SOP for Investigation of Out of Specification (OOS) test results.
1.0 Objective :
To lay down the procedure for investigation of Out of Specification (OOS) test result(s) of Finished Products, Stability Samples , Raw Materials, Packing Materials.
2.0 Scope :
This procedure is applicable when analysis results of any test of a Finished Product Sample/ Stability Sample/ Raw Material/Packing Material is not within the limit of pre-defined specification in Quality Control laboratory.
This procedure is applicable when analysis results of any test of a Finished Product Sample/ Stability Sample/ Raw Material/Packing Material is not within the limit of pre-defined specification in Quality Control laboratory.
3.0 Responsibility:
3.1 Head of Quality Control shall be:
3.1.1. Responsible for investigating the laborotary investigations.
3.1.2. Reported the OOS to QA department.
3.1.3. Responsible for taking approval of Quality Assurance.
3.1.2. Reported the OOS to QA department.
3.1.3. Responsible for taking approval of Quality Assurance.
3.2 Quality Assurance shall be:
3.2.1. Responsible for issuance of OOS by request from QC department.
3.2.2. Responsible for investigation of OOS.
3.2.3. Review of OOS reported results.
3.2.4. Initiation of “Failure Investigations” at Manufacturing.
3.2.5. Evaluation of OOS test results & their Action plan.
3.2.1. Responsible for issuance of OOS by request from QC department.
3.2.2. Responsible for investigation of OOS.
3.2.3. Review of OOS reported results.
3.2.4. Initiation of “Failure Investigations” at Manufacturing.
3.2.5. Evaluation of OOS test results & their Action plan.
4.0 Procedure:
4.1 When an out of specification test result is suspected, the analyst shall immediately inform to immediate supervisor / Head/Designee - QC.
4.2 QC Head/Designee immediately inform to QA Head/Designee & request for ‘OOS’ form.
4.3 QA Chemist /Designee immediately issue the OOS form with assigning OOS No. & entry in to the log book.
4.4 The original samples, dilutions glass wares, aliquot of samples shall be preserved immediately once the OOS result is observed & shall be retained till the investigation for OOS is on.
4.5 Investigate all out of specification (OOS) test results (i.e. test results that fall outside the established specification or acceptance criteria) of laboratory testing for Finished Products, Stability Samples, Raw Materials, Packing Materials.
4.6 If the above assessment indicates that laboratory errors were made and an assignable cause related to laboratory error (like incorrect sample preparation, use of improper analytical method or equipment, etc.) is found, the original result is invalidated.
4.7 If OOS test result is due to calculation error, correct the error and report the correct result.
4.8 Head/Designee - QC shall document the assignable cause and suggest suitable corrective action including but not limited to training of analyst and re-calibration of equipment.
4.9 If the OOS test results are due to an identified personal error or transient malfunctioning of instrument, re-analysis of the preserved test preparations or original sample shall be carried by two different analysts in duplicate.
4.10 Head/Designee – QA shall review the results. If the results meet OOS acceptance criteria (Refer Point 4.29), batch shall be released. If the results do not met OOS acceptance criteria, batch shall be rejected.
4.11 If there is no laboratory error identified, perform investigation to find out any sampling error. If sampling error is identified, Head/Designee - QA shall authorize the re-sampling and again follow the procedure from Step No. 4.9. (Use resample instead of original sample).
4.12 If the above assessment indicates that OOS result cannot be attributed to an assignable laboratory error, Head/Designee - QA shall recommend Phase II investigation.
4.13 Head/Designee QC shall complete all details in Annexure and submit to QA for further investigation.
4.14 Head/Designee -QA shall initiate Phase II investigation as per SOP of Failure Investigations.
4.15 Head/Designee QA shall thoroughly review documentation of Batch Manufacturing Record, Batch Packing Record including dispensing of raw materials, adherence to manufacturing steps and critical process parameters, results of in-process tests, yield, equipment or system malfunction, etc. to determine the possible cause of OOS results.
4.16 Head/Designee QA shall review any deviation documented for the batch under investigation.
4.17 Head/Designee QA shall also take into account if the problem had occurred previously and effectiveness of corrective actions taken.
4.18 If the investigation reveals a manufacturing defect, OOS result shall be validated and the batch shall be rejected.
4.19 Head/Designee QA shall evaluate impact of OOS on other batches or product associated with the failure.
4.20 Head/Designee QA shall summarize the aspects of the manufacturing process that may have caused the problem. Head/Designee QA shall document the actual or probable cause and suggest corrective actions including revalidation of the manufacturing process.
4.21 If Phase II investigation does not reveal a manufacturing defect, Head/Designee QA shall recommend Phase III investigation and instruct Head/Designee QC regarding the same as per Annexure-lll.
4.22 Re-testing of a portion of original sample or resample in case of original sample quantity is less or other reason with proper justification, shall be carried out by two qualified analysts in triplicate to determine whether the OOS result has been caused due to instrument malfunction or improper sample handling.
4.23 Head/Designee QC shall check whether the results are within OOS acceptance criteria (Refer Point 4.29). He shall report the results and complete the details as per Annexure – III and submit to Head/Designee QA.
4.24 Head/Designee QA shall recommend suitable corrective action.
4.25 For Raw material OOS test result, Phase – I investigation shall be carried out up to laboratory error. In addition Head/Designee QA shall communicate the results to vendor and request joint analysis if required. If OOS is valid, the initials results shall be considered for the rejection of material.
4.26 For stability sample Phase I investigation shall be performed from to be data station onwards. Finding & investigation shall be carried out with QC.
4.27 All OOS related to microbiology shall be handled as per SOP Handling of Out of Specification Results in Microbiology.
4.28 In case any OOS results are observed in the test of assay and dissolution, this shall be handled as per current specification.
4.1 When an out of specification test result is suspected, the analyst shall immediately inform to immediate supervisor / Head/Designee - QC.
4.2 QC Head/Designee immediately inform to QA Head/Designee & request for ‘OOS’ form.
4.3 QA Chemist /Designee immediately issue the OOS form with assigning OOS No. & entry in to the log book.
4.4 The original samples, dilutions glass wares, aliquot of samples shall be preserved immediately once the OOS result is observed & shall be retained till the investigation for OOS is on.
4.5 Investigate all out of specification (OOS) test results (i.e. test results that fall outside the established specification or acceptance criteria) of laboratory testing for Finished Products, Stability Samples, Raw Materials, Packing Materials.
4.6 If the above assessment indicates that laboratory errors were made and an assignable cause related to laboratory error (like incorrect sample preparation, use of improper analytical method or equipment, etc.) is found, the original result is invalidated.
4.7 If OOS test result is due to calculation error, correct the error and report the correct result.
4.8 Head/Designee - QC shall document the assignable cause and suggest suitable corrective action including but not limited to training of analyst and re-calibration of equipment.
4.9 If the OOS test results are due to an identified personal error or transient malfunctioning of instrument, re-analysis of the preserved test preparations or original sample shall be carried by two different analysts in duplicate.
4.10 Head/Designee – QA shall review the results. If the results meet OOS acceptance criteria (Refer Point 4.29), batch shall be released. If the results do not met OOS acceptance criteria, batch shall be rejected.
4.11 If there is no laboratory error identified, perform investigation to find out any sampling error. If sampling error is identified, Head/Designee - QA shall authorize the re-sampling and again follow the procedure from Step No. 4.9. (Use resample instead of original sample).
4.12 If the above assessment indicates that OOS result cannot be attributed to an assignable laboratory error, Head/Designee - QA shall recommend Phase II investigation.
4.13 Head/Designee QC shall complete all details in Annexure and submit to QA for further investigation.
4.14 Head/Designee -QA shall initiate Phase II investigation as per SOP of Failure Investigations.
4.15 Head/Designee QA shall thoroughly review documentation of Batch Manufacturing Record, Batch Packing Record including dispensing of raw materials, adherence to manufacturing steps and critical process parameters, results of in-process tests, yield, equipment or system malfunction, etc. to determine the possible cause of OOS results.
4.16 Head/Designee QA shall review any deviation documented for the batch under investigation.
4.17 Head/Designee QA shall also take into account if the problem had occurred previously and effectiveness of corrective actions taken.
4.18 If the investigation reveals a manufacturing defect, OOS result shall be validated and the batch shall be rejected.
4.19 Head/Designee QA shall evaluate impact of OOS on other batches or product associated with the failure.
4.20 Head/Designee QA shall summarize the aspects of the manufacturing process that may have caused the problem. Head/Designee QA shall document the actual or probable cause and suggest corrective actions including revalidation of the manufacturing process.
4.21 If Phase II investigation does not reveal a manufacturing defect, Head/Designee QA shall recommend Phase III investigation and instruct Head/Designee QC regarding the same as per Annexure-lll.
4.22 Re-testing of a portion of original sample or resample in case of original sample quantity is less or other reason with proper justification, shall be carried out by two qualified analysts in triplicate to determine whether the OOS result has been caused due to instrument malfunction or improper sample handling.
4.23 Head/Designee QC shall check whether the results are within OOS acceptance criteria (Refer Point 4.29). He shall report the results and complete the details as per Annexure – III and submit to Head/Designee QA.
4.24 Head/Designee QA shall recommend suitable corrective action.
4.25 For Raw material OOS test result, Phase – I investigation shall be carried out up to laboratory error. In addition Head/Designee QA shall communicate the results to vendor and request joint analysis if required. If OOS is valid, the initials results shall be considered for the rejection of material.
4.26 For stability sample Phase I investigation shall be performed from to be data station onwards. Finding & investigation shall be carried out with QC.
4.27 All OOS related to microbiology shall be handled as per SOP Handling of Out of Specification Results in Microbiology.
4.28 In case any OOS results are observed in the test of assay and dissolution, this shall be handled as per current specification.
4.29 OOS Acceptance Criteria:
4.29.1 All reanalysis results should individually pass. (i.e. 4 analysis up to laboratory error and 6 analyses for Phase-III).
4.29.2 Overall RSD should be within limit as per below.
4.29.1 All reanalysis results should individually pass. (i.e. 4 analysis up to laboratory error and 6 analyses for Phase-III).
4.29.2 Overall RSD should be within limit as per below.
Test
|
% RSD
|
Assay
|
NMT 2.0 %
|
Residual solvent(if applicable)
|
NMT 15.0 %
|
Impurity above 0.10 %
|
NMT 10.0 %
|
4.29.3 In case of impurity level below 0.10 %, the values shall individually pass.
4.29.4 In case of other test the values shall individually pass.
4.29.4.1 In case any OOS result is observed in the test of Uniformity of content and Dissolution, this shall be handled as per current edition of USP as given in the chapter <711> for Dissolution and <905> for Uniformity of content.
4.30 Reporting:
4.30.1 QA shall allocate OOS number in the OOS Register and will issue Report number. The OOS Register shall be controlled by QA.
4.30.2 QA shall assign 10 digit control number for OOS is as
OOS / XX/ YY / ZZZ,
Where,
OOS : Out of Specification
XX : FP for Finished Product
SS for Stability Study
RM for Raw Material
PM for Packing Material
YY : Last two digit of current calendar year (05 for 2005, 18 for 2018)
ZZZ : Sequential number starts from 001 to 999.
4.30.3 OOS investigation shall be closed with 30 days of reporting.
4.30.1 QA shall allocate OOS number in the OOS Register and will issue Report number. The OOS Register shall be controlled by QA.
4.30.2 QA shall assign 10 digit control number for OOS is as
OOS / XX/ YY / ZZZ,
Where,
OOS : Out of Specification
XX : FP for Finished Product
SS for Stability Study
RM for Raw Material
PM for Packing Material
YY : Last two digit of current calendar year (05 for 2005, 18 for 2018)
ZZZ : Sequential number starts from 001 to 999.
4.30.3 OOS investigation shall be closed with 30 days of reporting.
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