sop for Handling of Deviations
1.0 OBJECTIVE :
1.1 To lay down a procedure to describe the requirements to ensure that the events that could impact, directly or indirectly, the identity, strength, efficacy, quality, safety, potency or purity of materials and products are investigated, reviewed, documented and reported in a timely and standardized manner.
Investigation of deviations is a portion of the overall Quality Program and appropriate response to deviations is an important component of continuous improvement activities.
1.2 The objective of deviation management is to define the root cause of deviation occurrence and to develop and effectively implement timely corrective and preventive action(s) to eliminate recurrence of the deviation
2.0 SCOPE :
2.1 This procedure is applicable whenever an event occurs that represents a departure from current Good Manufacturing Practices, Standard Operating Procedures, manufacturing or operating instructions, test plans or instructions, applicable regulations or standards or emergence of an adverse trend at ABC Pharma Pvt. Ltd.
3.0 RESPONSIBILITY :
3.1 Deviation initiating department shall be responsible for reporting deviation along with reason for deviation.
3.2 Executive/Manager of deviating department shall be responsible to:
3.2.1 Act in a timely fashion to limit the exposure of product involved with deviations.
3.2.2 Train and encourage staff to be vigilant in preventing, recognizing and reporting deviations.
3.2.3 Assist in formulating investigation plans, conducting investigations, implementing corrections
and completing the required documentation associated with deviation situations.
3.2.4 At the time of investigation, record all facts and details relevant to the occurrence of the deviation and ensure that product or material in “QA Hold” status and are not use till further QA intimation.
3.3 Dept. Head shall be responsible for ensuring the implementation of approved corrective and preventive actions and inform the same to QA.
3.4 Officer/Executive/Manager QA shall be responsible to quarantine the product or materials affected by a deviation until conclusion of required investigation(s) and a disposition decision has been rendered.
3.5 Manager/Head QA shall be responsible to conduct a quality review of all the deviation documentation to verify a complete root cause analysis, risk assessment and corrective and preventive action(s) are performed and documentation is correct.
3.5.1 Executive/Manager QA shall be responsible to maintain a trend analysis to evaluate and assess all deviations. Report trends and emerging quality problems identified through appropriate metrics
3.6 QA Head shall be responsible for reviewing and approving/rejecting deviation looking into the impact of proposed deviation.
4.0 ACCOUNTABILITY: Concern Department Head / QA Head.
5.0 PROCEDURE:
5.1 There are two types of Deviation;
5.1.1 Planned Deviation
5.1.2 Unplanned Deviation (unforeseen deviations, non – conformances)
5.2 Planned Deviations (Planned Deviation Report)
5.2.1 Any Deviation in manufacturing process / procedure / testing procedure / operating / calibrating procedure, batch size, equipment, operating environment or any other GMP critical process which is pre-planned for the forthcoming batches, shall be known as planned deviation.
5.2.2 Such a pre-planned deviation shall be taken / implemented only after pre-approval from QA.
5.2.3 Such planned deviations shall be properly documented, assessed / evaluated for its impact on product quality and authorized by QA in advance.
5.2.4 All planned deviations shall be recorded as per Annexure-1.
5.2.5 QA shall maintain a logbook for the approved planned deviations as per Annexure- 2.
5.2.6 The concerned department officer / executive / manager shall initiate the “Planned Deviation Format” by documenting the following and signing off;
Product Name
Batch Number
Market (if applicable)
Batch Size
Manufacturing Date
Expiry Date
Deviation related to (procedure, process, equipment, standard, batch size, batch yield etc.)
Deviation details
Justification / Rationale
Supporting Data
5.2.7 The department head / Nominee and Director shall review the proposal for planned deviation, justification given for its potential impact on the product quality and compliance to regulatory requirements, for necessity / feasibility of the deviation and Sign off in the specified columns.
5.2.8 QA shall assign a unique number to each planned deviation report as follows;
5.2.8.1 The reference number for an planned deviation report shall consist of ten (10) alphanumeric characters.
5.2.8.2 For example, PDR/19/001 shall be assigned to the first planned deviation of year 2019.
5.2.8.3 In the report number for planned deviation, the 1st, 2nd & 3rd characters ‘PDR’ Stands for ‘Planned Deviation Report’.
5.2.8.4 The 4th character “/” is a forward slash.
5.2.8.5 The 5th & 6th characters ‘06’ represent the last two digits of the year 2019.
5.2.8.6 The 7th character “/” is again a forward slash.
5.2.8.7 The 8th, 9th & 10th characters ‘001’ are a sequential serial number.
5.2.9 Head QA shall approve/reject the Planned Deviation with appropriate recommendations.
5.2.10 If approved, the deviation shall be applicable for a defined number of batches or defined number of days, as mentioned in the Planned Deviation Report.
5.2.11 After QA approval, the concerned department shall implement the planned deviation and the observations and data generated shall be documented.
5.2.12 QA shall review the implementation and make sure that the recommendations are complied with quality profile of the batches impacted by the deviation are studied and all the data is annexed with the “Planned Deviation Report Format”.
5.2.13 The closure of the planned deviation shall be responsibility of the operating manager and QA manager.
5.2.14 Recommendations may be made during the review.
5.2.15 If the planned deviation in the process / procedures, leads to improvement in the product quality / process / assurance / GMP, then the deviation / change can be made permanent by following the change control procedure.
5.2.16 Finally, Plant Head/Director and QA Head shall sign off the closure in the specified columns.
5.3 Unplanned Deviations (Unplanned Deviation Report)
5.3.1 While carrying out day-to-day activities, there are chances of unplanned deviations (Unforeseen deviations) and events to occur. These deviations are unforeseen, accidental and may be due to several reasons like;
Equipment failures / breakdowns / malfunctioning / Process Failures.
Power supply failures / interruptions.
Accident / Mishap in the plant.
Breakdown in support services / utilities.
Documentation Failures.
Analytical Failures / errors.
Any other unforeseen situation.
5.3.2 An unplanned deviation report (UDR) shall be raised as a part of the approved system for handling of deviations at the time they occur, in order to provide a mechanism for alerting production and quality department to record the deviation and assess the impact and perform corrective action.
5.3.3 All unplanned deviations shall be recorded as per Annexure- 3.
5.3.4 QA shall maintain a logbook for the approved unplanned deviations as per Annexure- 4.
5.3.5 Operator on the job shall inform production supervisor about the details of incident, resulting in deviation in the process.
5.3.6 Production officer / executive shall fill the details of the unplanned deviation in format of Annexure- 5 and forward the same to production head for his review, assessment and comments.
5.3.7 Finally, the ‘Unplanned Deviation Report’ shall come to QA for review and approval.
5.3.8 The numbering of unplanned deviation report shall be done as follows;
5.3.8.1 The reference number for an unplanned deviation report shall consist of ten (10) alphanumeric characters.
5.3.8.2 For example, UDR/19/001 shall be assigned to the first unplanned deviation of Year 2019.
5.3.8.3 In the report number for unplanned deviation, the 1st, 2nd & 3rd characters ‘UDR’stands for ‘Unplanned Deviation Report’.
5.3.8.4 The 4th character “/” is a forward slash.
5.3.8.5 The 5th & 6th characters ‘06’ represent the last two digits of the year 2019.
5.3.8.6 The 7th character “/” is again a forward slash.
5.3.8.7 The 8th, 9th & 10th characters ‘001’ are a sequential serial number.
5.3.9 Head – QA & Head – Production shall assess unplanned deviation for its impact on product quality. Details shall be documented as per Annexure-5.
5.3.10 Head QA may recommend for performing any additional studies, if required.
5.3.11 If the Deviation does not affect product quality, Head – QA shall allow further processing of the batch in question.
5.3.12 If there are likely chances of product quality getting affected, Head – QA shall assess the impact on product quality before allowing further processing of the batch.
5.3.13 Product may be “Quarantined” in sealed containers, if required. Containers shall be labeled, indicating product name, Batch No., Manufacturing Date, Expiry Date & Batch size. The labeled containers shall be kept in secured quarantine area under lock and key.
5.3.14 Head – QA along with the Head – Production & Head – Maintenance shall investigate & find out the root cause of the problem that resulted in the deviation.
5.3.15 Based on the investigation, corrective and preventive action shall be planned to avoid any such reoccurrence and the same shall be implemented.
5.3.16 Head – QA shall inform Plant Head / Director / Head – Production regarding the disposition of the batch under deviation and also shall decide about the requirement of carrying out any additional tests, controls, and sampling and stability studies.
5.3.17 Reprocessed batch shall be kept on stability studies as per ICH Guidelines, in case of major rework.
5.3.18 Reprocessed product shall be released only if the Product meets all the approved specifications.
5.3.19 QA Manager shall review stability data at scheduled intervals to decide further course of action.
5.4 Both planned and unplanned approved deviations shall be controlled by QA and the same shall be documented in the respective BMR and BPR also.
5.5 Closure of Deviation:
5.5.1 Finally, Head – QA shall close the deviation by reviewing and assessing the impact of deviation on the quality of the product.
5.5.2 Any data, comments, documents required to close the deviation (e.g. stability data) shall be recorded or attached to the deviation report.
5.5.3 The Deviation shall be closed within 30 days from date of Initiation. If investigation shall be going to continue for more than 30 days then extension shall be taken by concerned department which shall be Approved from Head QA.
6.0 ABBREVIATION:
| Sr. No. | Abbreviation used | Full form of abbreviation used |
| 1.0 | QA | Quality Assurance |
| 2.0 | SOP | Standard Operating Procedure |
| 3.0 | BMR | Batch Manufacturing Record |
| 4.0 | BPR | Batch Packing Record |
| 5.0 | cGMP | Current Good Manufacturing Practices |
| 6.0 | cGLP | Current Good Laboratory Practices |
7.0 ATTACHMENTS (ANNEXES) :
Annex-I : Planned Deviation Report Format
Annex-II : Logbook for Planned Deviation Reports
Annex-III : Unplanned Deviation Report Format
Annex-IV : Logbook for Unplanned Deviation Reports
Annex-V : Flow Chart for Handling of Planned Deviation
Annex-VI : Flow Chart for Handling of Unplanned Deviation
Annex-VII : Investigation Extension Request Form
8.0 REFERENCE :
| Sr. No. | Reference Title |
| 1.0 | Schedule M (Good Manufacturing Practices and Requirements of Premises, Plant and Equipment for Pharmaceutical Products) |
| 2.0 | Quality assurance of Pharmaceuticals, A compendium of guidelines and related materials, Volume 2 |
| 3.0 | Guide to Good Manufacturing
Practice for Medicinal Products |
Annex-I
Planned Deviation Report Format
| 1.0 | Initiated By (department): | |||||||||||||||||||
| 1.1 | Product/Item/Document name/System/facility: | |||||||||||||||||||
| 1.2 | Batch No./A.R.No./Document No. | Market: | ||||||||||||||||||
| Supplier name, Date of Supply and quantity, In case of Item:
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| 1.3 | Batch Size: | Mfg. Date: | Expiry Date: | |||||||||||||||||
| 1.4 | Deviation related to:
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Environment Control Media Issue Equipment/Instrument Training
Documentation Human Error Raw material/Packing material In process Maintenance Labelling Supply Cross contamination
Quality Observation any other |
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| 1.5 | Description of Deviation:
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| Name of initiator | Signature | Date | ||||||||||||||||||
| 1.6 | Justification for deviation/investigation of deviation with document reference:
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| Name of initiator | Signature | Date | ||||||||||||||||||
| 1.7 | Department Head
(Comment)
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| Name | Signature | Date | ||||||||||||||||||
| 1.8
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Potential Impact Reviewed by QA: | |||||||||||||||||||
| Area Documentation Safety Other Batches Efficiency of maintenance Qualification
Utility Process Hold time study Design Lay out Calibration Analytical Activity Training Other Product Environmental Condition Regulatory Aspect Facility and System Financial Aspect Stability Equipment/Instrument Other (if any): |
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| 1.9
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Intimation of deviation: To be given by QA | |||||||||||||||||||
| Department | Required | Not Required | Comments(Acceptable /Not Acceptable) | Sign/ date | ||||||||||||||||
| QA | | | ||||||||||||||||||
| QC | | | ||||||||||||||||||
| PROD. | | | ||||||||||||||||||
| HR | | | ||||||||||||||||||
| EN | | | ||||||||||||||||||
| WH | | | ||||||||||||||||||
| Any Other | | | ||||||||||||||||||
| 2.0 | Review by Plant Head / Director
(Comments): |
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| Name | Signature | Date | ||||||||||||||||||
| 3.0 | QA Review / Approval | |||||||||||||||||||
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3.1 |
Any additional studies required | Yes / No | ||||||||||||||||||
| Stability Studies Additional Quality Testing Others | ||||||||||||||||||||
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3.2 |
Quality Assurance (comments): |
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| 3.3 | Deviation: | Approved Rejected | ||||||||||||||||||
| 3.4 | The Deviation is limited to time / No. of Batches: | |||||||||||||||||||
| 3.5 | Can the Deviation/Change be made permanent through change control? Yes / No | |||||||||||||||||||
| 3.6 | Review by Head – QA | Name | Signature | Date | ||||||||||||||||
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| 4.0 | Implementation of Deviation | |||||||||||||||||||
| 4.1 | Deviation implemented by (department) |
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4.2 |
Observations (If any): |
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4.3 |
Data Generated (If any): |
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4.4 |
Quality Profile of batches affected (If applicable): |
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| 4.5 |
Implemented ByDepartment Head |
Name | Signature | Date | ||||||||||||||||
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| 5.0 | QA Review of Implementation & Closure | |||||||||||||||||||
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5.1 |
QA comments: |
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| 5.2 | All recommendations fulfilled: | Yes / No | ||||||||||||||||||
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5.3 |
If No, Justification: |
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| 5.4 | Data generation completed: | Yes / No | ||||||||||||||||||
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5.5 |
If No, Justification: |
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5.6 |
Remarks (If any): | |||||||||||||||||||
6.0 |
Closure Approved By Head-QA |
Name |
Signature |
Date |
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Annex-II
Logbook for Planned Deviation Reports
Annex-III
Unplanned Deviation Report Format
| 1.0 |
Initiated By (department): |
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| 1.1 |
Product/Item/Document name/System/facility: |
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| 1.2 |
Batch No./A.R.No./Document No. |
Market: |
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Supplier name, Date of Supply and quantity, In case of Item: |
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| 1.3 |
Batch Size: |
Mfg. Date: |
Expiry Date: |
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| 1.4 |
Deviation related to: |
Environment Control Media Issue Equipment/Instrument TrainingDocumentation Human Error Raw material/Packing material LabellingMaintenance In process Quality Observation SupplyCross contamination In process any Other |
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| 1.5 |
Description of Deviation:Immediate Action Stop Activity Continue Activity Not Applicable |
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Name of Initiator |
Signature |
Date |
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| 1.7 |
Justification for Unplanned deviation/investigation of Unplanned deviation with document reference: |
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Name of Initiator |
Signature |
Date |
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| 1.8
|
Department Head(Comment) |
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Name |
Signature |
Date |
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| 1.9 |
Potential Impact Reviewed by QA: |
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Area Documentation Safety Other Batches Efficiency of maintenance QualificationUtility Process Hold time study Design Lay out CalibrationAnalytical Activity Training Other Product Environmental Condition Regulatory AspectFacility and System Stability Equipment/Instrument Other (if any): |
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| 2.0 |
Root Cause Analysis(Please attach copy and Provide Reference) |
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Concerned Department HeadSign/Date |
Quality AssuranceSign/Date |
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| 3.0
|
Intimation of Unplanned deviation: To be given by QA |
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Department |
Required |
Not Required |
Comments(Acceptable /Not Acceptable) |
Sign/ date |
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QA |
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QC |
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PROD. |
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HR |
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EN |
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WH |
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Any Other |
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| 4.0 |
CAPA Logging Required Not RequiredIf CAPA required reference CAPA NumberIf CAPA Not Required, Justification for same |
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Concerned Department HeadSign/Date |
Head QASign/date |
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| 5.0 |
Review by Plant Head / Director(Comments): |
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Name |
Signature |
Date |
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| 6.0 |
QA Review / Approval |
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6.1 |
Any additional studies required |
Yes / No |
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Stability Studies Additional Quality Testing Others |
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6.2 |
Quality Assurance (comments): |
Sign/date: |
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| 6.3 |
Deviation: |
Approved Rejected |
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| 6.4 |
The Unplanned Deviation is limited to time / No. of Batches: |
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| 6.5 |
Can the Deviation/Change be made permanent through change control? Yes / No |
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| 6.6 |
Review by Head – QA |
Name |
Signature |
Date | |||||||||||||||||||||
| 7.0 |
Implementation of Deviation |
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| 7.1 |
Deviation implemented by (department) |
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7.2 |
Observations (If any): |
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7.3 |
Data Generated (If any): |
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7.4 |
Quality Profile of batches affected(If applicable): |
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| 7.5 |
Implemented ByDepartment Head |
Name |
Signature |
Date | |||||||||||||||||||||
| 8.0 |
QA Review of Implementation & Closure |
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8.1 |
QA comments: |
Sign/date |
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| 8.2 |
All recommendations fulfilled: |
Yes / No |
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8.3 |
If No, Justification: |
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| 8.4 |
Data generation completed: |
Yes / No |
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8.5 |
If No, Justification: |
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8.6 |
Remarks (If any): |
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| 8.7 |
CAPA Closure: |
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Reviewed by QA |
Reviewed by department Head |
Approved Head QA |
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Sign/date |
Sign/date |
Sign/date |
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| 9.0 |
Closure Approved By Head-QA |
Name |
Signature |
Date |
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Annex-IV
Logbook for Unplanned Deviation Reports
Annex-V
Flow Chart for Handling of Planned Deviation
Annex-VI
Flow Chart for Handling of Unplanned Deviation
Annex-VII
Investigation Extension Request Form
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