SOP

 

  1. 1. Objective:

To lay down a procedure for handling out of trend (OOT) results during laboratory

analysis.

  1. Scope:

This procedure is applicable for chemical, physico-chemical and microbiological       results generated during laboratory analysis.

  1. Responsibility:

Quality control and quality assurance

  1. Procedure:

4.1 Procedure for determination of out of trend limit

4.1.1 At least 10 batches data shall be required to set the trend limit.

4.1.2 Critical test parameters identified for product e.g. assay, dissolution etc shall be          considered for out of trend range determination.

4.1.3 Enter the results of batches in excel spread sheet. Calculate the mean and standard    deviation.

4.1.4 Multiply standard deviation with 3 to get the 3 sigma value (3σ).

4.1.5 Calculate maximum trend limit by adding 3 sigma value with the mean and calculate minimum trend limit by subtracting 3 sigma value from the mean value. Refer   below table for example:

Sr. No. Batch Number Assay of Atenolol in %

(Specification limit- 95% to 105%)

1 8001A 98.72
2 8002A 97.94
3 8003A 100.35
4 8004B 99.83
5 8005B 98.89
6 8006B 99.45
7 8007B 98.32
8 8008D 100.78
9 8009D 97.81
10 8010D 99.51
Mean 99.16
Standard deviation (SD) 0.99
3SD 2.97
OOT limit (Lower) 96.19
OOT limit (Upper) 102.13

4.1.6 In case trend limit falls outside the specification then 2 sigma (2σ) approach can be   used with justification. It is also acceptable not to apply OOT for certain test parameter or product if appropriate scientific justification is in place e.g. microbiological assay where specification limits are generally wide and variation in results are generally expected.

4.1.7 Record the trend limit of all products in a format and refer during analysis.

4.2 Reporting and investigation of out of trend results

4.2.1 Analyst shall notify quality control manager in case of out of trend result.

4.2.2 Log the OOT with unique reference number.

4.2.3 Sample and standard solution shall not be discarded before the result and data have been checked.

4.2.4 If obvious laboratory error identified then OOT shall be invalidated with appropriate explanation and repeat analysis shall be performed.

4.2.5 If no obvious laboratory error identified then perform further investigation.

4.2.6 QC shall perform initial laboratory investigation as per issued form. Check below point as part of investigation:

– Correctness of procedure used for analysis

– Examination of raw data including chromatogram, spectrum, weight print outs etc.

– Verification of instrument calibration

– verification of sample, standard solution, solvent, reagent preparation

– Verification of glassware used

4.2.7 Consider for hypothesis analysis if required.

4.2.8 If root cause identified by initial laboratory investigation, carry out repeat analysis   preferably by 2 different chemists.

4.2.9 Initial OOT result shall be replaced by repeat analysis test result. 

4.2.10 In case root cause not identified during initial laboratory investigation, perform     extensive investigation with quality assurance department.

4.2.11 Review the batch manufacturing documents and review the trend of previously     manufactured batches.

4.2.12 If manufacturing process error identified during investigation, then batch disposition shall be based on assessment and scientific justification.

4.2.13 If laboratory and extensive investigation supports initial OOT result; in such case,    OOT shall be considered as confirmed OOT.

4.2.14 Release or rejection decision of batch having confirmed OOT shall be based on      assessment and scientific justification.

4.2.15 Submit filled OOT form and investigation report to quality assurance for review.

4.2.16 Quality assurance personnel shall close the OOT and shall update the log.

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