HANDLING OF OUT OF SPECIFICATION RESULTS

1.0 OBJECTIVE
To lay down a procedure for handling of In-Process Samples and Finished Products out-of-specifications test results [except Microbiological Analysis]
2.0 SCOPE
This SOP is applicable to Quality Assurance Department.
3.0 RESPONSIBILITY
Head of Respective Departments
4.0 ACCOUNTABILITY
Manager - QC
5.0 PROCEDURE
5.1 Any out-of-specification test result shall be investigated and documented. The investigation report shall include,
5.1.1 Errors in sampling, handling and storage of sample.
5.1.2 Error in Analysis.
5.1.3 Error in manufacturing (process related, non-process related and operator related).
5.2 In case investigation reveals out of specification result is due to manufacturing error, the batch shall be rejected.
5.3 In case investigation reveals that sampling is one of the reason for out of specification result, the repeat analysis shall be done on re-sample.
5.4 In case investigation reveals that out-of-specification results is solely due to analytical error, the repeat analysis shall be performed on same sample.
5.5 If repeat analysis result is found within specification, following step 5.3 and 5.4 then the sample shall be approved. If the analysis result is found out of specification, the sample shall be rejected.
5.6 When investigation does not reveal any abnormalities, due to assignable cause, then repeat analysis shall be performed (except uniformity of Dosage Units and Dissolution Test) by following procedure :
a. Same sample shall be re-analyzed. (i.e., Analysis shall be done on a second aliquot from the same portion of sample that was the source of the first aliquot or Analysis shall be done on portion of the same larger sample previously collected for Laboratory purpose.)
b. Analysis shall be done in triplicate by two analysts . Out of two analysts one may be the original analyst.
5.7 The original out-of-specification test result shall be ignored if,
a. Each test result is within specification.
b. Each set of triplicate results show RSD less than 3%.
c. Difference between average value by the two analysts is less than 3%.
5.8 The original out-of-specification test result shall not be averaged along with repeat analysis results.
5.9 The average of average values reported by individual analyst shall be reported on Analytical Report.
5.10 If repeat analysis results do not meet the specification the batch shall be rejected.
5.11 Annexure - II shall be used for documentation of investigation.
5.12 USP procedure shall be followed for out-of-specification test results for uniformity of dosage units testing if the cause is non-assignable.
5.13 USP procedure shall be followed for out-of-specification test results for Dissolution testing of 6 units if the cause is non-assignable.
5.14 In case of rejection of samples, thorough investigation shall be done involving Production Manager, Product Development Manager and General Manager - Quality Assurance / Senior Group Leader and the same shall be documented.
5.15 The investigation shall be completed within 30 days after QC rejection of the sample. Investigation report shall outline the corrective actions necessary to save batch to prevent similar reoccurrence.
5.16 The investigation shall be extended to other batches and products possibly affected due to process related error.
5.17 The investigation shall also be extended to other batches and products possibly affected due to operator error or malfunctioning of equipment.