Training Program on

Handling of Deviation

Introduction : Deviation

Deviation is departure from the established procedure / standard.

Handling of Deviation

Introduction : Deviation

In other words, we can say that Deviation is non-compliance with established

procedure / standard.

Handling of Deviation

Deviation in API: Applicable Guidelines

ICH HARMONISED TRIPARTITE GUIDELINE

GOOD MANUFACTURING PRACTICE GUIDE FOR

ACTIVE PHARMACEUTICAL INGREDIENTS

Handling of Deviation

Scope : Deviation in API

The scope of this presentation is to discuss Handling of deviation in detail i.e.

Identification, investigation, root cause analysis, corrective, preventive action

etc.

Handling of Deviation

Regulatory Prospective:

ICH Q7

t Coral Drugs Pvt Ltd

Section 2.16

Any deviation from established procedures should be

documented and explained. Critical deviations

should be investigated and the investigation and its

conclusions should be documented.

Section 2.3

Quality unit making sure that critical deviations are

investigated and resolved.

Deviation from established procedures are

documented and explained. Critical deviations are

investigated and the investigation and its conclusions

are documented.

Quality unit making sure that critical deviations are

investigated and resolved (Section 3)

Coral Drugs has established and implemented a

Procedure for Handling of Deviation.

SOP# CDPL/SOP/QA/020/12

Handling of Deviation

Regulatory Prospective:

ICH Q7

t Coral Drugs Pvt Ltd

Section 2.5

Product Quality Review

A review of all critical deviations or non

conformances and related investigations;

Section 5.35

Deviations from approved standards of calibration on

critical instruments should be investigated to

determine if these could have had an impact on the

quality of the intermediate (s) or API(s)

manufactured using this equipment since last

successful calibration.

Coral Drugs has established and implemented a

Procedure for Product Quality review. (Section 6.2)

SOP# CDPL/SOP/QA/019/06

Coral Drugs has established and implemented a

Procedure for Handling of Deviation. (Section 6.17)

SOP# CDPL/SOP/QA/020/12

Handling of Deviation

Regulatory Prospective:

ICH Q7

t Coral Drugs Pvt Ltd

Section 6.52

Any deviation noted, in batch production record its

evaluation, investigation conducted (if appropriate)

or reference to that investigation if stored

separately.

Provision's are made in Batch production records for

noting deviation if any. (Refer BPR Remarks sheet)

Handling of Deviation

Regulatory Prospective:

ICH Q7

t Coral Drugs Pvt Ltd

Section 6.53

Written procedures should be established and

followed for investigating critical deviations or the

failure of a batch of intermediate or API to meet

specifications. The investigation should extend to

other batches that may have been associated with

the specific failure or deviation.

Written procedures are established and followed for

investigating critical deviations or the failure of a

batch of intermediate or API to meet specifications.

The investigation are extend to other batches that

may have been associated with the specific failure or

deviation.

Coral Drugs has established and implemented a

Procedure for Handling of Deviation.

SOP# CDPL/SOP/QA/020/12

Handling of Deviation

Regulatory Prospective:

ICH Q7

t Coral Drugs Pvt Ltd

Section 6.72

All deviation, investigation, and OOS reports should

be reviewed as part of the batch record review

before the batch is released.

Coral Drugs has established and implemented a

Procedure for Review of BPR, BCR and analytical

report.

(section 6.5)

SOP# CDPL/SOP/QA/017/06

Handling of Deviation

Regulatory Prospective:

ICH Q7

t Coral Drugs Pvt Ltd

Section 8.14

Deviation in yield associated with critical process

steps should be investigated to determine their

impact or potential impact on the resulting quality of

affected batches.

Section 8.15

Any deviation should be documented and explained.

Any critical deviation should be investigated.

Coral Drugs has established and implemented a

Procedure for Handling of Deviation. (Section 6.5)

SOP# CDPL/SOP/QA/017/12

Handling of Deviation

Regulatory Prospective:

ICH Q7

t Coral Drugs Pvt Ltd

Section 8.20

If time limits are specified in the master production

instruction (see 6.41), these time limits should be

met to ensure the quality of intermediates and APIs.

Deviation should be documented.

Coral Drugs has established the time limit in the all

respective product BPR to meet the quality of the

intermediate and API. (Section 6.5)

SOP# CDPL/SOP/QA/020/12

Handling of Deviation

Regulatory Prospective:

ICH Q7

t Coral Drugs Pvt Ltd

Section 12.22

A Validation report that cross

-reference the

validation protocol should be prepared, summarizing

the results obtained, commenting on any deviations

observed, and drawing the appropriate conclusions,

including recommending changes to correct

deficiencies.

Coral Drugs has established the procedure for cross

reference of the validation report and results are

evaluated after summarized the data incase any

deviation observed. Based on the investigation the

corrective and preventive action are taken to control

the deficiencies.

SOP# CDPL/SOP/QA/005/07

Handling of Deviation

Flow Chart:

Handling of Deviation

Let us Discuss….!!!

Handling of Deviation Procedure in Details….!!!

(SOP#CDPL/SOP/QA/020/12)

Handling of Deviation

• A non-conformance means that something went wrong – a problem has occurred and needs to be

address. Non conformance are addressed with corrective action.

• All identified non-conformance are to be notified to the concerned department head and Quality

Head / Designee.

• All non-conformances are to be recorded on a notification form with complete details as per the

current version of Format CDPL/FR/QA/235

Non-Conformance

Handling of Deviation

Non conformance No shall be allotted by QA department as below:

 Notification of Non conformance Number is NC/XXX/YY

 Where, NC stand for Non conformance

 XXX stands for running serial number

 YY stands for year

For example, 1st Non-Conformance of the year 2017 in the month of January shall be written as NC/001/17.

Non-Conformance Number

Handling of Deviation

• The source or cause of the non-conformance is be identified, allowing for the development of

appropriate and effective action.

• Prompt action is to be documented, together with comment of In-charge

• A Review of the effectiveness of the prompt/corrective action will be undertaken by the Quality

Assurance Department.

• On the successful closure of the notification of non-conformance, the Non-conformance report will

be signed-off by the Quality Manager/Designee with the recommendation for further investigation.

o If yes, follow the deviation procedure

o If No, proceed the activity as per standard procedure.

Non-Conformance

Handling of Deviation

• Deviation are measured differences between observed value and expected normal value for a process

or product condition, or a departure from a documented standard or procedure.

• As per recommendation from NC form, user will initiate deviation form, if needed. (Refer Annexure-I).

• Deviation shall be initiated by the concern department and provide detailed information in deviation

report (Format No. CDPL/FR/QA/015).

• Concern department shall completed the deviation report and submit to QA

• After receipt of report, QA shall assign a number in log book and same shall be mentioned in deviation

report.

Deviation

Handling of Deviation

Deviation number shall be assigned as describe below:

• Deviation number is D/XXX/MM/YY

• Where, D stand for Deviation

• XXX stands for running serial number

• MM stands for month in which the deviation originated and

• YY stands for year

Deviation Number

Handling of Deviation

Based on the deviation details QA will identify the Nature of deviation, it may as follows but not limited to :

• Process parameter

• Quantity mismatch

• Personnel related

• Equipment malfunctioning

• Utility failure

• Material related

• Environmental condition failure

• Others

Nature of Deviation

Handling of Deviation

Examples of Deviation

Activity

Examples

Documents

Wrong

version, Data missing or incorrect data

Procedures

Not followed

Batch records

Step not followed, steps skipped.

Sampling of incoming

material

Damaged or incorrect shipment, incorrect documentation

Batch yield

Established yield or reconciliation not met.

Environmental controls

Parameters exceed

limits.

Quality

Failure error reprocessing,

reinsertion

Data entries

Calculation error, missing of critical reading

Signatures/ Approvals

Inconsistent

Mechanical failures

Mechanical deviation within the unit that results in possible

GMP deviation

Testing

Not performed within time frame

Calibrations

Equipment / instrument out of calibration/ tolerance

Equipment Function/ facility

Equipment/

instrument failure, incorrect equipment/ area

Handling of Deviation

Impact Analysis shall be assessed by concerned QA person.

• During assessment, evaluate the impact on manpower, machine, environment, measurement,

method, materials, ,etc. which is directly affected to the deviation.

• Assess the complete quality parameters.

• Write the correct information in report which can easily assess the potential impact.

Impact Analysis:

Handling of Deviation

Based on nature of deviation and its impact, deviation shall be categorize in two classes as “Major and

Minor”

• Minor : if a deviation is done from any established procedure which may not have any direct impact on

overall quality and safety then the deviation shall be considered as a Minor deviation.

• Major: If a deviation is done from any established procedure which may have any direct impact on overall

quality and safety, then deviation shall be considered as a Major deviation.

Classification of Deviation:

Handling of Deviation

After complete evaluation of the deviation concerned QA person shall discuss with QA Head.

QA Head shall responsible to give a basic recommendation after discussion with management (if required) to

concern department (Deviation originating department).

Recommendation by QA:

Handling of Deviation

• Risk Analysis shall be performed, if deviation is classified as Major.

• Copy of risk assessment document shall be attached with the deviation form.

Risk Analysis:

Handling of Deviation

• During investigation, identify the cause and inquiry on “Who, When, Where, What, Which and How” does

the problem occur.

• Based on question pattern, note / identify the response and refine the problem statement / analyze the

cause.

• Root cause identification will be carried out through the current version of SOP of Root Cause Analysis

(CDPL/SOP/QA/033) and Root Cause Analysis form to be attached with the deviation form.

• Isolate the root cause and record the same in the deviation report.

Root Cause :

Handling of Deviation

• Corrective action shall be taken based upon root cause of deviation to put appropriate checks in place to

ensure the quality and safety of the products and to eliminate the root cause.

• QA shall prepare an action plan and share to the concern department.

• Responsibility shall be allocated for a specific area activity with timelines by mutual discussion with

correlated department.

• Allocated activity shall be performed by concern person in given timelines.

• All activities shall be documented.

• QA shall check the affected area / product covered during corrective action.

Corrective Action (CA):

Handling of Deviation

• Preventive action shall be taken based upon root cause of deviation to prevent the re-occurrence. .

• Preventive action shall be cover training and communication to the concern department on awareness

about the failure of the system, process or deviation from the establish procedure and impact over other

batches, system or relevant document etc.

• Preventive action shall a measure to take to prevent the occurrence in future.

Preventive Action (PA):

Handling of Deviation

• Concern department head shall review all reports and give the comments on above implementation.

• Concern department personnel / head shall give the justification for extension of the deviation, if not

closed with in time frame of 30 days.

• Write existing vs current document no. (if change is made) and attach the supporting documents.

• QA concern person shall verify the recommendation implementation and put the comment in the reports

with note in remarks column.

• If required, plan the re-verification of implemented activity, documents and other related area which have

been covered in concern deviation.

Review, Approval and Closure :

Handling of Deviation

• QA concern person shall review the deviation report, attached supporting report, training records,

implementation copy and other required documents.

• After final review, all documents shall be checked and verified by the QA Head.

• QA Head shall finally approve and close the deviation.

Review, Approval and Closure :

Handling of Deviation