- To lay down a procedure to investigate an Out of Trend results in the product release.
2.1 Quality Control:
Analyst : Responsible for reporting OOT result and to carry out the investigation.
Supervisor : Responsible for performing Preliminary Laboratory investigation along with the analyst.
Head : To initiate and conclude laboratory investigation and ensure compliance as per SOP.
- 3.1 An Out of Trend results shall be investigated before releasing the batch.
- 3.2 Analyst should check the data for compliance with test specifications before discarding test preparations.
- 3.3 When unexpected results are obtained and no obvious explanation exists, test preparations should be retained, if it is stable.
- 3.4 An assessment of accuracy of the results should be stated immediately and the same shall be informed to the supervisor.
- 3.5 Errors like spillage of a sample solution or the incomplete transfer of a sample composite, the analyst should immediately document what happened by Incident.
- 3.6 Analysts should not be completed the analysis for the sole purpose of seeing what results can be obtained when obvious errors are known.
- 3.7 Compare the current results with one another, in-between the current batch results. Example: Compare the Content uniformity results each other and the difference between the individual results should not be much difference. And investigate if any value is near to the limit.
3.8 Compare the current results with earlier results.
Examples: Compare the current batch results with previous batch results.
- 3.9 THE RESULTS CAN BE DIVIDED INTO THREE TYPES AS BELOW
- 3.9.1 Data as a single result: Assay, pH, average dissolution, and average delivered dose.
- 3.9.2 Data with multiple results: Dissolution testing and delivered dose uniformity of Dosage units.
- 3.9.3 Degradation product and impurities data: Also data reported as a single result; however, they are discussed separately because of the nature of the collection and the reporting of data.
- 3.10 INTERPRETATION OF SINGLE RESULTS
- 3.10.1 When the results are very close to the limit and it is not justified scientifically or statistically, the test shall be repeated to conform the first result; initial results shall be reported, if the repeated results are with in the specification.
- 3.10.2 If the repeated results are out of specification then it shall be investigated as per Out of Specification SOP.
- 3.11 INTERPRETATION OF MULTIPLE RESULTS
- 3.11.1 If the variations like high standard deviation, any result is border line with specification, and All the results are very close to lower or higher limit, the data shall be reviewed and investigate for the reason.
- 3.11.2 Before going to S1 investigate in DR, before going to repeat CU shall be investigate.
- 3.11.3 If the reason is not identified, repeat the analysis to conform the original results.
- 3.11.4 Initial results shall be report if the repeated results are with in the specification. If the repeat results are an out of specification then it shall be investigated as per Out of Specification SOP.
- 3.12 INTERPRETATION OF DEGRADATION PRODUCT AND IMPURITIES DATA
- 3.12.1 If the results of known impurity or total impurity are very close to the limit while releasing the batch, the investigation shall be carried out, the results can be reported if the results can justified scientifically or statistically.
- 3.12.2 If the impurity difference is more than 50% from previous batch result, the same shall be investigated. Sample shall be repeated, if it is not justified scientifically.
- 3.12.3 Initial results shall be report if the repeated results are with in the specification. If the repeat results are out of specification, then it shall be investigated as per Out of Specification SOP.
3.13 LABORATORY INVESTIGATION
- Verify the analyst qualification and discuss the test method with the analyst, conform analyst knowledge and performance of the correct procedure.
- Review the step by step procedure from STP to see if any instruction was omitted or followed incorrectly.
- Review all raw data obtained in the analysis, including prints and actual values, chromatograms for proper data processing to identify anomalous or suspect information.
- Verify that the calculations used to convert raw data values into a final test result are scientifically sound, appropriate and correct.
- Verify if any unauthorized or invalidated changes are made to automated calculation methods.
- Verify the respective calibration records of the instruments used.
- Verify that appropriate Reference / Working standards, solvents, reagents and other solutions were used and they meet the required specifications.
- Verify that special precautions, if applicable, were followed correctly.
- Verify dilution of samples, if applicable, another two dilutions of the sample should be made and retested for comparison.
- Verify the preparation of sample and drug dissolved completely.
- 3.14 OOT NUMBERING SYSTEM
Allot the OOT number as follows, OOT/YYYY/XXXX, Eg: OOT/2021/0001
First 3 digits indicates the OOT (Out Of Trend)
4th digit indicates slash “/” , 5th to 8th digits indicates year (i.e., 2021)
9th digit indicates slash “/”
10th to 13th digits indicates the serial number starts from “0001” for the respective year.
- 4.0 ABBREVIATIONS
4.1 OOS ® Out Of Specification
4.2 QC ® Quality Control Department
6.1 Annexure-1 → Laboratory Investigation report for OOT
6.2 Annexure-2 → OOT Register
LABORATORY INVESTIGATION REPORT FOR OOT
|OOT Number :|
|Product / Material Name|
|Batch No./ AR .No.|
|Limits ( Specification)|
|Specification No/ STP No.|
|Analyst (Sign & Date)|
|S.No||Check list||Observation (Yes / No / NA)|
|1||Analyst trained in the particular test?|
|2||Analytical Method adequate and followed properly (step by step)?|
|3||Evident from the discussion that the analyst has understood Analytical Method and the Operation SOP of the equipment / Instrument?|
|4||Analyst calculated the results using correct potency of the standard?|
|5||Analyst calculated the results correctly as mentioned in Analytical Method?|
|6||Evident that the suitability requirements of the analytical method were all met?|
|7||Any similar occurrence with the analyst earlier?|
|8||Any similar histo ry with the product / material?|
|9||Proper glassware used for analysis?|
|10||Proper volumes of pipettes used for analysis?|
|11||Any obvious evidence of glassware contamination? (Visual)|
|12||Evidence or probability of the glassware was not washed or dried properly?|
|13||Glassware used for analysis properly and legibly labeled?|
|14||Any evidence that the sample was not stored properly?|
|15||Dilutions made in sample / standard preparation as per Analytical Method?|
|16||Environmental conditions (temperature, humidity, light) during analysis appropriate?|
|17||Instrument related problems if any noticed?|
|18||Are there any samples analysed for the same test together with this failing sample?|
|19||If Yes (for the above question), then is there any implication for the results obtained for those samples?|
|20||Reagents / chemicals used of recommended grade and prepared as per the analytical method?|
|21||Correct standard used for analysis?|
|22||Standards, reagents used properly stored?|
|23||Any evidence that the standards, reagents were not properly labeled?|
|24||Standards, reagents used within their expiration dates?|
|25||Evidence that the standards, reagents have degraded?|
|26||Evidence that the reagents, standards or other materials used for test were contaminated?|
|27||Working standards standardized as per the Analytical method?|
|28||Equipment / Instrument used for analysis in calibrated state?|
|29||Any evidence of malfunction of the relevant equipment?|
|30||Preventive Maintenance Programme of the equipment performed as per schedule?|
|31||Appropriate analytical balance used?|
|32||SOP adequate and the equipment operated as per SOP?|
|33||Instrument / equipment meeting the system suitability criteria mentioned in the analytical method?|
|34||Any other Observations / Comments|
|Cause assigned||£ Yes £ No|
|Evaluation and comments:|
|Section In-charge QC (Sign & Date)|
|Retesting required £ Yes £ No|
|Retested results £ Complies £ Does not comply|
|Evaluation and comments:|
|Section In-charge QC (Sign & Date)|
|Conclusion of Laboratory Investigation :|
|QC In-charge (Sign & Date)|
|Final Conclusion :|
|In-charge QA (Sign & Date)|
|S.NO||DATE||OOT NUMBER||PRODUCT||BATCH NO.||A.R.NO||TEST||REMARKS|