sop for handling of out of specification results OOS
1.0 OBJECTIVE
1.1 The objective of this SOP is to define the procedure for handling of out of specification results (OOS) generated during the testing of Raw material, packing material, In-process samples, finished product samples and stability samples.
2.0 SCOPE
2.1 This SOP is applicable for handling of out of specification (OOS) test results for In-process & finished product samples, manufactured
3.0 RESPONSIBILITY
3.1 Asst. Officer or above –Quality Assurance – Prepare the SOP and follow-up the SOP accordingly
3.2 Analyst – Responsible for analysis during investigation
3.3 Head – Quality Control – Responsible for Phase I investigation
3.4 Head – Production – Responsible for Phase II investigation
3.5 Asst. Manager –Quality Assurance – Provide the support to the implementation of SOP, Investigation and maintain records.
4.0 ACCOUNTABILITY
4.1 Head – Quality Assurance
5.0 REFERENCE(S)
5.1 In-House
6.0 ENVIRONMENT, HEALTH AND SAFETY
6.1 According to below mention procedure
7.0 PROCEDURE
7.1 All out-of-specification test results (i.e. suspected test results that fall outside the established specifications or acceptance criteria) of raw material, packing material, In-process samples, finished products and Stability samples shall be investigated. (Except microbiological test results which, when does not comply with the specification, are investigated and actions are taken as per respective SOPs.)
7.2 When an Out-Of-Specification test result is generated / suspected, the analyst shall inform to Head QC immediately about the test results.
7.3 Head QC shall inform to Head QA regarding OOS results.
7.4 Each OOS Report shall be assigned a unique alphanumeric number of 10 characters by QA department as OOS/YY/NNN.
Where
First three characters denotes “OOS” stand for “Out of Specification”
The 5th & 6th characters “YY” stand for last two digits of year of manufacturing of the product.
The last three characters “NNN” denote the sequential serial number.
All the groups of characters shall be separated be “/” (hyphen).
7.5 Initial assessment of the results shall be carried out before test and standard solutions are discarded. This shall be carried out according to ‘Initial assessment of OOS results’ as per Format
7.6 If the above assessment indicates that laboratory errors were made and an assignable cause related to laboratory error (like sample preparation, analytical method, equipment, etc.) is established, the analysis is repeated using the initial aliquot of test / standard solutions.
7.7 If the results of re-analysis are within specification, the initial OOS results may be INVALIDATED and cause shall be documented. The sample then can be APPROVED.
7.8 When initial assessment (7.6) does not determine that laboratory error caused the OOS results and testing results appear accurate, a complete full-scale investigation incorporating Phase – I (relating to laboratory error) & Phase – II (relating to manufacturing process) investigations shall be conducted as Format and Format respectively.
7.9 Phase – I investigation shall be carried out according to the steps given in point No. 7.11 to 7.21. If no assignable cause is found in Phase – I investigation and the OOS results are considered to be valid, Phase – II investigation shall be initiated as per the steps given in point No. 7.23 to 7.26.
7.10 Both the analyst and head of department shall be responsible for completion of the Phase – I investigation. This shall be done according to ‘Phase – I Investigation report’.
7.11 Retesting from the original portion of sample drawn shall be performed after due authorization by head of QC. Retesting shall be done by second analyst (in triplicate).
7.12 If all the three results meet the specification and % RSD of the three values is less than 2%, the results may be averaged and reported. The original OOS results can be INVALIDATED and the batch can be APPROVED.
7.13 Cause of original OOS test result shall be investigated. Depending on the nature of analytical error, a review shall be performed to ascertain if such errors have past history. Accordingly, review of analytical method, equipment calibration or re-training of analyst shall be performed.
7.14 Complete review of this investigation shall be documented to prevent recurrence of such incidents in future.
7.15 If the retest also shows OOS results and the subsequent investigation gives possible evidence in respect of errors in sampling (e.g. non-representativeness of original sample indicated by wide variation in results from several aliquots of the original sample), re-sampling permission shall be taken from head of QC.
7.16 Re-sampling, if permitted, shall be performed using the same established sampling procedure.
7.17 Testing of re-sampled aliquot shall be performed by two different analysts, each in triplicate.
7.18 If the six results meet specifications individually, RSD of results for each analyst is less than 2% and difference between the average results of two analysts is less than 2%, original OOS result can be INVALIDATED.
7.19 Further investigation shall be performed to determine reason why the original sample was not representative. If it is established that original OOS results were due to faulty sampling or errors in sampling procedure (like contamination from sampling tool or wrong identification, etc.), then OOS results shall be INVALIDATED. The batch may be considered for RELEASE.
7.20 All steps leading to OOS investigations shall be documented and review of each failure shall be correlated to occurrence of similar failures in the past. An action plan shall then be prepared, depending upon the nature of failure found which caused OOS.
7.21 If no assignable cause is found till this stage and the re-sampling results also do not meet the specifications, the original OOS results shall be considered VALID and subject batch shall be REJECTED. Phase – II investigation shall be initiated.
7.22 The Phase – II investigation shall be carried out by Head QA & Head Production as per ‘Phase – II investigation report’.
7.23 This phase shall take into account the complete evaluation of Batch Manufacturing Record (BMR) related to the subject batch.
7.24 It shall cover complete review / evaluation into potential manufacturing causes of the OOS result and its impact on preceding or succeeding batches of this product.
7.25 Trend analysis of previous batches shall be studied to see if there is any evidence to indicate failures prior to observation of OOS results and also to assess the impact of failure on previous lots.
7.26 Investigation and resolution of all OOS results shall be carried out within 72 hours in case of Phase I investigation. In case of confirmed Phase II investigation to identify the cause of failure, this should be completed within 30 working days and an action plan (to prevent the re-occurrence of the similar test results) should be circulated to all concerned departments.
7.27 General Guidelines
7.27.1 The original OOS result shall not be averaged along with repeat analysis results.
7.27.2 The average of average values reported by individual analyst shall be reported on certificate of analysis.
7.27.3 Investigation report shall outline the corrective actions necessary to release batch if possible and to prevent similar reoccurrence in future.
7.27.4 Investigation shall be extended to other batches and products possibly affected due to process related error if required.
7.27.5 Investigation shall also be extended to other batches and products possibly affected due to operator error or malfunctioning of equipment if required.
7.27.6 If the OOS is caused by analyst error, the analyst shall be retrained. This retraining shall be documented and a copy is to be kept along-with the OOS result.
7.27.7 For dissolution / drug release test out of specification is applicable only if abnormally high or low results are observed, otherwise pharmacopoeial criteria (USP/BP/IP) shall be applied.
7.27.8 If results of uniformity of dosage unit / content uniformity are abnormally high or low, then investigation will be carried out. If assignable cause is identified for OOS then analysis will be repeated by taking adequate precautions and after eliminating the identified assignable cause. After repetition the USP / BP/ IP criteria shall be applied. If no assignable cause observed processed for further analysis as per pharmacopoeia.
7.27.9 If errors are obvious, such as spilling of a sample solution or the incomplete transfer of a sample composite, the analyst should document what had happened. Analysts should not knowingly continue an analysis they expect to invalidate at a later time for an assignable cause (i.e. analysis should not be completed for the sole purpose of seeing what results can be obtained when obvious errors are known).
7.27.10 Part – II of Investing report (related to manufacturing process) shall not to be applicable in the case of stability samples failed.
7.27.11 The log of all “OOS” results shall be maintained as per Format Annual review of “OOS” log shall be carried out wherein similar occurrence shall be reviewed if needed and corrective action should be taken.
7.27.12 Refer flow chart for “Handling of out of specification results” procedure as per Format
8.0 ABBREVIATIONS
SOP : Standard Operating Procedure
QA : Quality Assurance
Mfg. : Manufacturing Date
Exp. : Expiry Date
OOS : Out of Specification
RSD : Relative Standard Deviation
9.0 ANNEXURE
| Annexure No. | Title of Annexure |
| Annexure-I | Flow Chart for Handling of Out of Specification Results |
| Annexure-II | Initial Assessment of OOS Results |
| Annexure-III | Phase – I Investigation Report |
| Annexure-IV | Phase – II Investigation Report |
| Annexure-V | Log Book for Out of Specification |
ANNEXURE
ANNEXURE
ANNEXURE
