Deviations handling in Pharmaceuticals

1.0 OBJECTIVE

To lay down a procedure for identification, review, preventing and closure of deviations occurred during the manufacturing.

2.0 SCOPE

This procedure is applicable to all the departments present in the XXX, Place.

3.0 RESPONSIBILITY

3.1 Head-Quality Assurance

3.2 Head-Quality Control

3.3 Head-Production

3.4 Other Heads, if applicable.

4.0 PROCEDURE

4.1 Deviation is an excursion from an expected result or approved procedure.

4.1.1 Examples for potential deviation

4.1.1.1 Production process

4.1.1.1.1 Manufacturing Formula

4.1.1.1.2 Process parameters (e.g. machine parameters)

4.1.1.1.3 Process specifications (e.g. target values in production process or yield limits)

4.1.1.1.4 Testing instructions for in-process

4.1.1.1.5 Controls (e.g. using obsolete versions)

4.1.1.1.6 In-process specifications

4.1.1.1.7 Anomalies in the process

4.1.1.2 Machines, plants, equipment, facilities, and media

4.1.1.2.1 Machine defects

4.1.1.2.2 System failures

4.1.1.2.3 Temperature, humidity, number of particles or pressure differences outside of limits

4.1.1.2.4 Deviations in microbiological monitoring

4.1.1.2.5 Calibration results outside of limits

4.1.1.2.6 Failure to keep calibration or maintenance

4.1.1.2.7 intervals

4.1.1.3 Regulations

4.1.1.3.1 SOP’s

4.1.1.4 Quality control

4.1.1.4.1 Results out of specification (OOS)

4.1.1.4.2 Results out of trend (OOT)

4.1.1.4.3 Results close to specification limit

4.1.1.4.4 Using expired

4.1.1.4.5 reference standards

4.1.1.5 Storage

4.1.1.5.1 Anomalies in pest-control sector

4.1.1.5.2 Exceeding temperature limits

4.1.1.5.3 Anomalies in goods received procedures

4.2 Deviations may be classified into two categories

4.2.1 Planned deviation

4.2.2 Unplanned deviation

4.3 Planned deviation:

4.3.1 Any deviation from established procedure opted deliberately for a temporary period for continual improvement without affecting the quality and safety of drug product is termed as planned deviation. These deviations are pre planned.

4.3.2 No critical or major deviations shall be allowed which has a potential to impact quality of the product, only minor deviation shall be allowed.

4.3.3 Planned deviation shall be raised by the concerned Sr. Executive of the department with “Planned deviation form” as per Annexure-1, by detailing the reasons for the deviation.

4.3.4 The Department Head shall review the proposal for planned deviation, justification given for its potential impact on the product quality and compliance.

4.3.5 After review by concerned head of the department, the proposal shall be forwarded to quality assurance for review and approval.

4.3.6 Head-QA shall review the planned deviation with respect to impact on product quality, necessity / feasibility of the deviation proposed, rationale/justification and compliance to cGMP/regulatory requirements along with the adequacy of the supporting data attached

4.3.7 QA shall approve or rejected planned deviations.

4.3.8 QA shall assign the Number to Planned deviation.

4.3.8.1 IIII/PD/XX/000/00

IIII indicates Company Name

PD represents planned deviation

XX indicates Department

000 indicates serial Number of NC (Starts from 001 to 999)

00 indicates last two digits of the year

4.3.9 Head-QA shall assess the requirement for any additional testing or checks for quality monitoring of the planned deviation and document the same.

4.3.10 If, approved the deviation shall be applicable to defined number of batches or defined number of days and data generated shall be documented.

4.3.11 After QA approval, concerned department shall implement the planned deviation and the observations and data generated shall be documented.

4.3.12 QA shall review the implementation and documented data obtained during the planned deviation to ensure that the recommendations are complying with quality profile of the batch impacted by the deviation.

4.3.13 Closure of the planned deviation shall be the responsibility of the department head and Head QA.

4.3.14 If the planned deviation improves the product quality or process then the deviation can be made permanent change by following change control procedure SOP

4.3.15 QA shall maintain log book for the approved planned deviation as per Annexure-III

4.4 Unplanned deviation:

4.4.1 Any deviation occurred in unplanned manner due to system failure or equipment breakdown or manual error shall be named as unplanned deviation.

4.4.2 Deviations may be categorized according to their severity i.e impact on quality or non-conformance with a GMP standards as follows

4.4.3 Level 3: When the deviation does not affect quality attribute, a critical process parameter, or an equipment or instrument critical for process or control, it would be categorized as minor, and treated as such by the applicable procedure.

4.4.4 Level 2: When the deviation affect quality attribute, a critical process parameter, or an equipment or instrument critical for process or control, of which impact to patients (personnel or environment) is unlikely, the deviation is categorized as major requiring immediate action, investigation, and documented.

4.4.5 Level 1: When the deviation affect quality attribute, a critical process parameter, or an equipment or instrument critical for process or control, of which impact to patients (personnel or environment) is highly probable, including life threating situation, the deviation is categorized as critical requiring immediate action, investigation, and documented.

4.4.5.1 It may arise due to repeated Level 2 deviations

4.5 Deviation reporting procedure consists of three steps

4.5.1 Identification of Non Conformance

4.5.2 Review the Non Conformance

4.5.3 Prevention of Reoccurrence

4.6.1 Identification of Non conformance

4.6.1.1 Identify the deviation based on the 4.1.1

4.6.2 Deviation Reporting:

4.6.2.1 The deviations shall be reported immediately to the Head of the department and Quality assurance department with explicit explanations and the immediate action(s) within 24 hours.

4.6.2.2 The deviation report shall contain information like Deviation number (Assigned by QA), Procedure / product and location at which deviation occurs, and deviation details.

4.6.2.3The deviation details shall also include

4.6.2.3.1 Stage of operation,

4.6.2.3.2 Department name and area,

4.6.2.3.3 Equipment or instrument,

4.6.2.3.4 operator at the time of deviation and

4.6.2.3.5 Nature of deviation.

4.6.2.3.6 Any other relevant information related to deviation

4.6.2.4 Then enter initiator name, Department sign and date by the Deviation initiator.

4.6.2.5 The Head initiator department shall initiate the corrective action required to contain the non-conformity.

4.6.2.6 Then complete the corrective action and record the actions performed.

4.6.2.7 The Quality assurance manager shall evaluate the deviation with respect the impact on quality and propose suitable corrective action based on the nature of deviation.

4.6.2.8 QA-Executive shall classify the deviation and allocate deviation number.

4.6.2.9 Deviation Numbering System format

4.6.2.10 IIII/UD/XX/000/00

IIII indicates Company Name

UD represents Non-conformance or deviation

XX indicates Department

00 indicates serial Number of UD (Starts from 001 to 999)

00 indicates last two digits of the year

4.6.2.11 Enter the details in the Deviation register (Annexure-2)

4.6.2.12 QA shall forward report to Head-QA for authorization.

4.6.2.13 Head-QA shall review the report and can suggest recommendations if necessary.

4.5.4 Investigation Report:

4.5.4.1 Deviation Timing:

4.5.4.1.1 In case of L3 deviation: raise deviation report document immediately upon discovery in the batch record and no need of investigation report.

4.5.4.1.2 In case of L2 and L1 Deviation: investigation report shall be completed within 30 working days from the date of deviation.

4.5.4.2 The Head initiator department together with QA assigns team to investigate the problem.

4.5.4.3 The investigation report shall include but not limited to

4.5.4.3.1What, when, how, where and who

4.5.4.3.2 Investigation details

4.5.4.3.3 Root causes identified

4.5.4.3.4 Quality risk assessment

4.5.4.3.5 Identify other batches potentially affected and

4.5.4.3.6 Conclusion

4.5.4.4 Methods used in the investigation and root cause analysis

4.5.4.4.1 Fishbone diagrams(Ishikawa diagrams)

4.5.4.4.2 Failure modes effects analysis(FEMA)

4.5.4.4.3 Control Charts

4.5.4.4.4 Brainstorming

4.5.4.4.5 Any other relevant method suitable for deviation

4.5.4.5 Data Collection:

4.5.4.5.1 Interview: staff, Customers suppliers

4.5.4.5.2 Review: policies, Procedures and forms

4.5.4.5.3 Record review: training, production equipment and others

4.5.4.6 Whether a deviation shall affect multiple batches, a photocopy of the same shall attach to the Batch manufacturing record.

4.5.4.7 After completion of the investigation as above mentioned identify the root causes and corrective and preventive actions to potentially prevent reoccurrence of similar problem.

4.5.4.8 Raise corrective and preventive actions (CAPA) form as per SOP against deviation and assign target dates, assigned a responsible person & tracked through to closure.

4.5.4.9 Evaluation of the corrective and preventive actions:

4.5.4.9.1 The evaluation for effectiveness should be begin within 30 days and completed not less than 60 days of corrective and preventive action plan.

4.5.4.9.2 Effectiveness evaluation by

4.5.4.9.2.1 Verifying corrective actions were properly implemented

4.5.4.9.2.2 Determine data source for effectiveness evaluation

4.5.4.9.2.3 Determine when to perform and evaluation period

4.5.4.9.2.4 Determine success criteria

4.5.4.9.3 In the event of failed deviation:

4.5.4.9.3.1 Issue new deviation and root cause analysis shall be redone.

4.5.4.9.3.2 There may been multiple root causes that were not initially not discovered.

4.5.4.9.3.3 There may be significant contributing factors that were not initially discovered.

4.5.4.10 QA shall perform post corrective action audit to determine overall effectiveness

4.5.4.11 Quality assurance personnel shall be responsible for to complete the corrective and preventive actions suggested.

4.5.4.12 QA shall close the Deviation by signing the deviation investigation report.