Failure Investigation Procedure and Tools

Standard Operating Procedure (SOP) for Failure Investigation (process failure as well as non-process failure) occurs during manufacturing or processing of drug products.

Failure Investigation

1.0   Objective :

    • To lay down the procedure for failure investigation of any activity to meet its predetermined specification, limits or acceptance criteria.

2.0   Scope :

    • This SOP is applicable to process failure as well as non-process failure (e.g. Operator related) in all departments but not limited to.
      • OOS Investigation (not due to analytical error / non-assignable cause) etc.
      • Failure of Utility system i.e. water system, HVAC failure ,chiller.

3.0   Responsibility :

QA officer/ Executive   :
    • Register the Failure Investigation and assign a sequential number to each failure Investigation
    • Monitor the Failure Investigation reporting and Failure Investigation as per procedure and timelines defined in the SOP.
    • Review the justification submitted in Failure Investigation reported prior to the investigation of the failure 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.
    • Monitor the recommended corrective action / and implementation through relevant SOP.
    • Close the investigation report.
Departments Head  
 / Designee
    • Assign the responsibility to department representative to perform the investigation.
    • Ensure that failure is reported to QA within specified time.
    • Provide the guideline for investigation of the failure and review report and CAPA
Head QA / Designee :
    • Authorize the extended time for failure investigation and CAPA.
    • Monitor the activity as per SOP.
    • Review and approve the investigation report.
    • Ensure implementation of the defined system.

4.0   Procedure – Failure Investigation:

    • Definitions

    • Failure: Failure refers to state or condition of not meeting a desirable or intended
      objective or pre-defined acceptance criteria.
    • Whenever a failure is identified in product or process or system, the particular activity, or Reviewer of the activity operation needs to be brought to the notice of immediate supervisor and QA.
    • QA along with the supervisor of the activity shall carry out a failure investigation as per Annexure-I.
    • Failure Investigation Procedure:

    • The procedure should include the objective for the action that will be taken, the strategy to be followed and the responsibilities assigned to personnel involved in the case.
    • To perform a fact based investigation for determining the root cause during the investigation is essential.
    • The investigation shall be adequate with the significance and risk of the situation shall include:
      • A description of the situation including its impact on product quality, safety, efficacy and purity.
      • A review of all processes and/or system that interact with or may have contributed the cause
      • Based on the information available, identify the probable cause for the non-conformance by using the investigational tools defined in SOP For “Handling of CAPA”.
    • After investigation, summary of the failure and proposed corrective action shall be forwarded to Head-QA for comments.
    • Head-QA / Designee shall initiate CAPA as per SOP in order to avoid the recurrence of the failure of similar or related types.
    • All CAPA documents shall be collected and attached to original failure investigation form for trail and records.

    • Failure observed in manufacturing process which could lead to finished product of non standard quality needs to be documented in the respective batch record.
    • Any out of specification results observed in the laboratory which may have resulted due to failure in the manufacturing process as per the investigation, shall lead to rejection of the batch.
    • For any non process failure observed in a campaign manufacturing, the impact of the same shall be evaluated by QA on the batches produced prior to the reporting of failure.
    • All failure reported shall be serially logged as per the format provide in Annexure- III.
    • Head QA / designee shall quarantine the finished product that might have been affected by the failure.
    • Investigation shall be extended to all the batches / products, which could have possibly been affected by the failure.
    • Head QA / designee shall hold the release of the batch(s) containing rework of the subjected batch(s).

    • Such batches shall be quarantined and shall not be released for sale, till investigation is complete and a decision is made.
    • All corrective actions planned in the investigation report shall be monitored by Quality Assurance for completion of the activities.
    • After completion of corrective actions that are indicated in the report, the same shall be approved by Head – Q.A.
    • A copy of the approved report shall be forwarded to concerned persons.
    • Follow the above steps also for investigation of Out of Trend results (OOT).
    • Numbering system of Failure Investigation Report:
    • Failure investigation report shall be numbered as FR/CC/YY/NNN,
    • where FR stands for Failure Investigation Report,
    • CC stands for department code  ,
    • YY stands for last digit of the calendar year (e.g. ‘21’ for 2021) and
    • NNN stands for number for the failure investigation (e.g. 001, 002….etc.)

6.0   Reference (S)

    • WHO Guideline :  TRS -908: Annexure-4: Good manufacturing for pharmaceutical product: main principles.
    • PIC’s Guideline : Guide to good manufacturing practice for medicinal products  (PE009-09) Part-I.
    • SOP For : Handling and Investigation of Out-of-Specification Results in Microbiology Testing.

5.0   Annexure (S) – Failure Investigation :

Annexure I :  Investigation Report

Failure Investigation Report
Failure Investigation Report Number
Product(s) Name  / SOP Title / System Name / Other (if any)
B. No. / SOP No. / Other (if any)
Description of Failure :
Investigation Details :  (Attached addition sheet if required)
Corrective Action :
Preventive Action
Department Name Designation Sign Date
Quality Assurance        
Head QA        

Annexure II :  Batch Failure investigation Checklist

Batch Failure investigation Checklist
Failure Investigation Report Number Date
Description of Failure
Affected Product(s) & Batch Number(s)
Probably affected Product(s) / Batch (s)
Reference of similar Instance(If any)
Immediate action / decision for the affected product(s) / batch(s), till complete investigation
Initiated By sign & Date : Reviewed By sign & Date :

Investigation Check listInvestigation to be carried out on following criteria but not limited to :

A.      Used Raw/Intermediate Material Validity

B.      Review of Batch Manufacturing Record

C.      Process Deviations

D.      Other Criteria for Failure

E.      Summary of the Data /Results

F.      Conclusion

G.   Suggested Corrective Actions

Used Raw Material Validity

Check points Status
Are all raw material received from approved vendor?

Analytical report of Raw Material

Check the accountability/inventory  of Raw Material
Is Raw Material stored in proper storage condition?
  • Source of RM used: ……………………………………………………
  • A R No. of RM used ……………………………………………………
  • Potency calculation  ……………………………………………………
  • Findings: -…………………………………………………………………

Review of Batch Manufacturing Record (BMR)

Checkpoints Status
Check the issued BMR is of existing validated Process?
Master Receipt
Are there any major deviation noticed during process?
Check the calculation and consumption of  Intermediate / RM
Is counter check done by production during material addition?
All the steps followed as per instructions in the BMR?
Temperature and Humidity of process area
% Yield of intermediate stages
Testing and Release
In process sampling and quality control
Equipment cleaning and usage log books (s)
Finished product sampling and quality control
Temperature and Humidity of primary packing area.
Is the final yield within limits?
 Non–viable particle count in aseptic areas
 Viable count in aseptic areas or environment monitoring result and trend

      Additional sheets shall be attached, wherever required.

Checkpoints Status
Personal monitoring results
Visual inspection results /rejects
Filter integrity records
Pressure differential monitoring records
Washing (Closure /container ) Process records
Water system control

Findings: …………………………………………………………………………………………

Review of actual work habits vis-à-vis compliance of the operation SOPs.
Review of Observation of Operation (s) Deviation Observed Remarks / Comments / Results
Other Criteria for Failure:
Summary of the Data / Results :
Suggested Corrective Actions
Final Review comments by Head QA:
Verification of the suggested Corrective Action Verified by QA(Sign/Date)

Annexure III : Investigation Log  





report No.

Department Name of Product / SOP / System /Others B. No. / SOP No./ Others Description of Failure Suggestive CAPA Closing Date Sign/ Date  


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