SOP ON HANDLING AND INVESTIGATION OF INCIDENT

SOP ON HANDLING AND INVESTIGATION OF INCIDENT

PURPOSE : To define the procedure for incident reporting and investigation.

SCOPE : This guideline is applicable to, All incidents, which can affect the safety, identity, strength, purity and / or quality of the product which can be,

• Facility related.
• Storage related.
• Production related or occurred during processing.
• Raw / Packaging / FP sampling or release related.
• Distribution related.
• Confirmed failures out of repeat analysis and out of specification investigations.
• Any other.

Unplanned deviations from approved procedures e.g. Standard operating procedures, protocol, BMR etc., without prior authorization and documentation.

REFERENCE(S)

World health organization (WHO) TRS 908

Pharmaceutical inspection convention pharmaceutical inspection co-operation    scheme (PIC’s): Guide to good manufacturing practice for medicinal products.

CROSS REFERENCE DOCUMENTS

• Document(s) and Data Control Procedure.
• Change Control Management.
• Corrective and Preventive Action (CAPA).
• Quality Risk Management (QRM.)
• SOP on Investigations.
• Handling, Management and investigation of Deviation.
• Good Document Practice (GDP).

ATTACHMENTS

Incident Log.

Incident Investigation Form.

Cause and Effect (Fish Bone) diagram for incident investigation.

Flow chart for incident reporting and investigation.

DEFINITIONS

Incident:

Any unforeseen event.

Deviations from approved protocols or standard operating procedures without prior authorization and documentation.

Any variance from established specification or requirements stated in Quality System document, which includes but not limited to SOP (Standard Operating Procedure), BMR (Batch Manufacturing Record) and BPR (Batch Packing Record), that would affect the safety, identity, strength, purity and/or quality of the product.

Activity or the operation performed in excess of that defined in a BMR, SOP or other approved documents (BMR may allow adjustment of machine, pH, however a excessive number of adjustments is an incident).

Incident report is specific one time document, when applied as an unplanned deviation to established procedure or specification.

Investigation

General process of information or data gathering, analysis & checking possible causes to find out cause and its impact assessment.

Corrective action

The term “correction” usually refers to the repair, rework or adjustment made to the product as part of the disposition of an existing nonconformity.

A corrective action is an action taken to eliminate the causes of an existing non-conformity, defect or other undesirable situation in order to prevent recurrence.

Preventive action

A preventive action is an action taken to eliminate the cause of a potential non-conformity, defect or other undesirable situation in order to prevent its occurrence.

Note: There can be more than one cause for a potential nonconformity.
Preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence.

Root Cause: The identifiable factor based on objective evidence which have been determined to be responsible for the incident.

Probable Cause: The identifiable factor(s) which is most likely to be responsible for the incidence.

RESPONSIBILITY

QA Department Person:

To prepare SOP for inc

ident Procedure.

Concerned Department person:

To report any incident to a supervisor or department head and / or Quality Assurance (QA) within specified time.

To provide the feedback upon interrogation if required during investigation.

To prepare the incident report and perform investigation within specified time period.

Quality Assurance:

To register the incidence and assign a sequential number to each incident.

To review the incident investigation report.

To monitor the incident reporting and incident investigation as per procedure and timelines defined in the SOP.

To review the justification submitted in incident reported prior to the investigation of the incident with respect to potential product or process impact in order to allow the process           to continue to the next phase of manufacturing, packing or release for distribution, if no         product / process impact is evident.

To review the incident investigation report.

To monitor the recommended corrective action / and implementation through relevant

To close the investigation report.

To perform six monthly review of incidents.

Concerned Department Head:

To assign the responsibility to department representative to perform the investigation.

To ensure that incident is reported to QA within specified time.

To provide the guideline for investigation of the incident.

To review incident investigation report.

To monitor the CAPA.

Quality Assurance Head:

To authorize the extended time for incident investigation and CAPA.

To monitor the activity as per SOP.

To review and approve the investigation report.

To ensure implementation of the defined system.

Plant Head:

To review and approve the investigation report.

To ensure implementation of the defined system.

PROCEDURE:

Reporting of incident:

All incidents must be reported immediately to responsible supervisor or department

Incident shall be initiated in following circumstances

Processing deviation that have affected or potentially could affect a product.

A general system breakdown or failure to follow procedure.

An action limit is exceeded.

A value is outside the processing parameters.

At the discretion of QA department, when there are excessive minor errors and/or recording errors. Errors that are found and corrected by manufacturing; however, are repetitive.

When BMRs are reviewed for product release, QA may issue an incident report based on the information (or lack of required information) recorded in the BMRs/ Records.

A single incident report may be used for more than one lot if the incident was repeated and cause for the incidents is mutually related.

Incident report shall not be issued for minor incidents such as undocumented cross out, write over, or missed steps (When it can be proven that the step had been performed),   but doer/ performer and/or checker failed to document the same.

The QA person shall responsible to fill the “Incidence register”.

The incident register shall be filled as per the following guideline.

Incident No:

Mention incident number as per numbering pattern defined under.

The incident number shall comprise of the department code specific for the
particular department as described in SOP on SOP and year of incident.

The department code shall be suffixed by three digits, year shall be mentioned in two digits and last three digit shall be serial number. For example, the first incident report number for Quality Assurance department for the year 2021 shall be allocated.

The incident details shall be entered in the (hard copy of the) register and the register shall be updated.

The register shall be used to make entries of incident details of more than one department (Department wise sections can be created in the same register to make entries of incidents of different departments).

Date of Reporting:

Mention date on which the incident is reported.

Product/Material/system Name:

Mention name of the product /material / system incident is related to it. Otherwise  mention N/A.

Document No. / B. No. / Equipment No. /A. R. No. /instrument No. :

Mention Document No. / B. No. / Equipment No. /A.R. No/ Instrument No.  if incident is related to it. Otherwise mention not applicable (N/A).

Incident details: Mention detail description of the incident which shall include as defined.

Target date for completion : Mention the target date for completion which shall be NMT 30 days from date of occurrence of the incident.

Responsible Person : Mention the name of the concerned persons / department head to whom the incident investigation report is issued.

Status (Open/close/Cancelled) : Mention the status as open /close, as per time line and investigation closure.

Closure Date: Mention the closure date and sign, as per time line and investigation closure.

CAPA No : Mention the CAPA number issued, if any.

Incident investigation:

Incident investigation shall be done as per investigation action plan decided and investigation details shall be recorded in incident investigation report.

Incident investigation report shall be prepared as per guideline given below.

Incident No.: Mention the incident number.

Date of  Mention the date on which the incident occurred.

Date investigation started: Mention the date on which investigation was started.

Product/Material/Equipment /instrument / system Name:

Mention name of the product /material /Equipment /instrument/ system incident is  related to it. Otherwise mention Not Applicable.

Document No. / B. No. / Equipment No. /A. R. No. /instrument No. :

Mention Document No. / B. No. / Equipment No. /A.R. No./ Instrument No.  if incident is related to it. Otherwise mention not applicable (N/A).

Incident details/description:

Mention detailed description of the incident which shall include, when (stage/time), where (location /area/ room no.) what (parameter out of limit / process not followed / followed wrongly / documented wrongly / any other), by whom (person involved if any), How (incident /malfunction) seen / happened / noticed and Magnitude ( no of units affected and intensity of the impact).Also include impact on product if affected due to incident.

• Following questions can be asked to formulate an incident.
• Identity:
• What is the unit with the malfunction?
• What is the malfunction?
• Location:
• Where is the malfunction seen?
• When was the malfunction seen?
• When has it been last seen since?
• Magnitude.
• What is the extent of the malfunction?
• How many units are affected?
• How much of any one unit is affected?

Target date for investigation completion. :

Mention the target date for investigation completion which shall be NMT 30 days from date of occurrence of the incident.

Revised target date for investigation (if investigation not completed in time). :

In case target date exceeds, revised date shall be assigned by QA head with reason for new target date.

Investigation Team:

QA head shall form a “Team for investigation”, considering nature of incident and department(s) involved in the incident. Name and signature of the persons involved in incident investigation shall be included in report.

Action plan for incident investigation:

QA head shall call a meeting comprising of persons involved with the incident along with concerned department head to discuss the incident and to decide on action plan for investigation. To ensure structured approach while preparing action plan for investigation, fish bone      (cause and effect) diagram shall be used to list out all probable causes. While preparing action plan for incident investigation, following shall be followed/ensured.

• Assemble a team.
• Do not let the expert dominate.
• Do not allow criticism on any idea or probable cause. – Filter later.
• Use a board to record the ideas.
• Rotate around the room, one idea at a time & discuss.
• Limit the number of ideas per person vs. unlimited ideas.
• Leave the notes in place to help others.
• Do not destroy any materials collected related to incident investigation.
• Use structured and not haphazard approach while investigation.
• List out all possibilities & ideas to avoid bias investigation.
• Suggest additional testing / trials if any.
• Define data collection i.e.
• Define observation parameters.
• Define time period to collect data.
• Design data collection format.
• Collect data honestly.

The actions to be taken shall be recorded in incident report by concerned
department head or designee.

Note: Separate, properly identified sheet can be used to record the action plan for incident investigation.

Action plan shall be prepared within 3 days from the date of incident.

Investigation details:

Discussion with concerned person: Summary of interview of the employee who witnessed the incident shall be documented for the exact details of the incident.

Following documents can be reviewed for the investigation of incident based on investigation action plan. Cause and effect diagram shall be referred for investigation.

History (whether such incidents happened in past).

• Manufacturing documents.
• Cleaning/sanitization/sterilization/Depyrogenation records.
• Training documents of concerned persons.
• Qualification /calibration records of equipments / machines.
• Environment monitoring records.
• Trend of process / quality parameters of the product/ equipment/ material used. (comparison of incident batch with other batches).
• Sequential logs of equipments / machines.
• Preventive / breakdown maintenance records of equipments / machines.
• Standard operating procedure.
• Specification / test procedures /sampling procedure.
• Stability data/ data of additional testing/data of trials.
• The investigation report shall also address review of additional testing / trial data as appropriate

Root cause: A clear description of identified root cause of incident shall be recorded based on investigation. If no root cause is identified, it shall be mentioned that assignable root cause not identified and probable cause(s) shall be mentioned. Examples of some of the root causes are given below for guidance purpose.

Causes for production related incidents can be,

• Equipment malfunctioning.
• Working process not defined properly.
• Utility failure.
• Lack of communication.
• Lack of knowledge of working personnel.
• Environment variability (Temperature, Humidity)
• Use of unqualified / uncalibrated machines/equipment’s.

Causes for storage related incidents can be,

• Material lost due to improper storage.
• Not knowing the storage conditions.
• Storage conditions not followed properly.

Causes for material handling /dispensing related incidents can be,

• Spillage during storage.
• Human error in handling.
• Dispensing error.
• Wrong potency based calculation of API

Causes for facility related incidents can be,

• Inadequate facility: Congested, Dirty, cracking, drainage, uncontrolled environment etc.
• Inadequate Equipment: Not meeting range, non-calibrated, not precise etc.
• Inadequate Man-power: Insufficient, un-trained, un-experienced, under-educated for that work etc.

Other causes include following.

• Vendor Change.
• Wrong Specification
• Improper sampling technique
• Improper supervision.

Impact analysis:

Mention the impact of the incident on the quality parameters of the same / other batches, already distributed or ready for distributions. Also evaluate and mention the impact of the incident on different products manufactured on the same / equipment and any other impact the incident may have, depending on the nature of the incident.

Repetitive incident:

If the same incident has occurred more than three times which has impact on product quality or in case of repetitive product failures, QA and Plant head shall decide appropriate actions in consultation with corporate quality assurance head (e.g. discontinuation of further production). To identify the repetitive incident, last one year trend of incident (from the date of the incident) shall be checked. For example if the incident occurred on 15th Jan’ 11, incident history of Jan’10 to Jan’11 shall be checked.

If incident is not repetitive: Release the batch/es and close the incident.

If incident is repetitive: Record the repetitive incident numbers. QA and Plant head shall decide appropriate action plan.

Corrective action taken /Proposed:

Mention the actions taken / proposed to correct machine / system / batch, as applicable.

Preventive actions taken /Proposed:

Mention the preventive actions taken / proposed to correct machine / system / batch, as applicable.

Examples of Corrective action and Preventive action

Incident: Punch breakage while compression of drum no. 5.

Cause identified: Wear and tear on prolonged usage of the punches.

Corrective actions :

Passed the compressed tablets of drum number 5 through metal detector.

Replaced the broken punch set with new punch set.

Destroyed the punch set.

Preventive action: To restrict the use of the tool set upto compression of X million tablets.

Incident: After drying, yield of lubricated granules found approximately X kg less.

Cause identified: Particle flow sensor of FBD was switched off. The operator was not aware of the importance of the sensor.

Corrective actions :

1) Qty of lubricants reduced proportionately before lubrication.

2) Training given to the concerned.

Preventive action: The particle flow sensor shall be put on during the drying operation and shall be ensured by the supervisor and shall be made as a part of FBD checklist.

Information to third party: If required, send investigation report to third party.

Batch disposition: Decision on incident batch/es & other batches disposition whether released or rejected shall be included by QA after approval of the incident report by QA head and Plant head.

Review of investigation Report: Concern department person shall prepared the investigation report and sign/ date. Concerned department head and QA shall review the investigation report and sign  the report.

Remarks of approver: QA head or plant head shall put his remarks, if any, at the time of approval of the incident report. if any.

Approval of investigation report: The concerned department shall forward the incident investigation report to QA and subsequently to QA head and Plant head for review and approval.

Investigation timelines and closing: The concerned department shall complete the report within 30 calendar days of the date of occurrence of the incident. If there is a need of an extension of time, the new time period shall be approved by QA head with justification.

Monitoring of CAPA: Corrective and Preventive actions mentioned in the incident investigation report shall be monitored through relevant SOP at plant e.g. SOP on corrective and preventive action (CAPA). CAPA number shall be recorded in the investigation report where is issued.

Incident Closing: QA shall ensure and evaluate, that all the actions recommended &/or CAPA issued or closed and the related supportive documents attached with the investigation report and close the incident. QA shall mention the incident closure date and sign.

Archival of incident investigation reports: Closed incident investigation reports shall be archived in the QA department. Copy of closed CAPA shall be attached with investigation report wherever issued.

Six monthly review of incidents: Incidents shall be reviewed at least half yearly basis by QA for identification and prevention of repetitive incidents. A review report of the incident shall be prepared and one copy sent to Plant Head along with CAPA, if any.