Product Quality Complaints

PRODUCT QUALITY COMPLAINTS
(PQCs)
(QS000049)
GQS Version: 1.0
Training PPT Version: 1.0
For Your Kind Attention Please……
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listening the session.
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© Sun Pharmaceutical Industries Limited. All Rights Reserved. 2

OBJECTIVE
This Global Quality Standard

(GQS) defines the
requirements for receiving,
tracking, investigating,
responding to, reporting and
resolving PQCs.

Sun Pharma Manufacturing Sites
Market Companies
Licensees
Contract Manufacturing Organizations (CMOs)
Contract Laboratories.

• In case of CMOs wherein Sun Pharma is the
marketer of the product and not the MAH,
whenever Sun Pharma receives a PQC, it shall
send the information regarding the PQC to
the CMO.
• Processing of PQC shall be CMOs

responsibility and applicability of this GQS in
such a case is limited to only Sun Pharma’s
Accountabilities.
• Accountabilities of Sun Pharma and CMO in

PQC management shall be appropriately
captured in the Quality Agreements.
 Compliance with this GQS is mandatory and this GQS
is applicable globally to all Sun Pharma
manufacturing and testing locations/quality offices.
 Site Specific SOPs shall not ignore any point /

understanding given in this GQS.
 Sites shall prepare or revise their existing site specific

SOPs based on this GQS within a period of ninety (90)
days from its effective date.

EXCLUSIONS
Quality issues reported prior to distribution of the

product beyond the control area of Sun Pharma
quality systems (e.g. those reported from third
party testing laboratories / Batch Release Sites /
QPs, etc. prior to distribution of the product into the
market) are out of the scope of this GQS and shall
be processed through the “Deviations” or “Out-of-
Specifications” workflow, as applicable.
PQCs related to IMP / batches used for Clinical

Trials are also excluded from the scope of this
GQS.
RESPONSIBILITY
EACH MARKET COMPANY
Forwarding PQCs to Communicating

Corporate Quality adverse drug/device
Compliance Head events to the
and Site Quality Pharmacovigilance
Head / QP or (PVG) department.
designees, as
appropriate.
CORPORATE QUALITY COMPLIANCE HEAD / DESIGNEE
Assuring each Market Company is qualified to handle the

receipt, sorting and routing of PQCs and adverse
drug/device events.
Assuring there is a system for receiving and documenting PQCs,

adverse drug/device events, Medical Device Reportable Events
and that the information is available to both Quality Unit and
Pharmacovigilance (PVG).
Assuring the proper government health authorities are notified within the
required time period in the event of a reportable incident from PQC
information and investigations.

CORPORATE QUALITY COMPLIANCE HEAD / DESIGNEE
Evaluating on a routine and regular

basis, PQC summary reports from
the Sites to determine if trends
Maintaining exist and to take any necessary
all PQC corrective actions to resolve them.
records.
Performing Risk
Classification of the PQCs,
as applicable.

SITE QUALITY HEAD OR QUALIFIED PERSON (QP) / DESIGNEES
• Notifying Pharmacovigilance(PVG) when an adverse

drug/device event is reported to the site.
• Assessing whether an AE/LOE/Efficacy related PQC

requires quality investigation.
• Investigating, testing, resolving, documenting and closing

PQCs and for the evaluation and assessment of the impact
of the PQCs on other batches and/or products.
• Performing Risk Assessment and classification of PQCs.
• Defining and implementing corrective and preventive

actions.

HEAD PHARMACOVIGILANCE (PVG) / DESIGNEE
• Notify CQC of any adverse event on monthly basis through

email by providing a listing of AE reports received from
consumers or Health Care Professionals (HCPs) from the
market.
• Notifying the Site QA or designee of any adverse report that

may be related to drug/device quality.
• Assessing whether the PQC is associated with any AE, LOE

and/or Efficacy related issue.
• Performing Health Hazard Evaluations where applicable.

REGULATORY AFFAIRS (RA) HEAD / DESIGNEE
• Regulatory Agency notification of PQCs as required
Notes:
1. Additional responsibility detail is provided in the process

description and requirements sections of this GQS.
2. Responsibilities in this GQS are suggested based on

workflow. Individual sites may revise department names / roles
(but not the functionality) specific to region / site.

ABBREVIATIONS AND DEFINITIONS
TERM
Adverse Drug Experience Report
AE
CAPA
Contract Manufacturing Organization (CMO)/In License- Third Party
Manufacturing
Counterfeit Medicines
HHE (Health Hazard Evaluation)
IMP
Deviation
Product Quality Complaint Record
QP
LOE
Company Safety Database
Primary Source of the PQC

ABBREVIATIONS AND DEFINITIONS – CONTINUED
Term Definition
Market A wholly owned subsidiary of Sun Pharma organized to support
Company sales of country-specific products through distribution and
marketing.
PQC Product Quality Complaint: Any written, electronic or oral
communication reported by Customers, Physicians,Pharmacists,
Hospitals, Regulatory Agencies, Health Authorities, Government
Laboratories, MA Holders, Retailers, Distributors, etc., that alleges
deficiencies related to the safety, identity, strength, quality, purity
reliability and/or efficacy of a product after it is
distributed beyond the control area of Sun Pharma quality systems.
Complainant Any non-Sun pharma source from whom the PQC information is
received at Sun Pharma is called the Complainant. E.g. patients,
prescribers, pharmacists, nurses, hospitals, retailers, distributers, MA
holders.

ABBREVIATIONS AND DEFINITIONS – CONTINUED
Term Definition
Responsible Individual designated within a Country/Region/Site
Person for responsible for managing receipt of PQCs. The RP who
PQCs – also initiates the PQC Record is also referred to as the
called “Initiator.”
“Initiator”
Site Product Individual (preferably from QA) at the manufacturing site
Quality responsible for coordinating the Product Quality Complaint
Complaint investigation and communicating findings to the Responsible
(PQC)Coordina Person/Initiator and other persons as appropriate. The Site PQC
tor coordinator may also be the initiator of a PQC. The Site PQC
Coordinator is responsible for overall management of the PQC
processing in consultation with a Cross Functional Team (CFT)
assigned by Site Quality for support, as needed.
Company Any Electronic safety database used for capturing,
Safety processing, reporting and holding Adverse Event
Database information.

WORKFLOW : HANDLING OF PRODUCT QUALITY COMPLAINTS (PQC)
WORKFLOW Receipt & Logging of PQC by Responsible Person / Initiator *

Follow-up for Information, if needed
Sending of Acknowledgment Report to Complainant

If needed, alert RA Groups / QP
Follow either Step A 1 or Step A 2

A 1 A 2
Forwarding of PQC to Forwarding of PQC to Notification to RP, as needed

RP – RQ /QP / CMO- QA, as applicable Site PQC Coordinator (refer GQS)
Validity Assessment of PQC by PVG Validity Assessment: Yes

QA & PVG* in Parallel Is There any AE / LOE
Component
* - Not applicable for API Initiate Processing in
Site Safety System with copy / reference to
No PQC Record
PQC concluded as ‘Invalid’ by Site

QA & PVG Assessment: Complaint Coordinator with justification document Notification to RP, as needed
Is Quality Investigation Needed? No (refer GQS)
Notification to Regulatory
Yes (i.e., PQC concluded as ‘Valid’) Sending of Response Report
Authorities, as needed
to Complainant
(i.e., FAR)
Risk Assessment of PQC
(Critical / Major / Minor)
Product Recall Proposal, Closure of PQC as ‘Closed-Invalid‘

if needed
B
Blocking of Impacted
Batches in SAP/METIS, if needed Re-Activation to Re-Assess Validity
C
Quality Investigation of PQC PQC
HHE from PVG, if required
Root Cause Identification (In) QC Testing of Samples, if required

(ii) OOS Investigation, if required
Classification of PQC
(Critical / Major /Minor)
D
Summarization & Conclusion of PQC
Investigation Findings,
Preparation & Approval of Response Report CAPA Creation & Implementation
Un-Blocking of non-impacted batches in
SAP/METIS as Per Decision Taken
Product Recall Proposal,
if needed
Sending of Response Report to complainant totoCCCCComplainant
Note: Dotted Lines Indicate Optional activities
Closure of PQC PQC
Re-Activate to Re-Activate to Update Conclusion

C D
Re-Investigate

PROCESS DESCRIPTION
GENERAL INSTRUCTION
Management of PQCs shall be carried out

either through electronic systems, wherever
available or through manual documentation.
Wherever electronic system is being used, a
business continuity plan should be in place in
case of electronic system failure.

RECEIPT, LOGGING AND ACKNOWLEDGEMENT OF PQCs
PQC information received by written, electronic or oral

communication shall be accurately documented and sent to
the Responsible Person (RP) of the Country/Region/Site
identified for receipt of PQCs.
• Note: Each Market Company, Licensee, Contract

Manufacturer and Contract Laboratory shall be responsible
for forwarding: PQCs to Corporate Quality Compliance and
Site Quality Head or their respective designees, as
appropriate and Adverse Drug/device Events to the
Pharmacovigilance (PVG) department.

The recipient RP or designee shall initiate a PQC Record (i.e. log the
PQC) and accurately document the following information at a minimum:
• Each PQC Record shall be assigned a unique identifier for traceability.

• Name of RP or designee.
• Product details (Name, strength, dosage form of the product/device).
• Batch Number(s) as reported by Complainant (the RP or designee shall
indicate in the record cases where the PQC batch number is not
available at the time of logging in the PQC).
• Short description about the nature of the complaint and extent of the
alleged problem found.
• Any impact on health or safety reported by a reporter (consumer or

HCP).

• Contact information for Primary source of the PQC.

• Complainant name and contact information (if not available, this shall be
indicated in the record). Clearly state if Complainant and the Primary
Source are the same person.
• Channel for how PQC was received by Sun Pharma.
• Date of receipt of PQC at Sun Pharma.
• Date of receipt of PQC by Initiator or designee (The RP who initiates the
PQC Record will be henceforth referred to as “Initiator”).
• Market where PQC originated.
• Active Ingredient of the product (applicable only to Drug Product).
• Whether the PQC sample is available or has been received. If received,
scans/photos shall be attached to the PQC record.

• PQC records shall be created preferably on the day of receipt but

not later than end of next working day.
• All supporting, available documents as applicable shall be

attached to the PQC record.
Note: PQC details shall be logged in “English” language only.
• If information provided in the PQC record is insufficient to

definitively link the PQC directly to a Sun Pharma product (e.g.
information of batch/lot number or sample availability are
missing), then a minimum of five follow-up attempts shall be made
over a period of twenty (20) calendar days to contact the
Complainant by phone, e-mail, written communication, facsimile,
etc., by the Initiator or designee
• A report of each follow-up attempt shall be documented

and attached with the PQC record. If such follow-ups fail to
yield this information, non-availability of the information
shall be recorded in the PQC record.
Note: The number of follow-ups and the number of days as

specified above is to ensure that an adequate number of
follow-ups over an extended period of time are carried out.
• Separate PQC Records shall be generated for each

product when a single PQC involves more than one
product.

If a single PQC involves more than one batch of the same product,
then a single PQC Record may be generated if the following
parameters are the same for the implicated batches:
Primary Source of the PQC Nature of the PQC
The Initiator or designee, shall alert relevant Regulatory Affairs (RA)

groups/Qualified Person (QP) (only for EU products)/Site
Quality/Country Manager or other relevant individuals regarding the
PQC.

• The Initiator or designee shall send an Acknowledgment

Report/communication to the Complainant within five (5) working
days from the date of receipt of the PQC at Sun Pharma.
• An example template for a PQC Acknowledgement Report is

provided as Attachment I.
Note: Acknowledgement Report will not be sent in cases where the

complainant specifically states an Acknowledgement Report is not
desired, if the complainant details are not known or is deemed not
required by the Initiator or designee. Any situation in which the
decision is made to not send the Acknowledgement Report shall
require justification and will be recorded in the PQC Record.

ATTACHMENT I

After the Acknowledgement Report has been sent to the

Complainant,
• the Initiator or designee shall forward the PQC to the PQC
Coordinator at the manufacturing site of the product for
which PQC was received.
• The Site PQC Coordinator shall be responsible for overall

management of the PQC processing and investigation in
consultation with a Cross Functional Team (CFT) assigned
by Site Quality for support, as needed.

• If the manufacturing site is not known, the Initiator shall

forward the PQC to the relevant RP – Regional Quality (RQ)
/Qualified Person (QP)/Contract Manufacturing Organization
(CMO)/In License – Third Party Manufacturing -QA, as
applicable, who shall forward the PQC to the relevant
manufacturing site(s) for further processing.
• The PQC Initiator shall forward any PQC samples received

to the PQC coordinator of Site taking precautions to
maintain integrity of the samples. Availability/non-availability
of PQC samples, as well as photos or scans of these shall
be recorded in the PQC record.

PQC VALIDITY ASSESSMENTS (VALIDITY ASSESSMENTS SHALL BE CARRIED OUT
FOR EACH PQC IN PARALLEL BY THE SITE PQC COORDINATOR (QA), SITE
QUALITY HEAD /DESIGNEE AND PVG FOR ALL PQCs RELATED TO DRUG
PRODUCTS):
PQC Validity Assessment by Site PQC

Coordinator (QA) and Site Quality
If the Site PQC Coordinator

The Site PQC Coordinator shall observes that the PQC is for a
check validity of the PQC by Sun Pharma product, which is not
conducting a review of the manufactured at his/her site, the
authenticity of the PQC with PQC shall be forwarded to the
respect to the products Regional Quality/QP/
handled at the site by CMO-QA group (as applicable)
evaluation of the PQC sample, who shall then assign it to the
if available, authenticity of the appropriate Sun Pharma
lot/batch code, expiry dating or manufacturing site.
other evidence provided (e.g.
photos, scans, batch numbers)
and retain samples, as needed.

PRODUCTS):
• PQCs related to products not manufactured by or for Sun Pharma,

PQCs received where complete information (Product Name, Batch
No., etc.) cannot be obtained after five attempts and PQCs received
for products for which Sun Pharma is the marketer and another
manufacturer is the Market Authorization Holder (MAH) shall not
require implementation of a PQC Quality Investigation process and
the PQC shall be considered “Invalid”.
• Documented justification providing rationale to support this PQC

classification decision shall be approved by Site Quality Unit.

PRODUCTS):
• Incoming PQCs shall be evaluated on a case-by-case basis.
For Example:
Consider a PQC that has been received where the product name is available,
but batch number is not available.
Investigation of certain product quality defects can still be conducted based

on the history of the product and or the process, visual inspection and/or
testing of the PQC samples.
In such cases, the PQC should not be considered “Invalid” and the
investigation should be performed.

PRODUCTS):
For PQCs related to APIs and Intermediates, a PVG Assessment

is not required.
The PVG team shall evaluate the complaints, categorize

them as ADE + PQC or PQC and communicate to the Site
Quality team, Site PQC Coordinator or Corporate Quality
PQC Validity Compliance (CQC) as applicable to further classify the
Assessment complaints as critical, major or minor.
by PVG
Validity Assessment of a PQC by the PVG involves review
of each PQC to determine the following:
 Whether the PQC has any Adverse Event (AE) component.

 Whether the PQC has any Lack of Efficacy (LOE)/Efficacy
related component.

PRODUCTS):
All PQCs with valid AE/LOE/Efficacy issues shall require a mandatory

processing in the Company Safety Database if Sun Pharma or its affiliate is
the MAH for the product and case processing shall be carried out as per
current effective versions of applicable PVG SOPs. In such a case, the Case
ID shall be documented in the PQC Record log/document.
All PQCs related to LOE/Efficacy related issues shall also require a Quality
Investigation (those associated with off-label use, i.e., not an indication
approved by the product label or inappropriate product use may be exempted
with supporting rationale/justification documented in the PQC Record).

PRODUCTS):
A PQC Validity Logic Matrix is provided as Attachment II

providing rationale for supporting when a complaint is valid or
invalid for Quality Investigation based on:
 Whether a PQC has been filed by QA.

 Whether a valid Adverse Event has been filed by PVG.
 Whether a valid efficacy related issue has been confirmed by
PVG.
 Whether a Quality Investigation has been requested for AE
related complaints filed by PVG.

ATTACHMENT II Product Quality Complaint Validity Logic Matrix

ATTACHMENT II - CONTINUED

PRODUCTS):
PQCs for which complete Based on the PVG and Site

information was not Quality validity assessments of
received despite the the PQC, the Site PQC
specified number of Coordinator shall make a final
follow-ups shall also be decision about the PQC validity.
assessed for validity. This decision must be approved
by the Site Quality Unit.
• If the PQC is determined to be “Invalid”, the Site PQC Coordinator shall prepare
a Response Report for the PQC, detailing the validity assessment summary and
shall send it to the Initiator or designee, who shall forward it to the Complainant if
deemed necessary.
• Once the Initiator or designee confirms to the Site PQC Coordinator that the
Response Report has been sent to the Complainant, if applicable, the PQC
record may be closed as “Invalid”.
PRODUCTS):
Notification of the PQC as “Invalid” shall be sent to Initiator/ RP Regional

Quality/QP/Contract Manufacturing Organization-QA (as applicable), PVG, Site
Quality Head and other stakeholders.
• After a PQC has been closed and • If notification of the PQC to a

classified as “Invalid”, the Site Regulatory Agency is required it
Quality Head or designee, may, at a shall be handled by RA.
later date, allow its re-activation to
reassess its validity, if needed and • Responsibilities of personnel
process it further according to the involved in notification/coordination
PQC workflow. of PQCs related to information
• Re-activation of an “invalid” record required by Regulatory Agencies
shall be done only if deemed (e.g. QP-PV, QP-Batch Release,
necessary by Quality Head or etc.) shall be clearly specified in the
designee in concurrence with the site specific SOPs
CQC and shall be accompanied
with adequate justification and
rationale. .

RISK ASSESSMENT OF PQC
A Risk Assessment for all valid PQCs shall be conducted by the Site/ CMO PQC
Coordinator (QA) and Site Quality Head to assign the risk category of the PQC to
facilitate the following (but not limited to):
• Prioritization of investigations and thereby closure of PQC and Assessment for

the need for Product Recall.
A pre-investigation risk assessment shall be conducted preferably within one working

day, from date of receipt of PQC for prioritization of investigations, for assignment of
appropriate methods/tools for Root cause or cause(s) analysis and for determining
impact of the complaint on other products or batches available in market for human
consumption.

The following three factors shall be used to identify the level of risk
based on nature of the PQC:
Severity
Occurrence
Detection
A) Assessment of Severity/Impact of PQC on product quality and patient safety.

(What are the consequences?)
Note: The Site PQC Coordinator (QA) in conjunction with the Site Quality Head shall
assign a risk rating as per Table A below once a determination is made that the PQC
may represent a risk to the safety, identity, strength, purity and/or quality of the
product.

Risk Rating Criteria Table A: Severity of PQC – Rating and Criteria

Low  No impact on product safety, identity, strength, purity and quality
 Minor GMP non-compliance
 No impact on patient safety (defects which do not pose any
significant hazard to health, for example cosmetic defects)
(Explanation: A lesser deviation from the requirements which calls for
moderate action)
Medium  Likely impact on product safety, identity, strength, purity and quality
 Major GMP non-compliance
 Potential impact on patient safety (defects which could cause
illness or risk to health, but are not life-threatening, serious or are
medically reversible) Explanation: Noticeable impact on product
quality/patient safety, but is addressable)
High  Direct impact on product safety, identity, strength, purity and quality
 Critical GMP non-compliance – has direct impact on product quality
 Critical impact on patient safety (defects which are potentially life-
threatening or could cause serious risk to health) Explanation:
Definite impact on product quality/patient safety)
Note: Wherever there is a product quality issue based on OOS result that may potentially result in patient harm, the
Severity assessment shall be supported with a Health Hazard Evaluation (HHE) Report.
B) Assessment of Probability of Occurrence of the cause(s)

of the PQC
• The cause of a PQC shall be reviewed to determine the “Probability of
Occurrence” of the PQC in the future.
• The Site PQC Coordinator shall assign a rating (that must be

approved by the Site Quality Head) for the Probability of Occurrence
according to Table B (refer next slide)

Table B: Probability of Occurrence – Rating and Criteria
Risk Rating Criteria

Low The quality related event is unlikely to occur (i.e., it has not occurred
in the past)
Medium The quality related event may occur (i.e., it has occurred infrequently
in the past)
High The quality related event is likely to occur (i.e., it has occurred in the
past on a frequent basis)
Note:
Definitions of “past” and “frequent” for calculation of Probability of Occurrence of PQCs shall be
customized by considering at a minimum, the actual frequency of occurrence of such events.
These definitions shall be captured in specific site/regional procedures.
Example: In case of Product PQCs, if a site receives an average of 15 PQCs in a year, “past” may
be defined as: “1 year” and “frequent” may be defined as “more than 2 PQCs”. However, if the
same site receives an average of 600 PQCs in a year, it is more logical to define “past” as “3
months” and “frequent” as – “more than 50”.
(Please note: this example is only for the purpose of illustrating the logic to be used to frame the
definition of “past” and “frequent”– this should not be considered as a standard for the
definitions).
Assigning Level of Risk Based on “Severity” and “Probability of Occurrence”.
Upon assessing the “Severity” and “Probability of Occurrence” of the PQC, the
Site PQC Coordinator shall assign risk level as shown in Table C.
Note: Severity (i.e. the impact on the patient/product quality) carries a higher
weight than Probability of Occurrence:

Table C: Risk Level based on Severity & Probability of Occurrence
Risk Rating based on Probability of Occurrence

Low Medium High Not
Applicable
High Level ONE Level ONE Level ONE Level ONE
Medium Level TWO Level TWO Level ONE Level TWO

Risk Rating based on
Low Level THREE Level THREE Level TWO Level THREE

Severity
Not Level THREE Level THREE Level TWO Not

Applicable Applicable

C) Assessment of the Probability of Detection (“State of Control”) of the PQC:
• The purpose of this stage in the risk assessment process is to determine if there
are sufficient controls to ensure that the PQC can be recognized or
detected and prevented from recurrence.
• The PQC may have occurred due to a lapse in the application of existing
controls or may be due to the absence of sufficient controls.
• The Site PQC Coordinator (QA) shall assess the state of controls surrounding
PQC and assign a rating as per Table D below:

Table D - Probability of Detection (State of Controls) – Rating and
Criteria
Rating Criteria

The Quality System has either “weak” or “no” controls to detect the quality related event
after its occurrence and prevent it from recurring (e.g. systems are non-validated or with
perception based evaluation techniques, process controls are dependent on human
efficiency, etc.). There is a low chance the current controls will detect the quality event
after its occurrence.
WEAK Explanation:
 There is little to no chance that the patient will detect the quality issue after its
occurrence
 Faults will be passed (to the patient) undetected. Quality System has weak controls
to detect the quality related event after its occurrence and prevent it from recurring
(e.g., systems are not validated)
The system has controls and will possibly detect the quality related event after its
occurrence
Explanation:
 Patient will possibly detect the quality issue after its occurrence
MEDIUM  Some faults may be detected; several coincident faults may go undetected
 Quality system has controls and will possibly detect the quality related event after
its occurrence and avoid it from recurring (e.g., Statistical Process Control is used in
the process, but the product undergoes final inspection off-line)

Table D - Probability of Detection (State of Controls) – Rating and Criteria
The system has multiple controls and is very likely to

detect the quality related event after its occurrence
Explanation:
 Patient is very likely to detect the quality issue after
its occurrence
 Fault will be caught certainly or most certainly
STRONG  Quality system has multiple controls and is very likely
to detect the event after its occurrence and prevent it
from recurring (e.g., 100% automatic inspection with
regular calibration and preventive maintenance of
the inspection equipment, validated systems having
multi-level checks, alarm systems/direct
measurement techniques to monitor faults)

Final Risk Classification (TABLE : E)

Using the results of the Risk Assessment process as described in the earlier section to identify
the level of risk based on the Severity and Probability of Occurrence of the quality issue and
corresponding State of Controls, the Site Quality Head shall perform the final risk assessment
and classify it as Critical/Major/Minor based on Table E and forward to CQC for review, as
deemed necessary:
Rating - Probability of Detection

Not
Strong Medium Weak
Applicable

Level based on Severity and Probability
Level One Major Critical Critical Critical

Level Two Minor Major Critical Critical

Level Three Minor Minor Major Major
Occurrence

of
Unclassified Unclassified Unclassified Unclassified
Not Applicable (NA)


Note: The risk level determined through this matrix may be upgraded to a higher
level, if needed, based on a case-to-case evaluation by QA. If Severity, Probability
of Occurrence and Probability of Detection of a PQC are deduced to be “Not
Applicable” (Example: Alleged Lack of Effect (LOE), PQC received for non-Sun
Pharma products, etc.), the Risk Category shall be concluded as “Unclassified”.
• An example template for determination of Risk Category (Risk Assessment

Matrix) is provided as Attachment III.
• Based on the Validity Assessment of the PQC and the Risk Assessment, if
required, the Site PQC Coordinator shall request the Site Quality Unit to put
impacted batches on hold, as required.
• If the PQC Risk assessed results are determined to be “Critical”, the due date
for PQC closure shall be calculated as follows: Due Date for PQC Closure = Date
when Risk Assessment is completed + ten (10) calendar days.
•

ATTACHMENT III
Risk Assessment Matrix for Product Quality Complaints
(Example Template)

• If the PQC Risk assessed results are determined to be “Critical”, the due date
for PQC closure shall be calculated as follows:
Due Date for PQC Closure = Date when Risk Assessment is completed +
ten (10) calendar days.
• If the PQC Risk assessed results are determined to be “Major or Minor”, the
due date for PQC closure shall be calculated as follows:
Due Date for PQC Closure = Date when PQC Record was opened +
forty (40) calendar days.
• Time extensions for closure of PQCs may be requested when necessary and
shall be approved by the Site Quality Head.

• The PQC risk management action plan shall be dependent on the risk
category and in alignment with the current version of the GQS No.:
QS000068 - Quality Risk Management.
• Based on the results of the Risk Assessment, if needed, the Site PQC
Coordinator shall recommend to the site Quality Unit to initiate a Recall
Proposal for the affected batches of the product; refer GQS No.:
QS000056 - Post Marketing Surveillance and Recalls.
• PQCs, assessed to be “Critical” in terms of patient safety, shall be

specifically reviewed for the need to initiate a product recall.

QUALITY INVESTIGATION OF PQC & ROOT CAUSE IDENTIFICATION
• Each PQC shall be investigated mandatorily to identify the root cause. If

however, a previous investigation exists for the same nature of PQC, it may be
cross referenced and in such case, a new investigation record is not needed to
be initiated.
• The investigation procedures used shall follow the written procedures as

described in the current version of the GQS No: QS000046 – Investigations.
• Sites shall establish procedures for actions related to critical complaints, for
assigning priority to critical investigations related to these complaints, for
performing an assessment of the investigations, for immediate corrective action
taken, for closure of the investigation and for review of CAPA effectiveness.
(Refer to the current version of GQS No.: QS000042 – Handling of Corrective
and Preventive Actions (CAPA)).

• Investigations of PQCs related to CMOs/Contract Packaging

Organizations/Re-Packaging Sites shall be carried out by the contract
manufacturers/packagers.
• The Sun Pharma CMO-QA/RP Regional Quality group (as relevant)

shall review and file the external investigation report provided by the
contract manufacturer’s packagers.

• The Site/CMO- QA PQC Coordinator shall initiate investigation of the

PQC and shall identify a cross-functional investigation team and the
investigation Team Lead based on the nature of the PQC and the
process stage from where the product quality complaint likely originated.
• All the departments involved where the defect may have occurred in
process shall be represented on the investigation team.
• The investigation Team Lead shall be responsible for appropriate

management of and timely completion of the investigation and
preparation of the Investigation Report.
• For trending purposes, similar types of PQCs received in past shall be

reviewed while investigating a PQC.

Handling of PQC Samples

• The Site PQC Coordinator shall • The sample shall be labeled at a
arrange for verification of the minimum with the following
suitability of PQC samples received information:
for testing based on physical PQC ID, Sample Receipt Date, Received
evaluation of sample integrity. By (Name/Sign/Date), etc. and stored
securely in conditions recommended for
the respective product until the PQC is
• Any obvious signs of abuse, closed.
mishandling, improper storage or
tampering shall render the sample • Samples shall be stored until
unsuitable for testing and this one year past the expiration date
determination shall be recorded in where further investigation may
be required. Controlled
the PQC record.
substance samples shall be
securely stored according to
relevant control procedures.

• Based on the nature of the PQC,
- the Site/CMO PQC Coordinator shall request QC to

carry out a physical evaluation and/or testing for
chemical/microbiological attributes of the PQC samples
and/or retain samples of the same batch as required.
• If the outcome of the analysis reveals an OOS result, then

an OOS record shall be created and a cross reference
made to the source PQC-Record.
• Similarly, the OOS record shall cross reference the PQC-

Record unique identifier.

• Documents pertaining to the nature of the PQC shall be

reviewed as part of investigation.
Examples include (but not limited to):
Incoming Material Receipt & Release Records, Alert/Alarm

Records, Manufacturing Records, Packaging Records, Finished
Product Release Data, Equipment Operation Logs, Maintenance
Logs, Repair Logs, Calibration Records, Environmental Monitoring
Records, Deviations/Change Control Records, Stability Data, PQC
Sample Inspection/Testing Results, Retain Sample
Inspection/Testing Results, Product Storage Records, Transit
Records (data logger data, shipment details), Utility (water, steam,
compressed air) Records.

• Any additional information and/or samples received during the process of

investigation shall be evaluated and where necessary, the investigation
revised to reflect current information.
• A detailed impact assessment shall be carried out if the quality issue is

confirmed during investigation of the PQC to evaluate similar batches of the
same product and batches of other products for presence of similar defects.
• In case of drug substances, other batches which may contain re-work of the
defective batch shall be investigated.
• For PQCs received for product(s) which have been re-packaged at contract
re-packaging sites, the investigation may be extended to the original
manufacturing location of such product(s) based on the PQC information.

• The Site PQC Coordinator may • Post investigation completion,

also request the RP - PVG or the Site PQC Coordinator, in
designee to perform a Health conjunction with QA, shall
Hazard Evaluation of the PQC, if review the Risk Assessment
needed, based on the nature of that was carried out before the
PQC (e.g., medical association), investigation and if needed,
regulatory requirements, outcome may request the CQC to
of quality investigation, etc. recalculate the risk category.
• Health Hazard evaluation is • In case of a change in the risk

mandatory in case PQC Quality category, the revised risk
investigation reveals OOS result. category shall be documented
in the amended PQC record.
PQCs, assessed to be “Critical” in terms of patient health and safety post-

investigation, shall be specifically reviewed for the need to initiate a product recall.

The need for notifying the appropriate Regulatory Agency of PQC information during
or after completion of investigation shall be performed according to site procedures
by the RA department.
The Site PQC Coordinator shall submit an extension request with supporting
justification to the Site Quality Head or designee for review and approval in case
the PQC investigation is not concluded within thirty (30) calendar days from date of
initiation.
PQCs Related to Counterfeiting :
Special attention shall be given to investigate whether a PQC is associated with

counterfeiting.

The following steps shall be followed for investigations of PQCs related to

counterfeit drugs:
• Verification and comparison of the PQC sample with retain samples of the
PQC related batch for pack details, such as foils, cartons, printed text,
orientation/alignment of text, lot/batch code accuracy, expiry date accuracy,
etc.
• Testing of PQC sample, if needed
• If investigation findings establish counterfeiting, the PQC sample shall be

sent to the Packaging Development Department for review of the need for
any corrective actions to introduce/improve anti-counterfeit measures in the
pack design.
• PQCs related to counterfeit drugs shall be reported to the relevant

Regulatory Agencies and Sun Pharma’s Legal Department

USE OF PQC CLASSIFICATIONS FOR CAPA
After completion of Investigation, classification of the PQC shall be utilized

by the Site PQC Coordinator to plan and prioritize appropriate CAPA.
Examples related to the risk classifications follows :
Critical: PQCs related to drug substance(s) or drug product(s) having potentially
life threatening consequences shall be termed as “Critical”.
For Example:
Drug Products:
Quality Defect that is likely to cause AE/ Efficacy issues which may have life-
threatening consequences (e.g. any extraneous matter in injectable and ophthalmic
products, extraneous matter in non-injectable/ non- ophthalmic products with life-
threatening consequences (such as metal, glass, etc.) and wrong product (label and
contents are different), correct product, but wrong strength with serious medical
consequences, product mix-ups.
Drug Substances:
Abnormal impurity levels, product mix-ups, wrong product (label and contents are
different).
Major: PQCs related to drug substance(s) or drug product(s) that could

cause illness or health issues are termed as “Major”.
For Example:
Drug Products: Drug Substances:
Quality defects which are likely to Failure in chemical/physical

cause AE/efficacy issues that are, attribute of the product, significant
however, not life threatening or drop from reported assay values,
serious ones or are medically packaging issues, such as
reversible, wrong/missing text or wrong/missing text or figures
figures which may affect the product which may affect the product
identity/usage instructions (e.g. identity/usage instructions (e.g.
missing or incorrect missing or incorrect
manufacturing/expiry date, missing manufacturing/expiry date),
leaflets or leaflets with incorrect presence of extraneous matter,
information), significant shortages, etc.
etc.

Minor: PQCs related to drug substance(s) or

drug product(s) having consequences that may
not pose a significant hazard to health are termed
as “Minor”.
For Example: A faulty closure that will not result in

any medical or health consequences, insignificant
shortages, faulty secondary or tertiary packaging,
that will not, however, affect the product quality,
poor/improper presentation of product containers,
quality defects which are likely to cause efficacy
issues, but will not cause any significant hazard to
health.
Unclassified (i.e. alleged Lack of Effect (LOE) due to customer perception,

PQC received for non-Sun Pharma products).
Note: The categorization examples used in this section are provided for illustration only
and are not meant to be all inclusive.
QA SUMMARY & CONCLUSION FOR PQC
• Once the root cause has been identified and classification of the PQC
post-investigation completed, the Site/CMO PQC Coordinator shall
evaluate and summarize the investigation findings and prepare a
conclusion related to the PQC.

• Based on the investigation and the conclusion(s) drawn, recall of the
affected batches of the product shall be considered.
• All PQCs, assessed to be “Critical” in terms of patient safety post-

investigation, shall be reviewed to determine the need to initiate a
product recall. (Refer to the current version of GQS No.: QS000056 –
Post-marketing Surveillance and Recalls).

CAPA GENERATION & MANAGEMENT
• Based on the root cause(s) identified as an outcome of the investigations,

the Site/CMO PQC Coordinator shall initiate CAPA for all PQCs, except
when a CAPA for a similar event has already been identified and
implemented or for other reasons that can be justified using supporting
rationale based in science.
• Documented justification shall be mandatory and included with all PQC

records, where CAPA is not being initiated.

• CAPA process shall be implemented following the written procedures as
described in the GQS No.: QS000042 - Handling of Corrective and
Preventive Actions (CAPA).

• The Site PQC Coordinator and the Site CAPA Coordinator shall monitor
effective implementation of CAPA related to PQCs.

RESPONSE REPORT TO COMPLAINANT AND CLOSURE
OF PQC:
Based on the investigation findings, a PQC Response

Report shall be prepared by the Site PQC Coordinator.
This Report shall be further reviewed and approved by
the Site Quality Head/designee.
An example template for the PQC Response Report is

provided as Attachment IV.
After the Response Report has been approved by the

Site QA Head/designee, it shall be sent to the PQC
Initiator or designee who shall forward it to the
Complainant.

ATTACHMENT IV

Interim Response
RESPONSE REPORT Reports may be sent as AND
TO COMPLAINANT necessary or if
CLOSURE OF PQC:
requested by the Complainant.
Filing of an Interim Response Report is required when
PQC investigations cannot be closed within 10 calendar
days for “Critical” or 30 calendar days for “Major” or
“Minor” events.
Supporting rationale for the delay in closing the

investigation shall be documented in the PCR Record.
The final Response Report shall be shared with the
Complainant after conclusion of investigations.
Closure timelines for PQCs shall be according to risk

assessments as described in steps 7.4.7 and 7.4.8(slide
50).
Delays in closure shall include documented justifications
in the PQC record by the Site PQC Coordinator.

RESPONSE REPORT TO COMPLAINANT AND CLOSURE OF PQC:
A PQC report shall be considered “closed” in cases

when sending a completed Response Report is not
possible (e.g., the complainant address is not known).
After sending the Response Report to the Complainant, if

further communications regarding the same PQC are
received, they shall be responded to, by the Site PQC Initiator
or designee.
If needed, the Site QA Head or designee, may, at a later
date allow the PQC investigation to be re-opened and/or
the conclusion to be revised, as required.
A PQC may also be re-investigated/reviewed if the
Complainant provides any additional information or
additional samples regarding the PQC.
PQC closure shall be independent of closure of CAPA
and/or Product Recall (if initiated). However, if OOS
records have been created as an outcome of the PQC
investigation, they shall be verified for closure before
closing PQC.

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TREND ANALYSIS OF PQC:
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© Sun Pharmaceutical Industries Limited. All Rights Reserved.
RETENTION OF PQC RECORDS :
PQC records shall be preserved for the

retention periods as mentioned per the
regulatory requirements or in the current
version of the GQS No. QS000065 -
Documents and Records.

REQUIREMENTS
Site Quality Head shall establish and maintain a PQC procedure to

investigate and document PQCs in a timely manner that includes, but is not
limited to, the following information:
A. Justification and validity of the PQC

B. Scope of the PQC (sample, lot, other lots)
C. Evaluation of the impact on other lots, other products, performance in the
field or production processes
D. Nature of the PQC, i.e., aesthetic, functional (ability to use the product),
efficacy and/or safety.
Corporate Quality Compliance shall review and approve the PQC handling
system and shall ensure the following but not limited to: that there is a control
system that is approved by Corporate Quality Compliance, that procedures
are established, that procedures are followed, that procedure meet
compliance expectations and that performance of the system is measured and
improved where possible.

REQUIREMENTS
The PQC handling procedure shall include a requirement for the investigation and
evaluation of the manufacturing process, quality systems, environmental conditions
(if appropriate) and related lots of product. When a PQC involves a medical device,
servicing records for that device shall be investigated.
Each Site and Market Company shall establish and maintain procedures to assure
the results of an investigation that might lead to a market place withdrawal, field
alert, early warning, rapid alert or recall are identified and reported within the
required notification period.(Refer to current version of the GQS No.: QS000055 -
Filed Alert Report (FAR)).

REQUIREMENTS
PQCs involving an adverse event shall be reported to

Pharmacovigilance.

PQCs and results of the investigations shall be evaluated
for trends, systemic quality issues and cross regional
issues by Corporate Quality - Compliance.

All PQC reports shall be submitted to the CQC. There shall
be a final consolidation of all PQCs at the Corporate
Quality Compliance level to provide a worldwide view of all
PQCs.

REQUIREMENTS
Documentation requirements for the investigation of a PQC shall be pre-defined

and shall include, but not be limited to, the following information:
1. A unique identifier assigned to each PQC Record.

2. Name of Initiator (RP or designee) and date PQC Record was opened.
3. Date of receipt of PQC at Sun Pharma.
4. Market where PQC originated
5. Product details (name, strength, dosage form)
6. Lot number
7. Package size (if applicable)
8. Name and contact information of complainant
9. Short description about the nature of the complaint and extent of the alleged
problem found
10. The impact on the patient, if applicable. Batch Number(s) as reported by
Complainant (The RP shall indicate in the record cases where the PQC batch
number is not available at the time of logging in the PQC).
11. Quantity and condition of returned PQC samples (if applicable)
12. Steps taken to conduct the investigation
13. Investigation conclusion including a justification of the conclusion
REQUIREMENTS
An assessment of the impact of the PQC on product being manufactured and of

product in the field shall be performed and documented as part of the investigation
plan. Records for the investigation of a PQC related to a device shall include a
determination of the following:
A. Whether the device failed to meet specifications.

B. Whether the device was being used for treatment or diagnosis.
C. The relationship, if any, of the device to the reported incident or adverse
event.
For devices, if a manufacturer's formally designated PQC unit is located outside the
United States, PQC files shall be reasonably accessible in the United States either at
the location in the United States where the manufacturer's records are regularly kept
or at the location of the initial distributor.

REQUIREMENTS
Attachment I - PQC Acknowledgement Report (Example Template)

(Form No.:
QS000049/01/00)
Attachment II -Product Quality Complaint Validity Logic Matrix (Form
No.:
QS000049/02/00)
Attachment III -Risk Assessment Matrix for Product Quality Complaints
(PQC)
(Example Template) (Form No.: QS000049/03/00)
Attachment IV -PQC Response Report (Example Template) (Form No.:
QS000049/04/00)

Thank You!
For more information please contact:
Corporate Quality, GxP
Thank You
Training/Certification & Communication
Department
CQGXP.Training@sunpharma.com
© 2010 Sun Pharmaceutical Industries Limited., All Rights Reserved.

“SUN Pharma”, The Sun Pharmaceutical Industries Logo are trademarks of Sun Pharmaceutical Industries Limited.
This material was used during an oral presentation; it is not a complete record of the discussion. This work may
not be used, sold, transferred, adapted, abridged, copied or reproduced in whole on or in part in any manner or
form or in any media without the prior written consent. All product names and company names and logos
mentioned herein are the trademarks or registered trademarks of their respective owners.

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PRODUCT QUALITY COMPLAINTS

 Please keep your phone in “mute” while

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 2

This Global Quality Standard

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 3

Contract Manufacturing Organizations (CMOs)

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 4

• Processing of PQC shall be CMOs

• Accountabilities of Sun Pharma and CMO in

 Site Specific SOPs shall not ignore any point /

 Sites shall prepare or revise their existing site specific

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 6

Quality issues reported prior to distribution of the

PQCs related to IMP / batches used for Clinical

EACH MARKET COMPANY

Forwarding PQCs to Communicating

Assuring each Market Company is qualified to handle the

Assuring there is a system for receiving and documenting PQCs,

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 9

Evaluating on a routine and regular

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 10

• Notifying Pharmacovigilance(PVG) when an adverse

• Assessing whether an AE/LOE/Efficacy related PQC

• Investigating, testing, resolving, documenting and closing

• Performing Risk Assessment and classification of PQCs.

• Defining and implementing corrective and preventive

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 11

• Notify CQC of any adverse event on monthly basis through

• Notifying the Site QA or designee of any adverse report that

• Assessing whether the PQC is associated with any AE, LOE

• Performing Health Hazard Evaluations where applicable.

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 12

• Regulatory Agency notification of PQCs as required

1. Additional responsibility detail is provided in the process

2. Responsibilities in this GQS are suggested based on

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 13

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 14

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 15

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 16

WORKFLOW Receipt & Logging of PQC by Responsible Person / Initiator *

Sending of Acknowledgment Report to Complainant

Follow either Step A 1 or Step A 2

Forwarding of PQC to Forwarding of PQC to Notification to RP, as needed

Validity Assessment of PQC by PVG Validity Assessment: Yes

PQC concluded as ‘Invalid’ by Site

Product Recall Proposal, Closure of PQC as ‘Closed-Invalid‘

HHE from PVG, if required

Root Cause Identification (In) QC Testing of Samples, if required

Sending of Response Report to complainant totoCCCCComplainant

Note: Dotted Lines Indicate Optional activities

Closure of PQC PQC

Re-Activate to Re-Activate to Update Conclusion

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 17

Management of PQCs shall be carried out

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 18

PQC information received by written, electronic or oral

• Note: Each Market Company, Licensee, Contract

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 19

• Each PQC Record shall be assigned a unique identifier for traceability.

• Any impact on health or safety reported by a reporter (consumer or

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 20

• Contact information for Primary source of the PQC.

© Sun Pharmaceutical Industries Limited. All Rights Reserved. 21

• PQC records shall be created preferably on the day of receipt but