| 5.2.1 |
Frequency/ Follow up:
OOS shall be reported immediately on being aware of OOS results (after being checked, audited and reviewed). OOS investigation for laboratory error should be completed within 3 days from the date of reporting. |
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| 5.2.2 |
1- Laboratory error
2- Process-related or manufacturing error.
When an individual test results does not meet the specifications, it does not indicate that the batch has failed. The cause of the OOS results shall be investigated adequately thoroughly in time. The results of such investigation shall be documented. |
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| 5.2.3 |
OOS reporting and numbering |
| 5.2.3.1 |
When any OOS result is obtained, inform Senior Chemist / Head QC. |
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| 5.2.3.2 |
Log the OOS in “OOS Log” as specified in Annexure, Give OOS No. starting from OOS/YY/NNN and so on.
Where, ‘OOS’ stands for Out of Specification, ‘YY’ stands for last two digits of year and ‘NNN’ stands for serial number of OOS of year YY. For example first OOS noticed in year 2024 shall be numbered as OOS/24/001. |
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| Note:
In case of OOS for tests like description, solubility of product and physical parameters of Packaging Materials like dimensions; same should be informed to production and QA Departments. Depending on requirement by production such may be released based on either deviation or user trial by Production Department. |
| 5.2.4 |
Initial investigation
Following steps shall be taken as the OOS is notified to the senior. |
| 5.2.4.1 |
Check whether the documented method has been followed in every detail. Check against specification /SOP. |
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| 5.2.4.2 |
Where instrument have been used, check whether they have been calibrated and were suitable at the time of use. |
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| 5.2.4.4 |
Retain all test preparations and check the raw data for any clear mistakes such as incorrect preparation, dilution, injection or storage in inappropriate environmental conditions. Also check whether the containers of sample are incorrectly closed and improperly stored. |
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| 5.2.4.5 |
Check whether any deviations had been noted during the time of analysis & whether they were recorded in the work sheet. |
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| 5.2.4.6 |
Record the observation in specified format Annexure and hand over all the data to the Head QC. Do not repeat the testing.
Copy of the relevant work sheet should be attached to OOS investigation form & new work sheet should be issued by Senior Chemist. |
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| 5.2.5 |
Investigation |
| 5.2.5.1 |
Carry out the assessment of the OOS results as soon as the result is reported. |
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| 5.2.5.2 |
Discuss the test method with analyst to confirm that the chemist has performed the test procedure correctly. |
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| 5.2.5.3 |
Examine the work sheet & accompanying attachments in order to find out whether results can be attributed to laboratory error. |
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| 5.2.5.4 |
Confirm the performance of the instruments & ascertain whether the instrument was within the period of validity of calibration at the time of use. |
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| 5.2.5.5 |
Determine that the appropriate reference standards, solvent, reagents and other solutions were used and that they met quality control requirements. |
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| 5.2.5.6 |
Evaluate the performance of the testing method to ensure that it is performing according to the authorized documents (Specification / SOP). |
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| 5.2.5.7 |
All the observations of the review of the entire procedure should be recorded on the checklist for investigation of Out of Specification in Annexure. |
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| 5.2.5.8 |
Inform QA Department about the findings of the investigation by submitting the OOS report in Annexure . |
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| 5.2.5.9 |
The OOS report along with suggested corrective action shall be reviewed and approved by QA Head. |
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| 5.2.6 |
Procedure for Re-examination |
| 5.2.6.1 |
Situations I : (Conclusive Error Retest) |
| 5.2.6.1.1 |
If a clear error has been observed during investigation by QC & QA, arrange for the re-examination of actual test preparation used by the same chemist. If the results obtained are within the specification then repeat the analysis on the aliquot prepared from the same portion of the original sample by the same chemist in duplicate. For the tests other than quantitative tests (e.g. heavy metals, identification etc.) single retesting may be performed. If both these results are also within the specification, average the three passing results and release the batch. |
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| 5.2.6.1.2 |
Investigate the cause of initial lab error. If the results of reanalysis in duplicate are not within the specification follow step 5.2.6.1.8 of situation II If sample quantity is less, reserve sample can be utilized for analysis. Relevant entries should be done. |
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| Note :
The Re-testing should be performed on fresh work sheet.
When a situation is observed where the initial analysis and that of the same sample solution shows Out Of Specification results repeat the analysis by same chemist on the fresh original sample in duplicate. |
| 5.2.6.1.3 |
If the duplicate Re-analysis gives the results within the specification complete reanalysis by a second chemist in triplicate may be initiated for confirming the second duplicate reanalysis performed by the first analyst. Also a suitable passing batch should be simultaneously analysed. |
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| 5.2.6.1.4 |
The results of this passing batch should closely confirm to the initial results (e.g. in case of assay the percentage variation between initial and the reanalysis results should be less than 0.5 %) and ensuring that the results are within the specification. |
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| 5.2.6.1.5 |
If all the results of retesting are within the specification (ensuring that the results of the passing batch is also with the statistical limit of 0.5 %), average it, and substitute the average results for the initial test result (ensure that averaged record it along with the explanation for the initial analysis failure (Clear error Invalidate & disregard the previous results on knowing the probable cause of error. (Record and file the observations with signature). Retain all the data together. |
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| 5.2.6.1.6 |
If results of the reanalysis on the fresh original sample by the same chemist in duplicate found out of specification, retesting on the fresh original sample by the second chemist in triplicate along with the passing batch should be initiated and then proceeds as per the situation II. |
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| 5.2.6.1.7 |
Statistical Acceptance Criteria: The result of the duplicate determination and that of the second chemist (if required) should not exceed the set acceptance criterion. Depending on the type of the test, acceptance criteria should be recommended by QC and QA before starting the testing for Out Of Specification. |
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| 5.2.6.2 |
Situations II |
| 5.2.6.2.1 |
If the results of retesting (triplicate) by the 2nd chemist also are outside the specification, average the results obtained and reject the batch. |
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| 5.2.6.2.2 |
If the results of retesting (triplicates) by the 2nd chemist are individually within the specification and that of the standard comparable to the initial results as mentioned above, re-sampling to be done and joint testing to be performed by the first chemist and the second chemist. This joint testing will be done on fresh and initial sample by both the chemist in duplicate. |
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| 5.2.6.2.3 |
Average result to be reported and the batch to be released. The laboratory error to be investigated. For the test other than quantitative tests (e.g. heavy metals, identification etc.) single retesting may be performed. Invalidate and disregard the previous results on ascertaining the cause of error, document the investigation. |
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| 5.2.6.2.4 |
Statistical Acceptance Criteria: The results of the triplicate determination should not exceed the set acceptance criterion. Depending on the type of the test, acceptance criteria should be recommended by QC and QA before starting the testing for Out Of Specification. |
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| 5.2.6.2.5 |
Whenever the OOS for the process error is confirmed, investigation of the manufacturing activities should be carried out by the QA person. |
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| 5.2.6.2.6 |
When the initial test (Situation I) and (Situation II) on the same sample produces the OOS results, determine whether it is possible that the original sample was non-representative of the whole lot and requires re-sampling. |
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| 5.2.6.2.7 |
Before re-sampling activity, it should be conclusively proved that the original sample was non-representative and also the sampling procedure should be thoroughly reviewed. |
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| 5.2.6.2.8 |
Re-sampling is performed under the authority of Head QA, if the investigation reveals that the integrity of the sample is affected, in such situation a portion of fresh sample from warehouse / manufacturing department is subject to reanalysis. Joint testing shall be done on fresh sample by both the chemist in duplicate. Average result to be reported. For the test other than quantitative tests (e.g. heavy metals, identification etc.) single retesting may be performed. |
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| 5.2.6.2.9 |
If the results of both the chemist are in conformance to the specification individually, the batch may be released (ensure that the average results are within the proven and acceptable range). Investigation into sampling error is to be documented. Retain all the data on retesting and re-sampling together. |
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| 5.2.6.2.10 |
If in a situation where analysis on re-sampling does not meet specification, retesting for OOS ends here and has to go for full-scale investigation of manufacturing activities through QA.
Such re-sampling should be done on 100% basis for the material wherever required. |
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| 5.2.7 |
Corrective Measures / Actions |
| 5.2.7.1 |
Wherever applicable history of the batch shall be tracked down by reviewing the results of the input batches. |
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| 5.2.7.2 |
Training to the 1st chemist to perform the test, if a laboratory error has occurred and the same should be documented. |
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| 5.2.7.3 |
If the testing procedure / sampling procedure needs updation, it shall be done promptly with the due Analytical Method Validation and all concerned shall be informed. |
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| 5.2.7.4 |
When laboratory error has found, QC Head shall take appropriate corrective action to know whether the problem was due to instrument, reagent solution, etc. Refer Annexure . |
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