Oos-out of specification

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT TITLE : HANDLING OUT OF SPECIFICATION 1.0

PURPOSE To describe procedure for Handling Out Of Specification (OOS).

2.0

SCOPE This SOP shall be applicable to all OOS test results of Raw and Packaging Materials, In Process Materials, Finished Products and Stability Samples at PEGASUS, Bhongir.

3.0

RESPONSIBILITIES 3.1

Originating Department shall be responsible for: 3.1.1

Verify the OOS results for accuracy and error.

3.1.2

Report questionable results to QC department.

3.1.3

Initiating the OOS investigation and documentation and reporting to QC department.

3.1.4

Carrying out re-testing as per OOS investigation flowchart, wherever applicable after approval of retest by QC department.

3.1.5

Archiving the OOS investigation reports.

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION

3.2

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 2 of 12

Head - Originating Department Shall be responsible for: 3.2.1

Providing training to the personnel of originating department.

3.2.2

Initiating the actions recommended in investigation report.

3.2.3

Monitor and confirm compliance to actions recommended in the investigation report.

3.2.4 3.3

Head - Quality Assurance shall be responsible for: 3.3.1

4.0

Final disposal of material, if any.

Review and approval of final OOS investigation report.

LIST OF ATTACHMENTS Annexure - 1: Format for OOS Logbook F/PB/QAD/032/24 Annexure - 2: Department code for OOS

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Annexure - 3: Format for record and observation of OOS Results (Phase - I) F/PB/QAD/032/25 Annexure - 4: Format for Checklist for Investigation of OOS F/PB/QAD/032/26 Annexure - 5: Flowchart for OOS Investigation (Phase - I)

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Annexure - 6: Flowchart for OOS Investigation (Phase - II)

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Annexure - 7: Format for Investigation Report for Phase – II Prepared By: Date: SWATHI. KOTLA (Officer QA)

Reviewed By: Date: M. RAJAREDDY (Incharge QC)

F/PB/QAD/032/27 Approved By: Date: A. K. BHATTACHARYA (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION

5.0

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 3 of 12

PROCEDURE 5.1

Frequency: Immediately on being aware of OOS results or within 1 or maximum 2 days after completing analytical test (After being checked, audited and reviewed by immediate supervisor).

5.2

Introduction: OOS results obtained in the laboratory fall into three general categories: 5.2.1

Laboratory error

5.2.2

Non-process-related or operator error

5.2.3

Process-related or manufacturing error.

When an individual test result does not meet the specifications, it need not necessarily indicate that the batch has failed. The cause of the OOS result should be investigated adequately and thoroughly and in time. The results of such an investigation should be documented. Corrective and preventive actions must be taken and should be reviewed during batch release. Phase - I means the Laboratory OOS investigation and Phase - II means the Full scale OOS investigation.

Prepared By: Date: SWATHI. KOTLA (Officer QA)

Reviewed By: Date: M. RAJAREDDY (Incharge QC)

Approved By: Date: A. K. BHATTACHARYA (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION

5.3

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 4 of 12

Action to be taken by Analyst: 5.3.1

When any OOS test result is obtained, log the OOS entry in the OOS log book as per Annexure - 1. The numbering system for OOS shall be as follow: PB / OOS / XXX / YY / NNN PB

indicates Area code allotted by QAD to Pegasus, Bhongir.

OOS

indicates Out Of Specification.

XXX

indicates initiating Department {as per SOP on SOP :- PB/SOP/QAD/001/01}.

YY

indicates two digits year code.

NNN

indicates three digits numerical OOS allocated in an incremental manner starting from 001 from each calendar year.

i.e. PB/OOS/XXX/QCD/13/001 indicates that this is the first OOS raised by the QC department of the Pegasus, Bhongir. 5.3.2

When instruments have been used, check whether they have been calibrated and were suitable at the time of use.

5.3.3

Investigate for the miscalculations, weighing error, transcription errors, incomplete transfer of material, and incorrect settings of instruments parameters.

5.3.4

Retain all test preparations and check the raw data for any clear mistakes such as incorrect preparation, dilution, injection or storage, inappropriate

environmental conditions. Also check Prepared By: Reviewed By: Date: Date: SWATHI. KOTLA M. RAJAREDDY (Officer QA) (Incharge QC)

if the containers of sample are Approved By: Date: A. K. BHATTACHARYA (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 5 of 12

incorrectly closed, improperly sampled and improperly stored and use of expired working/reference standard microbial culture, air bubble in spectrophotometer cell or HPLC system or specified conditions not maintained in dissolution medium. 5.3.5

Check whether any deviations had been noted during the time of Analysis and whether they were recorded in the worksheets.

5.3.6

Record the observations in the Annexure - 3 and hand over to the immediate supervisor with all the original data. Do not repeat the testing.

5.3.7

Protocol / Worksheet should be attached to OOS investigation form and new Protocol / Worksheet is issued by QC department.

5.4

Phase - I (Laboratory OOS Investigation) Investigation by Quality control or immediate supervisor: 5.4.1

Carry out the assessment of the OOS result as soon as the result is reported.

5.4.2

Discuss the test method with the analyst to confirm that the analyst had performed the test procedure correctly.

5.4.3

Examine the test data sheet and accompanying attachments in order to find out whether the results can be attributed to laboratory error.

5.4.4

Arrange for the re-examination of actual test preparations used by the analyst and to the extent possible, the glassware used in the original testing.

Prepared By: Date: SWATHI. KOTLA (Officer QA)

Reviewed By: Date: M. RAJAREDDY (Incharge QC)

Approved By: Date: A. K. BHATTACHARYA (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION 5.4.5

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 6 of 12

Confirm the performance of the instruments and ascertain whether the instrument was within the period of validity of calibration at the time of use.

5.4.6

Determine that appropriate reference standards, solvents, reagents and other solutions were used and that they meet quality control requirements.

5.4.7

Evaluate the performance of the testing method to ensure that it is performing according to the authorized documents (Specification / STP).

5.4.8

Record all the observations of the investigation using checklist for investigation of OOS as per Annexure - 4. The checklist has to be filled by other immediate supervisor.

5.4.9

Suspected error must be investigated by QC personnel and if the error found is genuine then the OOS result must be immediately invalidated and disregarded after appropriate recording and filing.

5.4.10

Analyst and QC personnel both shall review for completeness of entire procedure using the available checklist.

5.5

Action to be taken by immediate supervisor / In-Charge QC Situations I: (Conclusive error retest): 5.5.1

If clear error has occurred, arrange for the retesting of the second aliquot of the same sample solution or aliquot prepared from the same portion of the original sample by the same analyst in triplicate.

5.5.2

If all the three results of retesting are within the specification, average it,

and substitute the average result for the initial test result (ensure that the Prepared By: Reviewed By: Approved By: Date: Date: Date: SWATHI. KOTLA M. RAJAREDDY A. K. BHATTACHARYA (Officer QA) (Incharge QC) (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 7 of 12

averaged results are within the proven and acceptable range) and record it along with an explanation for the initial analysis failure (Genuine lab error reversible error). Invalidate and disregard the previous results on knowing the probable cause of error, (Record and file the observations with signature) Retain all the data together. Statistical acceptance criteria: The percentage RSD of 3 replicate determinations should not exceed the established precision for the test. If immediate supervisor analyst investigation is inconclusive then Situation II: (Inconclusive error retest): 5.5.3 If the result of retesting is outside the specification and there is no clear error, arrange for the prompt retesting in replicates by a 2 nd analyst (with higher experience of testing) using the additional portion of the original sample. Involve Quality Assurance/Production to look at quality trend of other batches for the same test to have an idea whether the results of the earlier batches are within the proven and established range. 5.5.4

If the results of retesting (3 replicates) by the 2nd analyst are individually within the specification, substitute average of these results for the initial test results of the 1st analyst (ensure that the average results are within the proven and acceptable range) and consider them for any decision on batch release, after investigating the cause of the failure of initial results, (Genuine lab error - Reversible error). Invalidate and disregard the previous results on

Prepared By: Date: SWATHI. KOTLA (Officer QA)

Reviewed By: Date: M. RAJAREDDY (Incharge QC)

Approved By: Date: A. K. BHATTACHARYA (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 8 of 12

ascertaining the cause of error (sample integrity being biased); document the investigation with the signature. 5.5.5

If the result of retesting (3 replicates) by the 2 nd analyst are outside the specification, report all the results in the worksheet. It may still be possible that the sample is biased and has laid to the failing results. Retain all the data together.

Statistical acceptance criteria: The percentage RSD of 3 replicate determinations should not exceed the established precision for the test. Situation III: (Investigation of sampling procedure and sample integrity homogeneity and representative portion): 5.5.6

When the initial test and retest on the same sample produces the OOS results, determine whether it is possible that the original Sample was nonrepresentative of the whole lot and requires re-sampling.

5.5.7

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. Re-sampling is not permitted for uniformity of content and dissolution testing failure.

5.5.8

Re-sampling is performed under the authority of Head-QA if the investigation reveals that the integrity of sample is affected; in such situation a portion of fresh sample from warehouse / manufacturing

Prepared By: Date: SWATHI. KOTLA (Officer QA)

Reviewed By: Date: M. RAJAREDDY (Incharge QC)

Approved By: Date: A. K. BHATTACHARYA (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 9 of 12

department is subjected to reanalysis by an experienced analyst in triplicates. If the results (3 replicates) 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. Situation III is not applicable to content uniformity and dissolution test. 5.5.9

If in a situation where re-sampling does not meet specification it is not reversible classification. Retesting for OOS stops here which has to go for full scale investigation into manufacturing or processing through Quality Assurance.

Statistical acceptance criteria: The percentage RSD of 3 replicates determination should not exceed the established precision for the test. 5.5.10 Corrective measures / actions to be taken by QA/QC: 5.5.10.1 Training to the 1st analyst to perform the test, if a laboratory error has occurred and the same should be documented. 5.5.10.2 If the testing procedure/sampling procedure needs updation, it should be done promptly with due analytical method validation and all concerned should be informed. 5.5.11

If the OOS is not sorted at laboratory stage i.e. Phase - I, then Full scale OOS investigation of production process review is required i.e. Phase - II.

Prepared By: Date: SWATHI. KOTLA (Officer QA)

Reviewed By: Date: M. RAJAREDDY (Incharge QC)

Approved By: Date: A. K. BHATTACHARYA (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION

5.6

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 10 of 12

Phase II: Full Scale OOS Investigation: 5.6.1

When the initial assessment does not determine that laboratory error caused the OOS result and testing results appear to be accurate, a full-scale OOS investigation is required. This investigation may consist of a production process review and/or additional laboratory work. The objective of such an investigation should be to identify the root cause of the OOS result and take appropriate corrective and preventative action. A full-scale investigation should include a review of production. Such investigations should be given the highest priority.

5.6.2

Full scale OOS investigation should be carried out when a product does not meet the approved specification or any unusual observations are made during the process of storage, handling, manufacturing or testing of the product and /or initiated by any of the following conditions. 5.6.2.1 OOS investigation (not due to analytical error) 5.6.2.2 Market complaint. 5.6.2.3 Product recall.

5.6.3

Whenever a failure is identified in product or process or system the same should be immediately brought to the notice of Head QA.

5.6.4

The Quality Assurance department under instruction of Head QA shall initiate failure investigation.

5.6.5

Investigation should be extended to all the batches/products, which could have possibly been affected by the failure.

Prepared By: Date: SWATHI. KOTLA (Officer QA)

Reviewed By: Date: M. RAJAREDDY (Incharge QC)

Approved By: Date: A. K. BHATTACHARYA (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION 5.6.6

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 11 of 12

Head QA shall hold the release of the batch during investigation of the subjected batch. Such batch should be quarantine and should not be released for dispatch, till investigation is complete and a decision is made.

5.6.7

If required, Head QA shall decide the cause of action to be taken after consultation with Head-CQA to recall those which might have been affected by the subjected failure.

5.6.8

An investigation report shall be prepared as per given format in Annexure –7

5.6.9

The Flow chart for OOS investigation (Phase - I) given in Annexure - 5 and Flow chart for OOS investigation (Phase - II) given in Annexure - 6 shall be followed in case of an investigation of out of specification / failure.

5.7

Corrective Actions 5.7.1

Based on the outcome of the investigation one or many of the following appropriate activity should be initiated by QA / Production. 5.7.1.1 Change in the process 5.7.1.2 Instrument servicing

5.7.2

Whenever assignable cause is identified and is attributed to improper interpretation of method, the concerned analyst should be provided appropriate training in order to avoid such OOS in the future.

Prepared By: Date: SWATHI. KOTLA (Officer QA)

Reviewed By: Date: M. RAJAREDDY (Incharge QC)

Approved By: Date: A. K. BHATTACHARYA (Manager QA)

Issue Date:-05.07.2014

STANDARD OPERATING PROCEDURE DEPARTMENT: QUALITY ASSURANCE DEPARTMENT

Effective Date 01.08.2014 Review Date 31.07.2016

TITLE : HANDLING OUT OF SPECIFICATION

6.0 Rev. No.

SOP No. PB/SOP/QAD/032/00 Supersedes NEW Page No. 12 of 12

REVISION HISTORY: Effective Date

Prepared By: Date: SWATHI. KOTLA (Officer QA)

Details of revision and Reason of revision

Reviewed By: Date: M. RAJAREDDY (Incharge QC)

Approved By: Date: A. K. BHATTACHARYA (Manager QA)