Reference Guideline Definitions GMP Requirement: 21 CFR § 211.198 and ICH Q7 Procedure for Handling of Complaints Complaint Investigation Remedial action and CAPA Report preparation Response to customer Verification of CAPA effectiveness Review of Complaints

1. HANDLING OF CUSTOMERS COMPLAINT
Dr. A. Amsavel

2. OVERVIEW
 Reference Guideline
 Definitions
 GMP Requirement: 21 CFR § 211.198 and ICH Q7
 Procedure for Handling of Complaints
 Complaint Investigation
 Remedial action and CAPA
 Report preparation
 Response to customer
 Verification of CAPA effectiveness
 Review of Complaints

3. GUIDELINES/ REQUIREMENTS
 21 CFR § 211.198 Complaint files.
 Investigation according to 21 CFR § 211.192 Production
record review & Record and Reports shall be available
§ 211.180(c).§ 211.180(c).
 Field Alert Report Submission Questions and Answers
Guidance for Industry July 2018
 ICHQ7 GMP for API: Section -15 Complaints and
Recalls

4. DEFINITION
Correction: An action to eliminate a detected
nonconformity. ie Remedial action, Reprocess, rework, or
adjustment
Corrective Action: The action taken to eliminate the causesCorrective Action: The action taken to eliminate the causes
of an existing nonconformity, defect or other undesirable
situation in order to prevent recurrence.
Preventive Action: The action taken to eliminate the cause
of a potential nonconformity, defect, or other
undesirable situation in order to prevent occurrence.
4

5. DEFINITION
 Conforming: Fulfillment of a requirement. An expected
observation, event or characteristic.
 Nonconforming Material or Process (Discrepancy) : Any
material or process that does not meet its required
specifications or documented procedure.specifications or documented procedure.
 Nonconformity: Non-fulfillment of a specified requirement.
(Any material or process that does not meet its required specifications
or documented procedure).
 Complaint : Customer / consumer reporting on the
product or service, due to non-confirming of product or
process or service. It may be related to quality, packing,
document, service, etc.
5

6. DEFINITION
Field Alert Report (USFDA)
Any incident that causes the drug product or its labeling
to be mistaken for or applied to another article,
bacterial contamination, a significant chemical, physical,bacterial contamination, a significant chemical, physical,
or other change, deterioration in the distributed drug
product, and failure of one or more distributed batches
of the drug product to meet the specifications
established in its application
I

7. PURPOSE OF COMPLAINT HANDLING
 To ensure the patient safety.
 To meet Regulatory Requirement
 To maintain cGMP
To maintain relationship with customers To maintain relationship with customers
 It is reputation of company
 It is an opportunity to improve the quality of the
product or service
 To improve the business growth

8. 21CFR § 211.198 COMPLAINT FILES
 Procedures shall be established and followed for handling
of all written and oral complaints regarding a drug product
 Any complaint involving the possible failure of a drug
product to meet any of its specifications need for an
investigation in accordance with § 211.192.investigation in accordance with § 211.192.
 Review to determine whether the complaint represents a
serious and unexpected adverse drug experience which is
required to be reported to the Food and Drug
Administration

9. 21CFR § 211.198- COMPLAINT FILES.
 A written record of each complaint shall be maintained at
the site and readily available for inspection
 Written records related to complaint shall be maintained
until at least 1 year after the expiration date of the druguntil at least 1 year after the expiration date of the drug
product, or 1 year after the date that the complaint was
received, whichever is longer.
 For OTC drug products records shall be maintained for 3
years after distribution of the drug product.

10. 21CFR § 211.198- COMPLAINT FILES
 Record shall include the following information, the name
and strength of the drug product, lot number, name of
complainant, nature of complaint, and reply to
complainant.
 Record of Investigation conducted, and findings and Record of Investigation conducted, and findings and
follow-up.
 The record of the investigation shall be maintained
 If investigation is not conducted, record the reason for an
investigation was not necessary and the name of the
responsible person making such a determination.

11. ICH Q7: 15.0 COMPLAINTS AND RECALLS
All quality related complaints, whether received orally or in
writing, should be recorded and investigated
Complaint records should include;
 Firm, Name, title , phone number, address of the complaintant
 Date complaint is received Date complaint is received
 Complaint nature (Product & batch number of the API)
 Immediate Action taken if any (dates & action taken by the person)
 Investigation & CAPA
 Response provided to the originator of complaint with date
 Final decision / Conclusion
 Follow-up action taken

12. ICH Q7: 15.0 COMPLAINTS AND RECALLS
 Records of complaints should be retained in order to evaluate trends,
product related frequencies, and severity with a view to taking
additional, and if appropriate, immediate corrective action.
 There should be a written procedure that defines the circumstances
under which a recall of an intermediate or API should be considered.
 The recall procedure should designate who should be involved in
evaluating the information, how a recall should be initiated, who
should be informed about the recall, and how the recalled material
should be treated.
 In the event of a serious or potentially life-threatening situation, local,
national, and/or international authorities should be informed and
their advice sought.

13. PROCEDURE FOR HANDLING OF COMPLAINTS
 SOP for investigation and reporting the market complaints
should cover the following, but not limited to
 Purpose, Scope, Responsibility & Authority
 Cover all quality-related or other complaints, whether received
orally or in writing, is being recorded and investigatedorally or in writing, is being recorded and investigated
 Record the receipt of the complaint in complaint log book
 Acknowledge the receipt of complaint (timeline eg within 24hrs)
 Classify on nature of complaint. eg. Product quality ,
Packaging, Document, Label etc
 Categorize as Critical / Major / Minor

14. PROCEDURE FOR HANDLING OF COMPLAINTS
 Containment of complaint batch , if required
 Investigation of complaint based on the complaint nature.
Testing of reserve sample, review of manufacturing and test
records, Equipment, calibration, facility, environment etc ..
 Time period for investigation Time period for investigation
 Content of Investigation report and response to customer
 If complaint is not genuine or send response with justification
 Remedial action and CAPA as appropriate
 Closing of complaint
 Review of effectiveness
 Maintain the compliant records

15. COMPLAINT INVESTIGATION
 Record the receipt of the complaint in complaint log book
 Complaint number & Date of complaint received
 Details of organisation/person, title, address, contact of complainant
 Product name, Batch number, quantity and date of supply
 Nature of Complaint: Quality , packing, document error, label etc
 Category - Critical/ Major/ Minor Category - Critical/ Major/ Minor
 Containment of material, if stock is available from the complaint
batch at warehouse.
 Time period for investigation and response to customer
 If it is critical (life threaten) send response within 2-5 days to contain /
action at customer end, and investigation can be continued
 Other than critical 2-4 weeks
 Interim report if investigation required time

16. INVESTIGATION STEPS
1. Define the Complaint
2. Evaluate the Magnitude and Impact
3. Make a Plan for Investigation
4. Identify RCA thorough Assessment
5. Remedial & CAPA plan with tasks
6. Implementation the action plan
7. Follow up /verify the effectiveness
Use investigation tool as required ie. why-why, cause
and effect (fish bone), brainstorm, FEMA etc

17. COMPLAINT INVESTIGATION
 Investigation : Uses check list for review / verification
 Test the reserve sample of the complaint batch. If required test
the previous and subsequent to complaint batches.
 Request sample from customer if required for investigation
and test the sampleand test the sample
 Form the Investigation team: QA, QC, production and if
required ES, R&D and others
 Review the records (details -next slide)
 Identify the root cause or probable cause
 If required visit the customer site for investigation

18. INVESTIGATION: REVIEW OF RECORDS
 Review past history /similar issue & their investigation reports
 Review the following records and documents, but not limited to;
 BPR, cleaning record, test records, trend , change control ...
 OOS, deviation if found
 Review of input material, quality, quantity & vendor
Review process/operations Review process/operations
 Review the situation/ environment
 Review of Systems / facility/ Equipment
 Eg. Environment, Log book, cleaning,, PM, Calibration physical
check etc
 Interview people involved in the manufacturing, sampling & testing
 Gemba-Inspect equipment & facilities at site
 Any additional testing required based on the above

19. COMPLAINT INVESTIGATION
 Review the storage & transportation, if special storage condition
recommended
 Extend the investigation to other batches , other campaign,
other Product / materials, other Equipment / train etc
 Evaluate Product Impact / Disposition Evaluate Product Impact / Disposition
 Provide reason for accept / rejection of the batch based on the
outcome of the investigation.
 Justify the exclusion of other batch if required
 Consider toxicological evaluation if required
 Remedial Action/Correction: Action to address an immediate
problem ie Reprocess/ reworking or can be taken in conjunction with
CAPA

20. COMPLAINT INVESTIGATION REPORT
 Prepare the Complaint Investigation report with the following details, but
not limited to,
 Complaint number & Date of complaint received
 Details of organisation/person, title, address, contact of complainant
 Product name, Batch number, quantity and date of supply
 Nature of Complaint: Quality , packing, document error, label etc
 Category - Critical/ Major/ Minor Category - Critical/ Major/ Minor
 Immediate action taken (with date & name of person taking the action)
 Investigation report with root cause or most probable cause
 Remedial action or correction
 Corrective action and preventive action if possible
 Conclusion & Recommendation to customer if required
 Decision on recall, if complaint is serious or potentially life-threatening
situation.

21. RESPONSE TO CUSTOMER
 Information to regulatory agencies if complaint is serious or
potentially life-threatening situation.
 Submit the investigation report to customer as per time line
specified in the SOP and based on the nature of complaint.
 In case the investigation require additional time, provide
interim report and get extended time with justification.
 The complaint shall be closed based on the acceptance of the
response from the customer and assessment of CAPA.
 In case the customer is not responding within 2-3 weeks send
the reminder for feedback; if customer is not responding,
inform as complaint is closed.

22. COMPLAINT VERIFICATION & RECORDS
 Verify the implementation of correction and CAPA for its
effectiveness.
 Review the complaint periodically (may be monthly or
quarterly) to determine if there are any unfavourable
trends in the complaint data.trends in the complaint data.
 Review all the complaints in the management review
meeting
 All complaints shall be reviewed and reported in APQR
 Complaint records shall be maintained at least one year
after retest date of API or expiration date of drug product

23. RECALL
 Decision on recall, if complaint is serious or potentially life-
threatening situation.
 Information to local, national, and/or international authorities
should be informed and their advice sought.
 Initiate the recall as per procedure should designate who Initiate the recall as per procedure should designate who
should be involved in evaluating the information,
 Who should be informed about the recall, and
 How the recalled material should be treated.

24. Thank YouThank You
Dr. A. Amsavel