PROCEDURE FOR INVESTIGATION OF OUT OF TREND RESULTS (OOT)
PURPOSE : To lay down a procedure for investigation and evaluation of Out of Trend results, obtained during the release testing and stability study analysis.
SCOPE : This SOP is applicable to for investigation and evaluation of Out of Trend results, obtained during the release testing of key staring material and the release testing/stability study analysis of drug products manufactured
It is also applicable to any unusual trend observed during In-process analysis. In stability study, OOT will not be considered at following time points/study :
At last time point for specific condition e.g. 6-month time point is last time point for accelerated condition.
Test result at expiry
Test results after expiry time point.
Anti-oxidant (because of its high degradation nature).
This SOP is not applicable for engineering batch, demo batch.
This procedure is not applicable to microbial test results, hold time study results, Method Validation and Method Transfer analysis, Cleaning Validation samples during the analysis of laboratory testing. This shall be handled through respective SOP.
CROSS REFERENCE DOCUMENTS
SOP on investigation.
SOP on handling of out of specification.
Preparation and review procedure of Annual product quality Review (APQR)/ Product quality review (PQR).
Handling, Management and investigation of deviation.
Attachment Title
- OOT Investigation form issuance log
- OOT investigation Report
- Flow chart for investigation.
- Handling of OOT Results
DEFINITIONS
An Out of Trend (OOT) result can be defined as: A stability or release result that does not follow the expected trend and is scientifically questionable with respect to the previous result(s) collected during stability studies or observed during the regular batch releases or A stability or release result that predicts out of specification result in future/within shelf life.
OOT Number: The sequential number assigned to any given investigation within the respective
Laboratory Investigation: A documented investigation of an OOT result performed by the laboratory as soon as possible after identifying an OOT result.
Analyst: The person who performs the analysis.
Supervisor: A person with the combination of necessary education, training and experience to approve an initial laboratory investigation.
Hypothesis testing: Testing performed in order to verify a hypothesis which has been put forward as possible cause of an OOT result. Hypothesis testing may consist of repetition of the test procedure or part of the procedure, or of experiments designed specifically with the purpose of identifying an analytical problem. Hypothesis testing can be used in the laboratory investigation or the comprehensive investigation. The results from hypothesis testing can be reported only as part of an investigation report and thus cannot be used for release.
Laboratory Error: Error caused in the laboratory , examples includes but may be not limited to,
Analyst error in connection with performance of the analysis,
Malfunction of the equipment,
Error in the use of standards, calculation of results or transfer of data.
Most probable error: Scientifically justified determination that the results appear to be laboratory error.
Transient equipment malfunction: An isolate instance of faulty operation of the instrument, example of the occurrence or passing of air.
Replacement test/Repeat Test: A test performed on the original sample to replace an OOT result invalidated by a laboratory investigation.
Suspect cause: A hypothesis that cannot be proven, regarding what might have caused the OOT The suspect cause is set forth after an inconclusive laboratory investigation.
Sample (original sample): A sample consists of a defined number of units or a weighed/measured amount of material that is drawn based on rational criteria to ensure that the sample represents the material being sampled.
Resample: A sample drawn at a different time and with a different purpose than the original Re-sampling is permitted in case of sampling or transportation errors or as part of a comprehensive investigation.
Retest: Additional testing performed on the original sample in order to confirm or not confirm an OOT result, where a laboratory error cannot be documented.
Statistical outlier: A test result which by statistical analysis is identified as belonging to a different population than the other test results.
Production: In general, the manufacturing department, but in this procedure production is defined as the department that sends samples to the laboratory for testing. This means that e.g. stability and development departments are included.
Comprehensive Investigation: A documented investigation, which involves relevant organizational units such as QA, QC, production and production development/support. It is initiated as a consequence of an inconclusive laboratory investigation.
Averaging: The validity of averaging depends upon the sample and its purpose. Using averaging can provide more accurate results. For Example:
With HPLC consecutive replicate injections from the same preparation (the determination is considered one test and one results), however, unexpected variation in replicate determinations should trigger investigation and documentation requirements.
Averaging cannot be used in case when testing is intended to measure variability within the product such as powder blend / mixture uniformity or dosage form content uniformity.
Test Plan: A test Plan designed to evaluate and assignable cause hypothesis. The test plan should include a detailed description of the steps to be performed and evaluation criteria for the results. Evaluation criteria may include system suitability requirements, conformation criteria based on the system variability limits, and / or standard repeatability.
RESPONSIBILITY
QC Analyst:
To follow the laid down analytical procedure & protocol and document all the observations during analysis.
To check the data for compliance with the specification before discarding test & standard preparations.
The analyst is responsible to inform QC Executive & above about any Scientifically Questionable results/OOT result.
QC Executive /Astt. Manager/Designee:
To review OOT results objectively and timely.
To issue the OOT form from QA Department.
Initiate and complete the investigation along with analyst
Compilation of raw data and investigation report and ensure that it is documented.
QC Manager/Designee:
To review the investigation report for its correctness and completeness.
To permit Hypothesis testing (if required) and review results.
To authorize retesting (if required) and review results.
To evaluate the cause of OOT whether due to laboratory error.
Communicate the findings to the Head QC and forward the investigation report to QA.
For laboratory error, to implement Corrective and Preventive Actions (CAPA).
QA Executive /Asst. Manager:
Registration of OOT issuance of form for documentation.
To maintain the OOT form Logbook (Attachment-I).
Deriving recommended action and concluding finding of investigations.
To authorize Hypothesis testing and repeat analysis (if required) and review results.
To investigate the sampling error (If required).
Deriving and Initiating CAPA based on type of OOT observed.
Concluding the finding of investigation.
Ensuring completion of investigation with documentation with specified time frames.
Trending of OOT including information of analyst, instrument, test, API/drug product name, cause of failure
QA Manager/Designee:
To review OOT result, QC- Laboratory Investigation Report.
To authorize repeat analysis (if required) and review results.
To check and ensure Training records of Analyst and sampling personnel, MOA, Specifications.
To review the Manufacturing Investigation.
Timely disposition of the batch as concluded through investigation.
To ensure timely implementation of CAPA, recommended in the Investigation Report.
To maintain the OOT form Logbook (Attachment-I) and to archive the filled & completed OOT.
To authorize re-sampling (if required).
Executive/Manager Production:
To initiate manufacturing Investigation
To review BMR/ BPR Stability/ PQR/ Product history
To investigate sampling error (If required).
To compile the documents and to assign actual or probable cause.
PROCEDURE:
OOT results obtained in the laboratory shall investigate in two phase:
Phase-I: Laboratory Investigation
Phase-II: Non-process-related or operator error & Process-related or manufacturing error.
The cause of the OOT result shall be investigated adequately and thoroughly and in timely manner. The results of such an investigation shall be documented. None of the result, including initial aberrant result is omitted from the report.
Identification of OOT results
For existing Products, where a statistical trend is available based on minimum 10 batches data, first evaluate the statistical trend, evaluate UCL and LCL, any result that falls outside of UCL and LCL limit shall be treated as OOT. UCL and LCL ‘ shall be calculated as defined in the SOP on APQR/PQR (Annual Product Quality Review).
For new Drug Products and Drug Substances, where a statistical trend is not available following Criteria 6.4 shall be used to identify the OOT results.
Formulation Release (New Products-whereas 10 batches not manufactured):
Abnormal increases or decreases in pH, LOD/Water shall be investigated under OOT results.
OOT shall be considered in assay, CU, Dissolution and Related Substances results.
Assay: acceptance criteria for assay test as per given table below:
| Specification Limit | Result is OOT if |
| Specification limit as 90.0% to 110% | The result outside 97.0% to 108% shall be considered as OOT. |
This acceptance criteria shall also be applicable for, wherever overages added in product.
Content Uniformity: If any product is passing at CU at L2 Stage, then the obtained result shall be considered as OOT. Further 10 batches trend (Including previous 3) shall be established to derive specification window for OOT. While Product continuously passing at L2 Stage (Like 7 batches out of 10) shall not be considered for OOT. The reference of investigation can be given for same kind of OOT event e.g. all value either on higher side or all values on lower side for content.
Dissolution: If of any product is passing at S2 stage, then the obtained results shall be considered as OOT. Trend shall be established to derive specification window for OOT. While product continuously passing at S2 stage shall not be considered for OOT. The reference of Investigation can be given for same kind of OOT. E.g. All values either on higher side or all values on lower side for drug release. Any individual dissolution result that is scientifically questionable shall be considered as OOT. If product Passing S3 &L3 stage, then reject the batch.
Related Impurities:
Any RI (Known or Unknown)/RS value beyond or 80% of the specification limit shall be considered as OOT and must be investigated to see if the product will meet its full shelf life or the same needs to be reduced. E.g. If the specification limit for RI (known or unknown)/ RS is 0.10%, then any value obtained greater than or equal to 0.08% shall be considered as OOT and must be investigated.
If the specification limit for RI (Known) is 1.0%, then any value obtained greater than or equal to 0.8% shall be considered as OOT and must be investigated.
Any individual RI result, which is scientifically questionable, shall be treated as OOT.
Formulation stability:
Assay: Any assay results which is not within 5% of the previous time point result, shall be consider as OOT. e.g. If the specification limit for assay is 90.0% to 120.0%, and previous time point assay value is 97.0%, then the results obtained as 102.0% or greater and 0% or less shall be consider as OOT.
Dissolution:
If the Difference between any time points from its previous time point is greater than 10%, then it shall be treated as OOT.
Laboratory Investigation
Following to be considered for investigation if results are found Out of Trend:
Results found out of trend.
Any scientifically questionable results obtained due to an error observed by
Any other analysis and analytical data that do not comply with the trend due to any unforeseen reason and leading to discontinuation of analysis.
Any discrepancy observed during data review.
A Laboratory Investigation must be initiated and documented as soon as possible an OOT results is identified. Whenever possible, this should be done before test solutions, reference solutions, control solutions or reagents are discarded. This way, hypothesis regarding laboratory error or instrument malfunctions can be The analyst who had performed the initial analysis shall be designated as Analyst ‘A’.
Preserve all test preparation (including the composite or homogenous source of aliquot) used glass apparatus, original sample, dilutions, powdered sample of crushed tablets printouts etc. related to the analysis until the result are reviewed and verified for correctness. This is vital to facilitate the investigation e.g. transfer crushed powder sample of solid dosage form in double polythene bag and further in closed bottle and preserve. Store the bottle in appropriate storage condition in suitable tray to avoid deterioration.
For any deviation from this SOP e.g. deviation from written specification, sampling plan, test procedure or any other laboratory control mechanism follow procedure specified in SOP for Handling, Management & investigation of deviation.
QC Executive/Asst. Manager shall initiate OOT and shall inform QA department.QA Person shall issue OOT form.
The numbering of OOT is given as per the Following: OOT/NN/Y/XX/ZZ/AAA
Where,
OOT : Denotes out of specification
NN : Denotes Plant Code i.e AA
Y : Denotes API or Formulation (Use A for API & F for Formulation).
XX : Denotes type of sample i.e FP & ST (FP For finished product & ST for stability).
ZZ : Denotes current Year (e.g. 25 for 2025)
AAA : Denotes serial no. of OOT (starts with 001 in each year)
Note: Numbering shall be done separate for both unit.
Investigation by QC Person (Executive/Asst. Manager):
The QC Executive/Asst. Manager shall carry out the investigation and report the finding (Phase-I).
The purpose of the Laboratory Investigations is to identify the root cause of the OOT.
The investigations shall be scientifically defendable and based on the knowledge of the critical parameters of both the sample and the analysis
In the laboratory investigation the possible causes of the OOT results are examined by the analyst and the laboratory supervisor, this shall include initial assessment of laboratory data and evaluation whether failure is due to laboratory error.
The examination should focus on possible causes regarding the actual result and there should be an evaluation of possible causes.
If the laboratory investigation is inconclusive, the laboratory should state a suspect cause in the laboratory, whenever possible.
Following additional checklist items, but not limited to, are to be checked (documented as such) using, as applicable:
Carry out the assessment of the OOT result as soon as the result is reported.
Analyst training verification.
Interview analyst to assess knowledge of correct procedure.
Discuss the test method with the analyst to confirm that the analyst has performed the test procedure correctly.
Examine the test data sheet and accompanying attachments in order to find out whether the results can be attributed to laboratory error.
Arrange for the re-examination of actual test preparations used by the analyst and to the extent possible, the glassware used in the original testing.
Verification of weight balance calibration.
Standardization of Volumetric Solutions used for Analysis.
Quality of Solvents, Reagents and Analytical Solution.
Correctness of Working Standards and/or Reference Standards.
Evaluate the performance of the testing method to ensure that it is performing according to the authorized documents (Specification / MOA / STP/ SOP).
Storage and Handling of Original Sample.
Raw data review.
Calculation and or transcription errors.
Error in dilution/Contamination – of samples, dilution medium, mobile phase etc.
Calibration status and Performance of Instruments used for analysis.
Adequacy of test method with respect to analytical method validation and historical data.
Any previous issue with this product/stages
Any issue with environmental temp./humidity within the area whilst the test was conducted.
Any other parameter pertaining to laboratory error.
Hypothesis Testing:
In case laboratory investigation revealed an obvious cause then regarding what might have happened should be tested to determine the assignable cause for OOT test result after approval and coordination with Quality Assurance Department.
A single/multiple experiments can be initiated based on OOT results observed. The Plan should be prepared by AM/Manager QC or his designee and authorized by Assistant Manager/Manager-QA. The experiment to be performed, sound scientific justification, steps to systematically eliminate possible laboratory error to determine if the failure is due to laboratory error in the testing or product itself.
Hypothesis testing must be documented and may include:
Re-injection of the test solution from original HPLC/GC vial, where an equipment malfunction is suspected.
Re-injection of the test solution after further shaking if homogeneity or dissolution problems are suspected. If possible, re-injection from the original HPLC/GC Vial should be done in the same series.
Further extraction of a dosage form to determine whether it was fully extracted during the original analysis.
Re-weighing or re-pipetting may be used to support a suspect cause but cannot in itself invalidate the original analysis
Use of a different equipment.
Performance by a different analyst.
Prepare and test new stock solution from the original composite sample after approval of QA, if applicable, to determine whether original stock was correctly prepared.
Prepare and test new Composite from the original sample, if applicable, to determine whether original sample prepared was non-homogenous.
Prepare and test a new sample solution from original sample, if applicable, to determine whether the flask used for initial sample solution preparation is suspected to be contaminated.
Prepare a new sample solution after approval of QA if the reagent or chemical used are suspected to be contaminated, deteriorated or wrongly used. Make two aliquot one using existing chemical or reagent and other using new chemical or reagent to identify the probable cause.
“Fresh Preparation of sample shall be restricted for injection only in case if test preparation is not stable” (Ideally fresh preparation should be avoided).
The results from hypothesis is testing can be used only as part of the investigation & thus cannot be used as reportable results for release.
During Phase-I Investigation if required to perform any additional testing apart from hypothesis testing. The Additional testing shall be approved with justification prior to execution.
Conclusive Laboratory Investigation:
After satisfactory review of the above, if cause is assigned, manager/AGM shall allow repeat analysis of same aliquot (if available). In single set/ sample (Original sample drawn) by analyst A (if available) in duplicate set. During repeat analysis usage of same aliquot/ sample (Original sample drawn/ Re sample sample) shall be justified in attachment-II. However, any re-sampling activity shall be approved by QA.The OOT results were caused by an error in calculation or data transfer, valid result can be obtained by correction of the error. For conclusive laboratory investigation QC should evaluate if the laboratory error impacts other batches or products.
Action:
If cause is assignable,
Invalidate the initial OOT results and data shall be stamped as “Invalid Data”.
If the result meet within the trend, release the subject batch.
Identification and implementation of CAPA and implement the action as per CAPA review SOP and CAPA effectiveness SOP.
If the root cause is not assignable to a laboratory error, on the basis of the investigation results, the QC Manager/AGM, in co-ordination with the QA Manager/AGM shall decide on the testing disposition.
They can decide to confirm the OOT. In this case the OOT will be confirmed on the basis of the evaluation of the results obtained.
Further actions shall be made as per Phase-II investigation i.e. full scale comprehensive investigation and all OOT results should be a part of disposition decision.
In case of OOT result reported by external laboratory along with investigation report. The investigation report shall be reviewed by Manager-QC/Quality Head. If Required, Manager-QC/Quality Head shall facilitate a joint investigation at external laboratory.
Reporting of Data:
All results obtained during investigation shall be used for reporting of analytical data.
The use of any replicate injection should be specified in a written, approved test procedure. Acceptances limits for variability should be specified in the method and each individual results obtained from the replicate injection and should be within the required specification.
It is in appropriate to use averaging to hide variability in results, in addition, it is not appropriate the average the initials OOT Results and additional retest or resample results because it would potentially hide variability in the individual results.
Time Frame:
All laboratory investigation shall be completed within 20 working day. Depending on the nature of investigation, if the defined time frame is inadequate, additional time required shall be justified by executive/Assistant Manager and same shall be authorized by manager-QC/Designee.
Documentation and Approval:
Each step in the laboratory investigation must be documented. It should be stated clearly what is an observation and what is hypothesis. The documentation shall include all investigation, findings, evaluation, hypothesis and final justified conclusion which states if the laboratory phase-I OOT investigation is conclusive or inconclusive.
QC Executive/Astt Manager shall compile the report and submit the same to Manager-QC/Quality head. If cause is assignable to laboratory error, Manager-QC/Quality head shall review the report and invalidate the initial OOT results. If immediate assessment does not indicate laboratory error, The QC-Executive in consultation with Manager-QC proceed to initiate Phase-II Investigation.
Manager-QC/Designee shall compile the laboratory Phase-I OOT investigation report and submit the same to QA Department for further evaluation by Astt. Manager/Manager-QA.
Laboratory Phase-I OOT investigation report shall be reviewed and concluded by Head-QA/Designee.
CAPA review shall be made as per requirement. Phase-I OOT report shall be closed after initiating appropriate CAPA in case of Laboratory error, while in case of non-assignable laboratory error, the OOT investigation shall be proceed to Full-Scale Phase-II investigation.
PHASE-II Full-Scale OOT Investigation
The purpose of the comprehensive Investigations is to identify the root cause of the OOT.
The Phase II OOT investigation shall be initiated by Executive/Asst. Manager- QA and manufacturing and shall be reviewed by Manager /GM- Manufacturing as per Attachment-II in close coordination with Manager/AGM of QC and QA Department.
On receipt of the Phase-I OOT investigation report from Quality Assurance Department, the Executive/Assistant Manager-manufacturing reviews the report to know the details of the OOT.
Using the form in Attachment-II, the Executive/Assistant Manufacturing reviews records and documentation of the manufacturing process to determine the equipment, personnel and adherence to the laid down
If necessary, trend analysis of previous batches shall be reviewed for product consistency, ruggedness and prediction to probable cause for OOT
Depending on the nature of investigation and probable cause, personnel from other department such as R&D/ PD Lab/ RA/ CQA may be requested to assist during investigation. Such participation shall be documented in the investigation report.
To ascertain the probable cause, if necessary and justified, analysis of previous batch shall be carried.
The nature and extent of investigation may vary on a case-to-case basis. Detailed investigation shall be carried out by use of tools, but not limited to, 5 Why Analysis, Fishbone diagrams, Brain storming, Failure mode effect analysis etc., to find the root causes.
Review the batch record and other supporting document for the following:
Authorized changes, if any.
Deviations from the standard process.
Quality of the input materials (whether, released on any authorization).
Yields in comparison with regular approved batches.
Time delays, if any.
Change in facility / equipment, if any.
Breakdown of the equipment.
Calibrations of equipment.
Improperly validated process.
Manufacturing operator error.
Improperly functioning equipment / services
Improperly functioning components such as pressure gauge / temperature gauge.
As a part of Phase II Investigation if required, Evaluation of sampling, sample handling and transportation (Including of storage of product prior to sampling) shall be initiated by Executive/Asst. Manager-concerned and shall be reviewed by Manager / AGM of concerned department and QA.
The investigation include:
Review of analytical data for any variation.
Determination of whether there is adequate evidence to establish errors such as contamination or wrong labeling details, inappropriate sampling device or container, etc.
Determination of whether, it could be established unambiguously that the original OOT result was due to Faulty Sampling or Errors in sampling procedure. If yes, proceed as per Attachment-Ill.
Allow re-sampling of the batch.
Re-sampling shall be performed by the same methodology.
Re-sampling shall be authorized by Manager/AGM – QA and documented.
The analysis of resample shall be performed in triplicate by Analyst A, if all the 3 results are passing, then Analyst B (i.e. second analyst) shall carry out analysis of resample in triplicate.
The results are evaluated by Manager / AGM- concerned department & Manager / AGM QA.
If the result complies with the specification, invalidate the initial OOT result and the batch may be released.
If OOT is assigned due to “Sampling Error”, corrective action plan shall be documented and implemented.
Any other actions may be incorporated and apply in certain situations.
Additional Investigations (Including retesting) can be performed to identify potential non-process related errors. The scope of the investigation depends on the issue. This means that the level of investigation and its documentation is anticipated to increase from OOT results at non-critical production steps to OOT results at critical production steps, from OOT results at first purification step to OOT results at last purification step, from OOT results at the API level to OOT results at drug product level.
Re-testing/Additional Testing/Re-sampling
In case it becomes necessary during an OOT investigation, performed additional retesting and protocol should be prepared. This protocol should be approved by QA Department before start of the additional retesting.
Retesting can be part of the Phase-II investigation
Decision to retest should be based on the objective of the testing and sound scientific judgment. It should be initiated by QA after approval of the laboratory investigation if the laboratory has stated a possible (but not proven) cause a laboratory error. Additional investigation in the laboratory can be recommended during the Phase-II investigation.
If no probably root cause is stated in the laboratory Phase-I OOT investigation: Retesting may be initiated later during the Phase II Retesting may be initiated by QC (with QA approval) for unstable samples where retesting shall be initiated as soon as possible after the inconclusive laboratory Phase-I investigation has been completed in order to ensure that the sample material represents the batch.
The number of retest to be performed and the testing endpoint must be determined and documented prior to retesting with a protocol approved by
Retest shall be performed if possible, on multiple days, using different analytical instrument and using different analyst(s).
Generally, all retests approved in the test plan are completed as part of the Phase-II investigation. Each individual test results should be confirmed to its specification limit. However, any failure results observed during the additional re-testing, this also shall report i.e. All valid data should be reported even if more OOT data is generate
Re-sampling
Re-sampling may be part of the Phase-II investigation Re-sampling should be approved by Quality Assurance Department.
Re-sampling can be justified when the Phase-II investigation supports that the original sample is not representative of the batch (e.g. a sampling or transportation error has been identified), or when the original sample is consumed in the analysis.
Attempts to avoid later case should be taken by drawing an original sample large enough to allow retesting.
Re-sampling with the purpose of retesting is only allowed for homogeneous material. The rationale for re-sampling should be documented.
Root Cause:
Report root cause all possible causes listed, investigated and evaluated. To identify the cause, the tool of 5 why analysis may be adopted. By adopting this tool, cause shall be derived in a structured manner. The possible effect of the cause may be evaluated in respect to effect on product quality, compliance with GMP, written documents, validation state etc. and regulatory requirements (what is filed with the authorities).
Document the investigation of possible causes. If possible, attach photos, copies of log books etc.
Corrective Actions:
Once the root cause is identified, immediate corrective action shall be derived. As part of the investigation, mention any further corrective actions to be taken based on identified root cause to isolate the problem, to minimize impact on compliance, product quality and to ensure the safety of consumers.
The Corrective Actions shall describe the details as what has been done to solve the problem.
Preventive Action:
Preventive Action shall identify the actions to prevent reoccurrence of the problem. These may include such things as revision of processes or procedures, creation of new systems, training or re-training if required.
In the column of Preventive Action identify the actions to prevent reoccurrence of the problem. These may include such things as revision of processes or procedures, creation of new systems, training or re-training if required.
Describe in the Preventive Actions the detailed as:
What will be done to prevent the problem from happening again?
In case of a human error, is re-training required?
Should suppliers be contacted?
Should maintenance programs be revised?
Evaluation by QA:
QA evaluates each OOT & shall ensure for the availability of sufficient data, rationale or justification to support the suspected cause as well as challenge the correctness of data.
QA shall also assure that any affected products/items are separated from non-affected Products/items.
QA shall evaluate & give comments as QA Evaluation Part. In case, the OOT Investigation Report needs the evaluation of any other departments such as Regulatory Affairs, Corporate Quality Assurance, Engineering, IOD, as per relevance & customers as applicable QA shall specify the name of the department in Evaluation of relevant department part in the OOT Investigation report to get the evaluation from other relevant departments as specified by QA.
If investigation is likely to extend the time frame, General Manager -Manufacturing shall justify and document the requirement of additional time. The extension of time frame shall be authorized by Head-QA.
Corrective and Preventive Action and Disposition Status of the batch (CIosing of OOT)
The CAPA proposed by GM-Manufacturing shall be reviewed by GM – Quality including conclusion of Investigation report, suggested corrective and Preventive action plan for the batch and overall impact on product quality.
The disposition of the batch or other batches / product and CAPA shall be authorized by General Manager – Quality.
After satisfactory completion of investigation, decision shall be taken by GM Quality for batch disposition and based on that batch shall be approved or rejected.
Time Frame
OOT Investigation must be handled as quickly as possible.
All Phase-II OOT investigation shall be completed within 30 calendar days. Depending on the nature of investigation, if defined time frame is insufficient, extension of time frame shall be justified by head manufacturing and authorized by Head-QA.
Target Completion Date (TCD):
Implementation of Corrective and preventive actions. The document must state the priorities/ Timelines for the completion of corrective & preventive action.
Product disposition
Product disposition should be based on case by case, documented, evaluation of the outcome of the OOT (Phase-I and Phase-II) investigation. All test results, both within trend and OOT, shall be reported and considered in batch release decisions.
Quality Assurance decides the final product disposition. The conclusion must be justified and documented.
OOT results identified and invalidated
In those instances where the OOT investigation has revealed a cause not related to the quality of batch (i.e. laboratory error) and all impacted, results are invalidated, the results should not be used to evaluate the quality of the batch(es).
OOT results identified and confirmed
In those cases, where the investigation indicates an OOT results is caused by a factor affecting the batch quality the results should be used in evaluating the quality of batch. A confirmed OOT results indicates that the batch does not giving the within trend results.
Inconclusive Investigations
In cases where the OOT investigations does not reveal an assignable root cause for the OOT test results and whereas example one OOT results and three within trend results have been found, the original OOT results should be retained in record. Scientific judgment should be used in order to assign the disposition of the test results.
Closure of OOT Investigation Report:
Investigation closure should be performed at the point where conclusions have drawn, corrective preventive actions taken or identified.
Although an investigation may be considered closed, additional, long-term preventive actions may have been identified.
The implementation of CAP A shall be completed as per the target completion date specified in OOT report by the concern department in coordination with The CAPA status shall be monitored periodically & the status of its completion shall be reviewed on target completion date by Quality Assurance department.
Alternate CAPA Target Completion Dates (ATCD):
In case, if the CAPA for the OOT Investigation are not closed/ completed within the said timeline, an interim report including a justification for extension of TCD must be prepared by Concern Department, Any Extension of the TCD must be approved by the AGM-QA/Head Quality.
After implementation of CAPA, the CAPA closure must be reviewed by QA. The CAPA closure shall be attached to the relevant OOT investigation report. Based on the review and compliance of CAPA, QA shall approve the CAPA The CAPA closure approved shall be recorded in CAPA register as per respective site SOP.
Trending & Preventive Action Monitoring:
QA department carries out monitoring & trending of OOT. Trend analysis shall be reviewed by the Heads of Production, Engineering, and Quality. The document shall be approved by Head-Quality. Trending shall be done on every six month basis.
Prepare the trend of the OOT with bar and pie chart for better understanding. Pie charts to be used to identify % of contributory factors causing OOT result i.e. Analyst error, material/product failure, instrumental error or method
Based on evaluation of trending plan of improvement for specific area shall be made and accordingly further actions shall be taken or to plan the further actions.