the product would result in the patient's death.

Examples: Pacemaker failure; gastrointestinal hemorrhage; bone marrow suppression; infusion

pump failure which permits uncontrolled free flow resulting in excessive medicine dosing.

3. Hospitalization (initial or prolonged)

Report if admission to the hospital or prolongation of a hospital stay results because of the
suspected adverse reaction.

Examples: Anaphylaxis; pseudomembranous colitis; or bleeding causing/ prolonging the existing

hospitalization.

4. Disability
Report if the adverse reaction resulted in a significant, persistent, or permanent disability/
incapacity; (change, impairment, damage, or disruption in the patient's body function/structure,
physical activities, or quality of life).
Examples: Cerebrovascular accident due to medicine-induced hypercoagulability; toxicity;
peripheral neuropathy.

5. Congenital Anomaly
Report if there are suspicions that exposure to a medical product prior to conception or during
pregnancy resulted in an adverse outcome in the child (birth defect).

Examples: Vaginal cancer in female offspring from diethylstilbestrol during pregnancy;

malformation in the offspring caused by thalidomide.

6. Medically important event or reaction

14
 Medical and scientific judgment should be exercised in deciding whether other situations
should be considered serious such as important medical events that might NOT be
immediately life-threatening or result in death or hospitalization but might cause danger to
the patient or might require intervention to prevent one of the other outcomes listed in the
definition above.
Examples:
§ Acetaminophen overdose-induced hepatotoxicity requiring treatment with
acetylcysteine to prevent permanent damage;
§ Burns from radiation equipment requiring medicine therapy;
§ Breakage of a screw requiring replacement of hardware to prevent in appropriate
healing of a fractured long bone.
§ Any suspected transmission via a medicinal product of an infectious agent is also
considered a serious adverse reaction.
§ Intensive treatment in an emergency room or at home for allergic bronchospasm,
§ Convulsions that do not result in hospitalization,
§ Development of medicine dependency or medicine abuse

Unexpected Adverse Reaction

An adverse reaction, the nature or severity of which is not consistent with the applicable
product information (e.g., Investigator’s Brochure for an unapproved investigational product or
package insert/summary of product characteristics for an approved product). i.e. expected and
unexpected ADR can refer to labeled vs unlabeled (for official data sheets/package inserts for
marketed products)

The concept of “expectedness” refers to events which may or may not have been previously
observed and documented. It does not refer to what might have been anticipated (expected in
a different sense) from the known pharmacological properties of the medicine.

Priorities for reporting

Pharmacovigilance Division encourage to report even seemingly insignificant or common
adverse drug events as it is required to establish a reporting culture in Sri Lanka. However,
more emphasis should be made on the following categories.

• All suspected reactions for new medicines

• All serious or unexpected suspected reactions for established or well-known medicines
• Increased frequency of a given reaction

15
 • All suspected ADRs associated with medicine– medicine, medicine – food or medicine –
food supplements
• ADR on special field of interests such as medicine abuse, misuse
• Medicines used during pregnancy and during lactation resulting in harmful effect to the
fetus or infant
• Teratogenicity due to medicinal product
• Suspected ADRs associated with medicine withdrawals
• ADRs due to overdose or medication error
• Lack of efficacy or pharmaceutical defects
• ADRs due to use of medicinal products in children under the age of 18
• Any ADR for medicinal products under the Black triangle scheme ▼

Black triangle scheme (intensified spontaneous reporting)

New medicines and vaccines that are under additional monitoring have an inverted black
triangle symbol (▼) displayed in their package leaflet and summary of product characteristic,
together with a short sentence explaining what the triangle means – it does not mean the
medicine is unsafe. All suspected ADRs for these products should be reported.

How to recognize ADRs in patients

ADRs are difficult and sometimes impossible to distinguish from the disease being treated since
they may act through the same physiological and pathological pathways. However, the
following approach is helpful in assessing possible drug-related ADRs:
1. Ensure that the medicine ordered is the medicine received and actually taken by the patient
at the dose advised.
2. Take a proper history of patient
§ A full medicine and medical history should be taken
§ An ADR should be the first differential diagnosis at all times
3. Establish time relationships by answering the following question: Did the ADR occur
immediately following the medicine administration?
Some reactions occur immediately after the medicine has been given while others take time
to develop. The time from start of therapy to the time of onset of the suspected reaction
must be logical.
4. Carry out a thorough physical examination with appropriate laboratory investigations if
necessary:
16
 § Remember: only a few medicines produce distinctive physical signs
§ Exceptions include fixed medicine eruptions, steroid-induced dermal atrophy, acute
extra-pyramidal reactions
§ Laboratory tests are important if the medicine is considered essential in improving
patient care or if the laboratory tests results will improve management of the patient.
§ Try to describe the reaction as clearly as possible- Where possible, provide an accurate
diagnosis
5. Analyze the alternative causes (other than the drug) that could on their own have caused
the reaction;
6. Effect of Dechallenge and Rechallenge should be determined
§ Dechallenge (withdrawal of the suspected medicine):
Positive dechallenge is the improvement / resolution of ADR when the suspected
medicine is withdrawn in a strong, though not conclusive indication of medicine-induced
reaction.
§ Rechallenge (re-introducing the suspected medicine after a dechallenge)
Rechallenge is only justifiable when the benefit of reintroducing the suspected medicine
to the patient overweighs the risk of recurrence of the reaction, which is rare. In some
cases, the reaction may be more severe on repeated exposure. Rechallenge requires
serious ethical considerations.
7. Report any suspected ADR or safety incident to the Pharmacovigilance Division or the
pharmaceutical company relevant to the suspected medicinal product.

Who can report?

All Medical Professionals Preferably Doctors, Dentists, Pharmacists, Nurses and Family
practitioners, Traditional medicine practitioners can submit ADR reports to the PV division. Also
patients & their relatives are encouraged to report.

How to report
• Online:
An online ICSR reporting portal has been enabled to facilitate the reporting of adverse
reaction and collecting all relevant information in a structured way. Upon submitting the
report, a confirmation message with Report ID will appear. This report ID should be saved
by the reporter and used when case follow up information is to be reported later.

17
 This online reporting can be accessed through the National Medicines Regulatory Authority
(NMRA) website on the following link
(https://nmra.gov.lk/index.php?option=com_contact&view=reporting&Itemid=191&lang=e
n)

QR Code

• Reporting form:

ICSR forms for reporting ADRs is available on the web site of the NMRA
(https://nmra.gov.lk/images/PDF/suspected_adverse_reaction_to_medicinesborderline_pr
oducts.pdf) for download. In addition, printed copies of the forms have been distributed
among the pharmacy departments/sections of the government health care institutes.
Requests from the health care professionals or institutes for reporting forms should be
made to the Pharmacovigilance Division of the NMRA. Fill in this form & send it back to the
NMRA on contact details included in the reporting form.

Timelines for reporting

Any suspected ADR should be reported as soon as possible. In case of serious adverse events
reporting should be done within 24 hours. Delay in reporting will make reporting inaccurate
and unreliable. If possible, report while the patient is still in the health facility this gives a
chance to reporter to clear any ambiguity by re-questioning or examining the patient.

Q&A
Must I be sure that a reaction was caused by the medicine
before reporting it?
No, it can be hard to tell whether a medicine caused a possible
adverse effect.
To report, you only need to suspect that the reaction was related
to the medicine.

18
Reporting Follow up information
Information may become available to the reporter after sending the initial report upon follow
up of the case e.g. clinical management of the adverse event or patient final outcome regarding
whether the event resolved or not, in this case the reporter should report this follow-up
information as “follow up report” and quote the unique reference number from the previous
report generated by the online reporting portal.

Will reporting have any negative consequences on the reporter?

• The adverse drug reaction report does not constitute an admission that the reporter or any
other health professional or the medicine contributed to or caused the reaction in any way.

• The outcome of the report, together with any important or relevant information relating to
the reported reaction, will be communicated to the reporter as appropriate.

• The details of the report are stored in a confidential database at the PV division and the
analyzed report will be sent to the Uppsala Monitoring Center (UMC).

• The names of the reporters or any other health professionals named on the report and the
patient will be removed before any details about a specific adverse drug reaction is used or
communicated to others.

• The information obtained from the report will not be used for commercial purposes. It is
only meant to improve our understanding and use of medicines.

What are the benefits of reporting on Healthcare professionals and patients?

The health care professional and patient stand to benefit as follows:
• Improvement on the quality of care offered to patients

• Reduction of medicines-related problems leading to better treatment outcome

• Improved patient confidence in the professional’s practice and consequently professional

growth

• Improved knowledge, access to feedback information on drug related problems reported

within the country and internationally

• Satisfaction for the fulfillment of moral and professional obligation

19
What Happens after reporting ADRs
Upon reporting, it is crucial that reporters fill in all the fields on the reporting form and
provide full description of the adverse reaction(s) as well as the circumstances that led to
them- all the information is important.
All reports sent by healthcare professionals or patients are collected by the pharmacovigilance
division, where the responsible pharmacovigilance specialist would ensure that the form has
all the essential information before proceeding to perform case assessment. All received
reports are entered in the national database (Vigiflow)
In some cases, the pharmacovigilance division will need to learn more about what happened
or to collect missing information, so they contact back the reporter for follow up. This follow-
up information can be obtained, via one or more of the following email, telephone call,
message on WhatsApp or similar application, and/or site visit and/or a written request. It is
important to continue follow-up and report new information until the outcome has been
established or the condition is stabilized.
In specific situations where the product quality is suspected, the reporter/reporting institute
may be asked by the pharmacovigilance specialist to submit the samples of the suspected
medicinal product for laboratory testing directly to the National Medicines Quality Assurance
Laboratory (NMQAL). If it is required to do so, samples should always be submitted with the
required information.

Complaints received from medical professionals, patients, mass media and the data base of the
Medical Supplies Division (MSD) may also trigger collection of further details.

All the collected reports will be analyzed at the national level, serious adverse effects will be
processed and analyzed in priority. Furthermore, all national report will also be sent to the
global database (Vigibase) where reports from all over the world are stored and analyzed.
Upon data analysis experts will discuss the following points:
• Is the report about something which is already known about the medicinal product? Or is
it new?
• Is the report isolated? Or have other patients/healthcare professionals reported similar
events?
• How frequent is this? How many patients are concerned, out of the total number of
patients treated?
• Is the adverse event likely to be caused by the medicinal product, or not?
• If it is confirmed that this is a new effect caused by the medicinal product, which measures
should be taken?
One or more regulatory action may be taken as detailed below

20
 Every report counts
A single case report should be seen as a piece of a jigsaw puzzle,
where further data and more reports are usually needed to
complete the picture.

Taking regulatory action to minimize risk

Upon analyzing the reported adverse reaction reports, once it has become clear that an adverse
effect results from the use of medicinal product, steps are taken to publicize the new
information and to minimize the risk of the adverse effect.

Actions might include:

• adding the new adverse effect to the existing list of adverse effect in the package insert of
the medicinal product

• restricting the uses of the medicinal product, revising the dosage recommendations, issuing
advice on precautions (e.g. by introducing special monitoring), or contraindicating the
medicinal product in some circumstances

• changing the arrangements for supplying the medicinal product (e.g. making a previously
over the-counter medicinal product to one that can be supplied only on a prescription)

• encouraging the reporting of all suspected adverse effects by placing the medicinal product
on a list of more intensively monitored medicines or black triangle scheme

• rarely, removal of the medicinal product from the market if the risks outweigh the its
benefits

• for important medicinal products found to have serious adverse effects, introducing special
measures such as registering all patients taking the medicinal product and supplying the
medicinal product only on the condition that the patient undergoes specific screening

Patients and health professionals reporting suspected adverse drug reactions help contribute to
these important processes.

21
Safety and Risk Evaluation Sub Committee (SAFRESC)
There would be an expert committee appointed by the NMRA which shall be named as Safety
and Risk Evaluation Sub Committee (SAFRESC). The Committee provides advices and technical
assistance to the division pertaining to the subject.

Members of the SAFRESC

1. Head of the PV Division

2. Two Pharmacologists from two different recognized universities in Sri Lanka
3. Two pharmacists attached to the PV unit
4. Immunologist, Medical Research Institute
5. Consultant Physician, NHSL
6. Director, NMQAL
7. Chief Pharmacist Technical Unit of NMQAL
8. Representative from the FHB
9. Representative from the Epidemiology Unit
10. A pharmacist representing MSD

Members of the SAFRESC would be appointed according to an approved procedure. Each

appointment would be valid for a period of 3 years.

Pharmacovigilance and the role of pharmaceutical companies

It is mandatory for pharmaceutical companies (including manufacturers and importers) in order
to register products for use in Sri Lanka to have a pharmacovigilance system capable of
monitoring the safety of their medicinal products. This include collection, management and
submission of ADRs & other safety incidents to the Pharmacovigilance Division at the NMRA,
analyze the collected safety data to identify new risks, and bring to the attention of the NMRA
to any foreign regulatory decisions taken in relation to the safety of their medicinal products.
Furthermore, as a part of their pharmacovigilance practice, pharmaceutical companies shall
adopt the appropriate risk management measures to ensure the safe & effective use of their
medicinal products. In specific circumstances they may be requested by the NMRA to conduct
post-authorization safety/ efficacy studies when needed.

Pharmacovigilance in Public Health Programmes

The objective of the Public Health Programmes is to promote health and reduce morbidity and
mortality due to major common diseases e.g immunization programmes, Anti- HIV, Anti-
tuberculosis, Anti- malaria, Anti- filariasis and Anti- Leprosy programs. It is common to expose
22
large populations to medicines to prevent a disease, although only a small proportion of the
population is affected. The goal is to eliminate the disease as a public health problem.
Since the medicinal products used in Public Health Programmes may be new and have limited
safety information for the specific target population, it is important to have a system in place to
monitor safety.
Accordingly, it is very important to integrate Pharmacovigilance in Public Health Programmes
for better capturing, recording and reporting of adverse drug reactions and other safety
incidents.

23
APPENDIX: (01) ADR REPORTING FORMS

24
APPENDIX: ANAPHYLAXIS REPORTING FORMS

25
Page 2

26
APPENDIX: ADR Electronic Reporting
0
Select patient or
Healthcare professional
reporting

1
Enter Patient
information

Enter in details the

adverse reaction(s)
and the circumstances
leading to this
harmful effect

Press here if there

are other adverse
reactions for the
same case

27
 3
Enter details of
Suspected medicine

Press here if there

are other suspected
medicines for the
same case

28
 4
Enter description of
medical history,
special diets,
recreational drugs,
smoking habits,
alcohol intake or
allergies

Pregnancy status
for women

Enter the reporter

details

6
Save your report ID
& use it when
reporting follow-
up information for
the same report

29
References
• CIOMS Cumulative Pharmacovigilance Glossary: Version 1.0, Council for International
Organizations of Medical Sciences, 2021

• Safety of Medicines, A guide to detecting and reporting adverse drug reactions. World
Health Organization (WHO) Geneva 2002

• Safety monitoring of medical products: reporting system for the general public. World
Health Organization (WHO), 2012

• Safety Monitoring of Medicinal Products, Guidelines for setting up and running a

Pharmacovigilance Centre. the Uppsala Monitoring Centre (the UMC), WHO Collaborating
Centre for International Drug Monitoring, 2000

• Guidance on adverse drug reactions, YellowCard, Medicines and Healthcare Products

Regulatory Agency, UK

30