Deviation control /Non-conformance report (NCR) is the quality management system (QMS) tool is used pharmaceutical industry. This SOP is helpful to understand what the importance of the Deviation control/Non-conformance report (NCR), why Deviation control/Non-conformance report (NCR) is required, what is the procedure to handle deviation control/Non-conformance report (NCR).

This SOP ensures that deviations/Non-conformances from any approved written instructions or procedures are recorded, investigated, and evaluated for their impact on product quality in a manner consistent with cGMP and compliance of the regulatory requirements.

1.0 PURPOSE:

This SOP defines the process of Nonconformance/Deviation control identification, initiation, classification, Root cause investigation, Corrective Action and Preventive Action (CAPA) identification and evaluation, impact assessment and closure of Nonconformance/Deviation control.

2.0 SCOPE:

This SOP is applicable to all employee, personnel, department, role who are involved in or support the designing, developing, receipt, handling, storage, dispensing, processing,  testing,   manufacturing,   packaging,   distributing,   systems,   software operations, facility, validations, qualifications, calibrations, maintenance and documentation of drug product, drug substance and its intermediates.

3.0 RESPONSIBILITIES:

All department who are the part of cGMP is responsible for deviation handling.

3.1 Deviation / Nonconformance viewer/Observer:

3.1.1 Any person (insider or outsider) is responsible to identify the non-conformance/ deviation and report to the respective department/ responsible department.

3.1.2 Provide relevant evidence for that nonconformity observed.

3.2 Initiator (concern department)

3.2.1 Initiating department person inform to QA dept. about non-conformance / deviation after identification and initiate non-conformance / deviation by providing the description of non-conformance / deviation.

3.2.2 Unplanned deviation/non-conformance should report within 24 hours after occurrence and planned deviation/non-conformance should be initiated along with justification.

3.2.3 Initiator fill the related information in “Deviation Control Form/Non-conformance Report”.

3.2.4 Recommend the immediate action and ensure that implementation of recommended immediate action.

3.2.5 Head of the initiator department is responsible for impact assessment and impact area evaluation, identify the root cause and CAPA.

3.2.6 Inform to the other department for the impact analysis.

3.2.7 Ensure all supporting documents, activity identified and performed related to the non-conformance/ deviation.

3.2.8 Identify the necessary action required to identify the root cause and CAPA.

3.2.9 Ensure CAPA should be complete on time.

3.2.10 Check effectiveness and execution of the CAPA.

3.2.11 Whenever required provide training to the required department person.

3.2.12 Ensure non-conformance/ deviation closure, status updation, extension for the approval of non-conformance/ deviation (if required).

3.3 All other departments

3.3.1 Other departments should perform an impact evaluation of the non-conformance/ deviation on related systems and documents and to take necessary action.

3.3.2 Recommend and implement corrective and preventive action (CAPA), whenever required.

3.4 Quality Assurance

3.4.1 Issuance of Non-conformance report /deviation control form.

3.4.2 Assign Non-conformance/deviation number in the Non-conformance/deviation control form and in respective deviation control logbook/register.

3.4.3 Review the detailed description of Non-conformance/deviation, immediate action plan, and justification of user/concern department.

3.4.4 Evaluation of root cause along with initiating department and evaluation of information suggested by other departments

3.4.5 Categorized Non-conformance/deviation and type of Non-conformance /deviation in the change control form.

3.4.6 Review the immediate action plan and evaluation CAPA of Non-conformance/deviation, a methodology for implementation, and impact assessment.

3.4.7 Review of Non-conformance/deviation control after implementation, monitoring the Non-conformance/deviation till closure.

3.4.8 Ensuring for completion of training (if required).

3.4.9 Prepared and maintain the trend of Non-conformance/deviation.

3.4.10 Evaluation of repetitive deviation.

3.4.11 Decisions to accept or reject affected factors due to the Nonconformance /deviation when requested.

3.4.12 Focus on Overdue, Closure trend, CAPA effectiveness trend, identify the reason CAPA effectiveness failure, CAPA extension reason.

3.5 Quality Assurance Head (HOD):

3.5.1 Evaluation, approval, or rejection of Non-conformance/deviation, monitoring the Non-conformance/deviation control closure.

3.5.2 Ensuring that the Non-conformance/deviation control procedure followed as per mentioned CAPA.

3.5.3 Ensure Non-conformances /deviation have an adequate cause investigation and documented properly.

3.5.4 Execution of the CAPA, final investigation report, non-conformances /deviation should be approved by the quality Head. The approver from the Quality is accountable for the conclusions of the Processing Decision Rationale.

3.5.5 Approval/rejection of the extension of deviation.

4.0 DEFINITION:

4.1 Deviation/ Non-conformance:

4.1.1 Deviation/ Non-conformance is any departure from the actual process, system, facility, utility, document, a written procedure, equipment etc. during the manufacturing of the products.

4.1.2 Deviation/ Non-conformance is unexpected event occur while receiving, manufacturing, storage, packing, testing, distributing, documenting the product and no pre-determined procedure is available to resolve and document.

4.1.3 Deviation/ Non-conformance reported intentionally or unintentionally.

4.2 Deviation Control / Non-conformance report:

The procedure in which initiate, action plan, reviews, evaluate, manages, implement, corrective and preventive action (CAPA), approve, reject, and controls the deviation/ Non-conformance. Attached all the relevant documents which are necessary for the deviation control/ non-conformance report.

Examples of Deviation/ Non-conformance –

1. Non calibrated equipment used for manufacturing or testing.
2. Obsolete written procedure followed during manufacturing or testing.
3. Wrong raw material used during manufacturing.

4.3 Planned Deviation:

A planned deviation is a planned departure to any approved written procedure, system, process or specification prior to implementation. It is a temporary approval for the subject which should require impact assessment and approval prior to implementation. Intentionally deviate the written procedure/system/ facility/equipment/material etc. This deviation/ non-conformance reported before occurrence.

Example of planned deviation:

1. Use of different equipment of the same make and principle other than that specified in BMR.
2. Different secondary packaging material used for packing the product.

4.4 Unplanned Deviation:

An unplanned deviation is an unexpected event that results in a departure from the approved written procedure, system, process or specification. It is usually discovered after the occurrence. This deviation is occurred unintentionally/accidentally.

Example of unplanned deviation:

1. Change in the environmental condition (temperature, humidity, pressure differential)
2. Obtained yield not within expected limit.
3. Process parameter steps skip during manufacturing.

4.5 Critical Deviation:

Any departure from any established standard which may have a critical impact on strength, identity, safety, quality, purity, stability, accuracy, physical characteristics and efficacy of the product or cGMP system is a critical deviation.

Example of critical deviation:

1. cross-contamination in the two product or more product.
2. Filter integrity test failure.

4.6 Major Deviation:

Any departure from any established standard which may have a major/moderate to considerable impact upon the strength, identity, safety, quality, purity, stability, accuracy, physical characteristics and efficacy of the product or cGMP system is a major deviation.

Example of the major deviation:

1. Product mix-up
2. Machine /equipment breakdown during process/manufacturing

4.7 Minor Deviation:

Any planned / unplanned departure from any the established standard which may not have any impact upon the strength, identity, safety, quality, purity, stability, accuracy, physical characteristics and efficacy of the product or cGMP system cess is a minor deviation.

Example of minor deviation:

1. Spillage of material during the manufacturing
2. Failure to meet an environmental condition.
3. Minor error in documents which not impact on the data integrity.

4.8 Repetitive Deviation:

The same deviation occurs 3 times in the 6 months review period called repetitive deviation.

4.9 Immediate Action:

Action taken to correct the cause of deviation/ non-conformance.

4.10 Cause:

The reason of occurrence that produces an effect or result.

4.11 Root Cause:

The fundamental/basic reason due to which a Deviation/ Non-conformance occurred

4.12 Probable /Assignable root Cause:

An identifiable or probable reason to which a deviation/ non-conformance can occur.

4.13 Corrective Action:

Action taken to eliminate the cause of a detected nonconformity or defect to prevent a recurrence.

This action taken to rectify the identified cause to prevent a recurrence.

4.14 Preventive Action:

Action taken to eliminate the cause of a potential nonconformity or defect to prevent occurrence.

Action taken to eliminate the identified cause to prevent occurrence.

5.0 PROCEDURE:

5.1 Initiation and logging of deviation / Nonconformance:

5.1.1 The person who observes the deviation/ non-conformance shall inform immediately to concern department person.

5.1.2 Deviation/ non-conformance may be related to the product, drug substance and intermediate, raw material, packing material, document, equipment, instrument, facility, system, approved written instruction, procedure etc.

5.1.3 A planned deviation should be evaluated for impact assessment before being proposed.

5.1.4 More than 3 repetitive planned deviation is not allowed related product formula, process and process parameter. The permanent change should be implemented for that planned deviation.

5.1.5 An unplanned deviation should be reported within one business day after identification, to the Department Head and Quality Assurance.

5.1.6 The User/concern the department should report deviation / non-conformance to the QA department.

5.1.7 Quality Assurance should issue a “Deviation control Form / Non-conformance report”.

5.1.8 Deviation control / Non-conformance report number, Concern Department Name should be entered by Quality Assurance in the Deviation control form/ Non-conformance report (NCR) as well as a logbook or register along with the sign and date.

5.1.9 QA should generate Deviation number / Non-conformance number as below:

5.1.10 Deviation control number should be as DC/YY/ZZZ    or

Non-conformance number should be as NCR/YY/ZZZ   

Where,

DC – Deviation Control   

NCR – Non-conformance Report

YY – Last two digits of the Current. E.g. 20 for year 2020

ZZZ – Serial number starting from 001.

E.g. DC/20/001 or NCR/20/001

5.1.11 After receiving the Deviation control form / Non-conformance report from the QA department.

5.1.12 User department should fill the details in the form as per below

5.1.13 Initiating department person should be fill in the details in the sections provided for Name of person Deviation/NCR reported by/ Observed by.

5.1.14 User department should select an appropriate option where Deviation / Non-conformance is applicable. Below are the options.

Product/ Material/ Process/ Document / System / Facility / Equipment / Other

5.1.15 User department should fill the details related to deviation/ NCR i.e. Batch No. / A.R. No. / Material code No. / Document No., Name of vendor, date of supply and quantity in case of material, Areas of deviation and Description of deviation’.

5.1.16 The description of deviation/NCR should state in details about what, when, where, who, what is expected.

5.1.17 Each NCR / deviation description should address the following points:

5.1.17.1 Describe where did the Non-conformance / deviation occur, who was involved during deviation happened when did the Nonconformance occur

5.1.17.2 Describe what exactly happened in detail

5.1.17.3 Describe the expected condition

5.1.18 If space provided for writing “Description of Deviation” is insufficient, then the same should be written in attachment and attached with the Deviation control Form / Non-conformance for better understanding.

5.2 Immediate Action plan:

5.2.1 Describe the immediate action (e.g. inform to QA/management, corrective activities) and promptly identified potentially affected material/ product/ system/facilities.

5.2.2 Select appropriate immediate action option as below:

Stop activity / continue activity / Not Applicable (depends on the deviation)

5.2.3 In case of an unplanned deviation/ NCR, the concern a person should take immediate action i.e. either ‘stop activity’ or ‘continue activity’. Describe the reason for selection for the above option and justification for the same.

5.2.4 The deviation control form / NCR should be signed by concerned department person along with date and hand over to Concerned Department Head and Quality Assurance for the evaluation.

5.3 Investigation (root cause analysis) and impact assessment:

5.3.1 The concerned department head along with Quality Assurance should review the details filled by the concerned person in the deviation / NCR and if not satisfied with filled details then ask for more details.

5.3.2 The concerned department head and Quality Assurance should evaluate the deviation by discussing with the concerned person and should select the type of deviation i.e. planned/unplanned.

5.3.3 After discussion the concerned department head and Quality Assurance should suggest any additional immediate action, if required.

5.3.4 Stepwise investigation should be done according to the sequential events.

5.3.5 During the investigation, focus on the repetitive deviation/NCR should be checked and accordingly recorded in deviation control form/ NCR.

5.3.6 Based on evaluation on strength, identity, safety, quality, purity, stability, accuracy, physical characteristics and efficacy of the product or cGMP system. Deviation / NCR should be categorized as “Critical, Major and Minor” by QA person.

5.3.7 Describe the justification behind the selection of the category of deviation / non-conformance.

5.3.8 Evaluate the impact on other batches/ Product/ Material/ Process/ Document / System / Facility / Equipment and recorded it.

5.3.9 Following are some examples of critical deviation/Non-conformance:

a) Cross-contamination between manufacturing product.

b) Powder found in the duct (not cover in cleaning procedure) on multi-purpose /non-dedicated equipment (same equipment part of more than one product).

c) Filter integrity test fail in the cleanroom area of an injectable area.

5.3.10 Following are some examples of major deviation/Non-conformance:

a)  Dust/powder found on cleaned accessories of dedicated product.

b)   Use of different equipment of different principles for the manufacturing purpose.

c)  Equipment breakdown during manufacturing

d)  Average weight of product out of limit

e) Expected yield not obtained.

f) Metal detector is not working during the compression of a tablet.

g)  Product rejection sensor (camera) not working during packing

h) Wrong labeling of the product

5.3.11 Following are some examples of minor deviation:

a)  Wrong the secondary packing material used.

b)  Printing error during the labeling (on secondary packaging material)

c)  Old version of SOP not made obsolete before new effective SOP.

d)  Typographical error on batch document.

e)  Person missed entry of non-critical parameter in BMR.

5.3.12 Root cause analysis should be performed by Concerned Department Head and Quality Assurance person as applicable. Attached the details of analysis to the deviation control form/NCR.

5.3.13 In case of critical and major deviations / NCR, a risk assessment should be performed to evaluate the risk on the product strength, identity, patient safety, quality, purity, stability, accuracy, efficacy or cGMP system in consultation with Head of Quality.

5.3.14 In case of minor deviations/NCR (due to human error) 5-why analysis tool should be used. This 5-why analysis report should be attached to the deviation control form/NCR.

5.3.15 During investigation identified that the batch/ batches are affected due to deviation / NCR then the impact of deviation should be assessed on product quality before releasing batch/ batches to the market (examine the stability of the product if required).

5.3.16 Recall all the affected batches/product due to serious deviation/NCR. This decision made by the quality head. e.g Cross-contamination (two different product)

5.3.17 The affected department should be identified by Quality Assurance and intimate about deviation/NCR to other departments to check the impact of deviation on their departmental procedures.

5.3.18 Other departmental persons write their comment on the deviation control form / NCR with sign and date.

5.4 Corrective and preventive action (CAPA) plan:

5.4.1 QA should review the comments of other department head.

5.4.2 Based on impact evaluation of other Department Heads. QA, Concerned Department Head and other Department Heads (only impacted departments) should evaluate need and recommend the areas of corrective and preventive action (CAPA).

5.4.3 If corrective and preventive actions (CAPA) are not required then provide justification for the same and should be recorded in the deviation control form/ NCR.

5.4.4 If corrective and preventive action (CAPA) are required then CAPA should be log in the logbook.

5.4.5 Concerned Department Head and Quality Assurance should recommend/planned the CAPA after logging the deviation/NCR in the CAPA log. The reference CAPA number should be recorded in the deviation control form/ NCR.

5.5 Approval/ Rejection decision on deviation / Nonconformance:

5.5.1 The deviation control form/NCR and recommended CAPA and its impact assessment should be reviewed by Head Quality.

5.5.2 If any more actions are suggested by Head Quality then the same should be updated in the recommended CAPA and impact assessment.

5.5.3 After completion of the all-action and evaluation of deviation / NCR, Head quality should approve or reject the deviation. Enter the comment on approval or rejection of the deviation in deviation control form / NCR with sign and date.

5.5.4 If applicable sent deviation control form / NCR to the customer for approval purpose by Head Quality.

5.5.5 Based on comments received from the customer, Head Quality should record their comments on the deviation control form/ NCR.

5.5.6 All details about deviation sent to Corporate Quality Assurance (CQA) Head for approval (in case CQA dept. available).

5.5.7 If any planned deviation is rejected, it should be closed and canceled. Updated in the remark column of the deviation/NCR log as ‘Cancelled’.

5.6 Closure of deviation/Nonconformance:

5.6.1 All the recommended corrective  and  preventive  actions  related to  deviation  should  be completed prior to closure of the CAPA.

5.6.2 Final deviation should be reviewed for implementation of any additional immediate action as well as all recommended CAPA after that QA should decide for the closure of the deviation.

5.6.3 All type of deviations should be the close within 30 working days from the date of deviation/NCR logging.

5.6.4 If any root cause / investigation / CAPA is not completed within 30 working days in the point just for not closing out. Enter the closure date of Deviation/NCR By QA department with sign and date as per 30 working days.

5.6.5 If any recommended CAPA, action is not completed within the time limit, then such deviation / Nonconformance required “Extension of deviation control/NCR” format for the extension of deviation / Nonconformance.

5.6.6 Fill in the required details of the form by the concerned department and HOD give the justification for the extension of deviation / Nonconformance.

5.6.7 Reason for extension should be reviewed and approved by Head QA after consulting the User Department. The extension request provides an additional 30 days to close the deviation/ Nonconformance.

5.6.8 In case difficult to identify the root cause then identify all probable/assignable root causes and close it after completion of actions.

5.6.9 Close the deviation/NCR after completion of CAPA, probable root cause. Marked as ‘Closed’ in the deviation control / NCR logbook as well as CAPA logbook.

5.7 Trending of deviation / Nonconformance:

5.7.1 Affected batches due to deviation / Nonconformance should be reviewed before the batch release and should be recorded in the batch release checklist/documents.

5.7.2    Deviation control / NCR log should be reviewed every first 6 working days of subsequent month for accuracy, completeness of data, closure of deviations and close out of CAPA by Quality Assurance.

5.7.3 A review of all deviations / NCR should be done during the Annual Product Quality Review (APQR) / Annual Product Review (APR).

5.7.4 Deviation /NCR trend shall be prepared on 6 monthly basis. The heads of Quality or designee must approve completed trend reports. Review all types of deviations / NCR and represent the same graphically.

5.7.5 Based on the review of trend data, Quality Assurance should identify repetitive deviations/Nonconformances. The repetitive deviations should be evaluated and an effective corrective/ preventive action (CAPA) should be initiate.

5.7.6 Information regarding deviations and their CAPA should be reviewed as per for Quality Management Review meeting

5.8 Documentation and record

5.8.1 All record related deviation maintained by QA department (QMS dept.)

5.8.2 All supporting document related deviation/NCR, the investigation report, and corrective and preventive actions (CAPA) should be attached to the deviation control form/NCR.

5.8.3 Whenever a deviation is observed at any stage of manufacturing, packing, or testing, the deviation number should be recorded in the batch record (BMR) or test protocol at a particular stage by Quality Assurance along with sign and date.

6.0   ABBREVIATIONS:

QA- Quality Assurance

HOD – Head of department

SOP – Standard Operating Procedure

NCR – Non conformance report

QMS- Quality Management System

cGMP- current Good Manufacturing Practices

CAPA – Corrective Action and Preventive Action

BMR – Batch Manufacturing Record

No. – Number

7.0 REFERENCES

7.1 ISO 13485: Section 8.5 Improvement   

7.2 21 CFR Part 211.22: Responsibilities of quality control unit  

7.3 21CFR Part 211.100: Written procedure; deviations

7.4 21 CFR Part 820.90: Nonconforming product

7.5 21 CFR Part 820.100: Corrective and preventive action

8.0 HISTORY

Not Applicable

9.0 ANNEXURES

9.1 Deviation Control Form / Non-conformance Report (NCR)

9.2 Extension of Deviation control / Nonconformance Report

 FAQ: