STANDARD Written By: COPY TO ****************

OPERATING Dr. E. Muigai

PROCEDURE NO: QA/RA Pharmacist
QA/***/X ____________________
Edition No.: X
Approved By:
PROCEDURE FOR Mr. ___________
Supersedes Edition: IX
SIGNAL Dr. _______
DETECTION AND Effective Date:
RISK Dr. _________
MANAGEMENT Authorised By: Review Date:
Mr. N. Shrivastava
Q.A. Manager __________________

1.0 PURPOSE:
The purpose of this SOP is to identify and analyse new signal from reported cases whilst
developing a robust risk management ratio of the marketed product. Further to that, Ely
chemical industries shall communicate the safety information on use of medicines
manufactured to the relevant Health Authorities, Health Care Practioners and the general
public.
RESPONSIBILITY:
The Qualified Person for Pharmacovigilance/Deputy QPPV shall be responsible for the
identification of suspected and or detected safety signals and the update to the risk-benefit
profile for Elys Chemical Industries products. Management team shall be responsible for the
review and approval of recommendation for action in all safety signals.

No change in this SOP may be made without authority.

Introduction:
What Is A Safety Signal?
The definition of a signal as provided by the council for international organizations of
medical sciences (CIOMS) Working Group 8is: “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 an intervention and an event or
set of related events, either adverse or beneficial, that is judged to be of sufficient likelihood
to justify verificatory action”.
In essence, a signal is a hypothesis of a risk associated with medicine along with supporting
data. The evidence in a signal is an early indication and not definitive as it substantially
changes as the data accumulates over time. The evaluation of safety signals should be a

Page 1 of 9
STANDARD Written By: COPY TO ****************
OPERATING Dr. E. Muigai
PROCEDURE NO: QA/RA Pharmacist
QA/***/X ____________________
Edition No.: X
Approved By:
PROCEDURE FOR Mr. ___________
Supersedes Edition: IX
SIGNAL Dr. _______
DETECTION AND Effective Date:
RISK Dr. _________
MANAGEMENT Authorised By: Review Date:
Mr. N. Shrivastava
Q.A. Manager __________________

continuous process in pharmacovigilance as it is imperative for Elys Chemical Industries to

have a well-defined process to capture, evaluate and take immediate action on potential PV
risks as needed. A signal may be generated either by statistical analysis or by qualitative
analysis of spontaneous reports.
Signal Management
The process of signal management in pharmacovigilance consists of a set of activities that
aim to determine if there are new risks associated with an active substance or a medicinal
product or whether known risks have changed based on a thorough analysis of individual
case safety reports (ICSRs), aggregate data from active surveillance systems or scientific
literature. The set of activities includes the following steps:
i. Signal Detection.
ii. Signal Validation.
iii. Signal Prioritisation.
iv. Signal Assessment.
v. Recommendation for action.
vi. Exchange of information.

2.0 PROCEDURE:
2.1.1 Monthly Operation: On 15th and the preceding five days of every month the
QPPV/Deputy QPPV shall conduct all the signal management activities. These shall
include-;
2.1.2 Signal Detection.
2.1.2.1 The QPPV/Deputy QPPV shall review form ***under review******
that shows monthly product adverse event (ADR)/product quality
complaint reconciliation, form ******under review***** that shows

Page 2 of 9
STANDARD Written By: COPY TO ****************
OPERATING Dr. E. Muigai
PROCEDURE NO: QA/RA Pharmacist
QA/***/X ____________________
Edition No.: X
Approved By:
PROCEDURE FOR Mr. ___________
Supersedes Edition: IX
SIGNAL Dr. _______
DETECTION AND Effective Date:
RISK Dr. _________
MANAGEMENT Authorised By: Review Date:
Mr. N. Shrivastava
Q.A. Manager __________________

Monthly literature review reconciliation ********under

review********** ,available aggregate reports and data collected as
per the regulatory intelligence SOP .The result identified sources of PV
data in the aforementioned period for any potential signal shall be
logged in the safety signal investigation report on annexure 1.
2.1.3 The QPPV/Deputy QPPV shall determine if a new or potential safety signal that exist
warrants further investigation including-;
2.1.3.1 New AEs, that has not been recorded especially if they are serious and
have occurred in rare sub-population.
2.1.3.2 Apparent increase in the severity of an AE.
2.1.3.3 Occurrence of a Serious Adverse Event known to be extremely rare in
the general population.
2.1.3.4 Previously unrecognised interactions with other products, supplements
or foods.
2.1.3.5 Identification of a previously unrecognised at risk-patient population or
sub group of patients, such as patients with specific medical condition,
comorbidities or with specific racial or genetic predisposition.
2.1.3.6 Adverse event arising from the way the product is being used either on
or off label (e.g. adverse event seen at doses higher than those normally
prescribed or in sub population not recommended in the label.
2.1.3.7 Adverse Event arising from user error, or from medication error.
2.1.3.8 Other concerns that may be identified by Elys Chemical Industries PV
department or the regulatory agencies.

Page 3 of 9
STANDARD Written By: COPY TO ****************
OPERATING Dr. E. Muigai
PROCEDURE NO: QA/RA Pharmacist
QA/***/X ____________________
Edition No.: X
Approved By:
PROCEDURE FOR Mr. ___________
Supersedes Edition: IX
SIGNAL Dr. _______
DETECTION AND Effective Date:
RISK Dr. _________
MANAGEMENT Authorised By: Review Date:
Mr. N. Shrivastava
Q.A. Manager __________________

2.1.4 Signal Validation

2.1.4.1 Strength of the association with the product
2.1.4.2 Evidence of dose response Effect
2.1.4.3 Frequency; that is, for example the number of spontaneous reports in
comparison to earlier periods and/or in relation to estimated patient
exposure; same type of information in context of clinical trial data.
2.1.4.4 Quality of the reports. Completeness of data, plausibility of the
information, availability of data to substantiate reported diagnosis.
2.1.4.5 Reporter and company causality assessment of individual cases.
2.1.4.6 Temporal relationship of product use and event including information
on de-challenge and re-challenge.
2.1.4.7 Consistency of data patterns indicating potential risk groups
2.1.4.8 Consistency of findings across available data sources.
2.1.4.9 Specificity of case series (for example histopathology or subtype of a
disorder is reported in all cases of a series of events)
2.1.4.10 Alternative medical or technical explanations.
2.1.4.11 Seriousness and severity of the reaction and its outcomes, relative to
disease being treated.
2.1.4.12 Drug-drug interaction
2.1.4.13 Potential to mitigate the risk in the population.
2.1.4.14 Degree the benefit the product provides, including the availability of
other therapies
2.1.4.15 Extent to which information is included.
2.1.4.16 After investigation of the safety signal, the conclusion can be-;

Page 4 of 9
STANDARD Written By: COPY TO ****************
OPERATING Dr. E. Muigai
PROCEDURE NO: QA/RA Pharmacist
QA/***/X ____________________
Edition No.: X
Approved By:
PROCEDURE FOR Mr. ___________
Supersedes Edition: IX
SIGNAL Dr. _______
DETECTION AND Effective Date:
RISK Dr. _________
MANAGEMENT Authorised By: Review Date:
Mr. N. Shrivastava
Q.A. Manager __________________

2.1.4.16.1 Validated and accepted: A causal relationship between the

product and the event is assumed.
2.1.4.16.2 Not validated and rejected: no causal association between
the product and the event is assumed or
2.1.4.16.3 Pending, not confirmed signal: No clear conclusion
regarding causality can be drawn. The signal is further
monitored and re-evaluated at a defined point.
2.1.5 Signal Prioritization
2.1.5.1 The QPPV/Deputy QPPV shall assess-;
2.1.5.2 Impact on the patient depending on severity and reversibility, and
potential for prevention and clinical outcome.
2.1.5.3 Consequences on treatment discontinuation and on the disease and the
availability of other therapeutic options.
2.1.5.4 Strength and consistency of the evidence supporting the association.
2.1.5.5 Clinical context
2.1.5.6 Public health impact.
2.1.5.7 The QPPV/Deputy QPPV shall enter the outcome of signal
prioritization on the remarks section of the safety signal invrstigation
report.
2.1.6 Signal Assessment
2.1.6.1 The QPPV/Deputy QPPV shall-;
2.1.6.2 Review internal and external sources to obtain further information.
2.1.6.3 Document the risk assessment of the signal per product safety signal
investigation report, and recommend no further action, or further action

Page 5 of 9
STANDARD Written By: COPY TO ****************
OPERATING Dr. E. Muigai
PROCEDURE NO: QA/RA Pharmacist
QA/***/X ____________________
Edition No.: X
Approved By:
PROCEDURE FOR Mr. ___________
Supersedes Edition: IX
SIGNAL Dr. _______
DETECTION AND Effective Date:
RISK Dr. _________
MANAGEMENT Authorised By: Review Date:
Mr. N. Shrivastava
Q.A. Manager __________________

to prevent or minimise patient risk as described in the recommendation

for action.

2.1.7 Recommendation for Action

2.1.7.1 The QPPV/Deputy QPPV shall submit to the management team to
make a decision that shall authorise-;
2.1.7.2 Initiation of Health Hazard Assessment for potential field action.
2.1.7.3 Request of quality complaint for further product evaluation.
2.1.7.4 Expedited reporting to regulatory authorities
2.1.7.5 Direct healthcare professional communication (DHCP
communication)/Dear Doctor letters.
2.1.7.6 Continued assessment of the product benefit-risk balance.
2.1.7.7 Further investigation of the safety risk through additional studies.
2.1.7.8 Development of a pharmacovigilance plan focused on identifying the
available risks.
2.1.7.9 Reporting via periodic report submission.
2.1.7.10 Risk management document updates.
2.1.7.11 Additional educational material or training.
2.1.7.12 Modification of the ongoing monitoring strategy of the product
2.1.7.13 Initiation of the label change and or other external communication
activities.
2.1.7.14 Initiation of recall/correction procedure
2.1.7.15 Information to concerned health authorities.
2.1.7.16 Issuing or updating a Risk Management Plan
2.1.7.17 Introduction of enhanced pharmacovigilance activities

Page 6 of 9
STANDARD Written By: COPY TO ****************
OPERATING Dr. E. Muigai
PROCEDURE NO: QA/RA Pharmacist
QA/***/X ____________________
Edition No.: X
Approved By:
PROCEDURE FOR Mr. ___________
Supersedes Edition: IX
SIGNAL Dr. _______
DETECTION AND Effective Date:
RISK Dr. _________
MANAGEMENT Authorised By: Review Date:
Mr. N. Shrivastava
Q.A. Manager __________________

2.1.7.18 Introduction of additional Risk Minimisation Activities

2.1.7.19 Conducting a post authorisation safety studies.
2.1.7.20 Periodic review of a signal.
2.1.8 Exchange of information
2.1.8.1 The QPPV/Deputy QPPV shall-;
2.1.8.2 Communicate immediately to the management team an Emerging
Safety Signal with all validated signal pointing towards an implication
for public health or the benefit risk profile of a specific product.
2.1.8.3 Depending on the severity of the signal, communicate validated signals
representing a new potential signal or a new aspect of a known risk and
not having implication for the benefit risk profile to applicable
regulatory authority.
2.1.8.4 Communicate the outcome of signal assessment involving new or
changed risk to the public including the healthcare professionals and
patients as well as Local Technical Representatives in the respective
countries.

Page 7 of 9
STANDARD Written By: COPY TO ****************
OPERATING Dr. E. Muigai
PROCEDURE NO: QA/RA Pharmacist
QA/***/X ____________________
Edition No.: X
Approved By:
PROCEDURE FOR Mr. ___________
Supersedes Edition: IX
SIGNAL Dr. _______
DETECTION AND Effective Date:
RISK Dr. _________
MANAGEMENT Authorised By: Review Date:
Mr. N. Shrivastava
Q.A. Manager __________________

3.0 ANNEXURE:

ANNEXURE
TITLE OF THE ANNEXURES FORM NO.
NO.
Annexure I Safety Signal Investigation Report

4.0 ABBREVIATIONS:

Page 8 of 9
STANDARD Written By: COPY TO ****************
OPERATING Dr. E. Muigai
PROCEDURE NO: QA/RA Pharmacist
QA/***/X ____________________
Edition No.: X
Approved By:
PROCEDURE FOR Mr. ___________
Supersedes Edition: IX
SIGNAL Dr. _______
DETECTION AND Effective Date:
RISK Dr. _________
MANAGEMENT Authorised By: Review Date:
Mr. N. Shrivastava
Q.A. Manager __________________

SR.NO. ABBREVIATIONS FULL FORM

01 QPPV Qualified Person for Pharmacovigilance

02 PV Pharmacovigilance
03 ICSR Individual Case Safety Report
04 AEPQC Adverse Events Product Quality Complaints
05 DHCP Dear Healthcare Practioners

5.0 REVISION HISTORY:

EDITION EFFECTIVE
REVISION SUMMARY
NO. DATES

I Need for an SOP was realised.

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