by - 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 etc.
2. SCOPE
This SOP is applicable when analysis results of any test of Finished Products, Stability Samples, Raw Materials & Packing Materials etc. is not within the limit of pre-defined specification in Quality Control laboratory manufacturing facility.
3. RESPONSIBILITY
Analyst / Section Head / RM/ FP/ In-charge of Quality Control.
4.0 ACCOUNTABILITY
Head- Quality Assurance
5.0 PROCEDURE
5.1 Whenever a raw material / product is found to be out of specification, the analyst performing the analysis shall inform the matter immediately to the Head of Quality Control. The Quality Control Head will carry out the investigation, as per the guideline given below. Evaluate all the following point at one time, record the observation.
5.1.1 Evaluation of procedure.
5.1.2 Calculations.
5.1.3 Training.
5.1.4 Reagents and volumetric solutions.
5.1.5 Working standards / reference standards.
5.1.6 Calibration status of instrument used.
5.1.7 Sampling procedure and sample storage.
5.1.8 Correctness of method of analysis specified in the specification.
5.2.1 Evaluation of Procedure:
Check by discussing with the analyst and by checking data recorded on the protocol. Whether the procedure followed for analysis is exactly as per the lay down procedure in the specification or official monograph with respect to weight of sample taken, dilutions, use of proper glassware, steps followed etc. If not necessary corrective actions shall be taken.
5.2.2 Calculations:
Check the calculations including mathematical formulae used considering the weights and Dilutions. If needed recalculate the result.
5.2.3 Training:
Confirms whether the analyst, who has carried out the testing, is trained for that particular type of analysis in question. Retest the sample with another trained person if first analyst is not proper trained.
5.2.4 Reagent & volumetric solutions:
5.2.4.1 Check the reagents and volumetric solutions for their validity and appearance.
5.2.4.2 Check whether the reagents used are of required concentration and grade.
5.2.4.3 Prepare fresh reagent / volumetric solution if the solution is not as per the requirement and carry out the retesting.
5.2.5 Working standards / Reference standards:
Check and ensured that the standards used for their validity and storage conditions. Reconfirm the Assay, LOD / water content value if required.
5.2.6 Calibration Status:
Check the instrument / apparatus for calibration calibration status. If needed recalibrate the instrument.
5.2.7 Sampling procedure and Sample storage:
5.2.7.1 Confirm whether sampling is done as per lay down standard procedure or not.
5.2.7.2 Check whether the sample under subject is stored properly or not by observing the sample physically for deterioration by discoloration, absorption of moisture and losing of moisture.
5.2.7.3 Review and check the sampling accessories w.r.t. Cleaning procedure and cleanliness.
5.2.7.4 If sample found damaged or not collected as per the lay down procedure then plan for re-sampling and carry out the analysis on the resumed material.
5.2.8 Correctness of method of analysis specified in the specification:
Method of analysis / supplement to the pharmacopoeia.
Check and review for correctness method of analysis specified in the specification of out of Specification as per latest addendum/ supplements to the pharmacopoeia.
5.3 Evaluate each and every step by Head of Quality Control mentioned in 4.2.1 to 4.2.8 as per the checklist in the evaluation report to draw conclusions from the same. If the sample in question passes after taking the corrective steps mentioned above, depending on the corrective action taken, the Quality Control Head will decide for reanalysis of the sample under subject by another trained person.
5.4 If the sample fails even on repetition, the Quality Control Head will decide followings.
5.5 Reanalysis of the sample under subject by another trained person along with a passed sample.
5.6 Re-sampling and retesting. If the sample passes then review the following points shall be reviewed for determining the reason for earlier failure.
5.6.1 Sampling procedure.
5.6.2 Manufacturing procedure.
5.6.3 Reason for sample-to-sample variation.
5.6.4 Review of point. Based on the review sample under subject and Released the RM/ Intermediate/ Finished Product.
Note: The earlier analyst shall be retrained for that particular analysis. Review of the earlier batches analyzed by him shall be taken.
5.7 If the sample and passed sample fail, reinvestigate the matter by head of Quality Control, find out the actual cause of the failure & reanalysis shall be repeated twice by different persons before release or rejection of the sample.
5.8 If the sample fails and passed sample passes, Reject the Raw material by affixing ‘REJECTED’ labels on all the containers.
5.9 Quarantine the Intermediates / Finished products by affixing ‘QUARANTINE’ label on all the containers.
5.10 In case of Raw material the rejected containers shall be transferred to the Rejected area in Raw material stores.
5.11 In case of Intermediate Product / Finished Product the Production department Head and General Manager shall be informed and further investigation carried out by doing review of the Batch Manufacturing Record with respect to following points and record the observation and investigation report in as per the guideline.
5.11.1 Weights of ingredients added and calculation sheet.
5.11.2 Correctness of measuring device.
5.11.3 Correct sequence of addition of materials.
5.11.4 Correct maintenance of temperature/pressure/stirring speeds/stirring time etc.
5.11.5 Correctness of in-process checks.
5.11.6 Any interruption occurred during batch manufacturing.
5.11.7 Discussion with concerned Officers and Workmen for any deviation occurred during Batch manufacturing, filling and packing.
5.11.8 Environmental conditions during manufacturing and storage.
5.11.9 Stock checking of Raw materials.
5.11.10 Evaluation of raw materials on the basis of Trend analysis.
5.11.11 previous history of product for similar failure.
5.12 The investigation report along with the sample shall be forwarded to Formulation Development through Quality Assurance. Action taken to avoid reoccurrence shall also be informed to Corporate Office.
5.13 From Formulations Development shall study the investigation report and the sample and suggest the necessary reworking procedure through Quality Assurance. The reworking of batch shall be carried out.
5.14 If corporate office rejects the batch it shall be destroyed.
5.15 Documentation:
All documents related to the lot or batch in question shall be compiled by Quality Control / Quality Assurance / Production Department and reports of all such investigations shall be filed separately and maintained by Designee/In-charge QA. QA shall maintain the OOS log.
5.15.1 After completion of investigation, if a raw material is rejected, the same shall be intimated to Purchase Department through Material Received Report.
5.15.2 OOS No. shall be given in a sequential manner as given below.
5.15.3 For raw materials, intermediates and APIs (both sterile and non-sterile) syntax for OOS.
OOS shall be as given below
OOS / XXX /YY/NNN
OOS—- Out of specification
XXX— Product code
YY— Year code (last two digits of calendar year)
NNN— Three-digit sequential number
6.0 TRAINING
Trainer : Head – Quality Assurance
Trainees : Staff of all the departments
7.0 DISTRIBUTION
Master Copy : Quality assurance
Controlled Copy : Quality Assurance
8.0 ATTACHMENT
| Sr. No. | Annexure No. | Title | Format No. |
| 1 | NA | NA | NA |
9.0REFERENCES
In-house
10.0 ABBREVIATION
| Abbreviation | Extended Form |
| EG | Engineering |
| SOP | Standard Operating Procedure |
| QA | Quality Assurance |
| WH | Warehouse |
| NA | Not Applicable |
| MB | Microbiology |
11.0 REVISION HISTORY OF CHANGE
| Sr. No. | Date | Revision Details | Revision No. |
