The pharma industry typically sets 2 limits for assay. For example, if the pharmacopoeial limit is 95 %-105 %, they will set a release limit of 97.5% - 102.5%. Now, if the product does not meet the release limit but the pharmacopoeial limit (eg, 96.5%), what to decide for this product? what kinds of documentation are required?
Of course, this is the OOS (Out of specification) Test result, hence need a full investigation to find out the root cause of assy failure for the release limit. Whether it’s an Analyst / QC lab-related error or a manufacturing error (Operator or process-related error). A thorough investigation should be carried out.
QA has to take a final call to release the batch under deviation considering its impact on the shelf-life requirement of the assay (based on stability studies data and risk assessment)
But should I call it OOS or OOT? Technically it is within the pharmacopoeial limit.
This is indeed out of specification (OOS as per in-house specification).
There is no relevance of the Pharmacopoeial limit here because you have Inhouse specification, which is more stringent than the Pharmacopoeial limits.
OOT is considered only when the results are still within the limit (passing) but out of the usual trend compared to the previous batches results.
In your case the result can not be considered as OOT because it is NOT PASSING as per Inhouse specification.
Please note that generally pharmacopoeial limits are given for stability (as shelf life specification). At the time of batch release, the specification should be more stringent than that of pharmacopoeial limits. This is to ensure that the product will be within specification limits up to its shelf life (within the expiry period).
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If I raise an OOS, can I release that batch? How to approach that batch?
Yes please. Your QA Head should decide to release the batch with appropriate investigation and risk assessment. The low assay should not affect the batch quality until its expiry date (Shelf life).
sunilrbudhkar: Sir, Can you tell me what investigation and risk assessment approach I need to take to release that batch?
To conclude the investigation, the results should be evaluated, the batch quality should be determined, and the Quality Unit (QA) should make a release decision. The relevant SOPs should be followed in arriving at this point. Once a batch has been rejected, there is no limit to further testing to determine the cause of the failure so that corrective action can be taken.
The Quality Unit (QA) is responsible for interpreting the investigation results. An initial OOS result does not necessarily mean the subject batch fails and must be rejected. The OOS result should be investigated, and the findings of the investigation, including retest results, should be interpreted to evaluate the batch and reach a decision regarding release or rejection.
In those cases where the investigation indicates an OOS result is caused by a factor affecting the batch quality (i.e., an OOS result is confirmed), the result should be used in evaluating the quality of the batch or lot. A confirmed OOS result indicates that the batch does not meet established standards or specifications and should result in the batch’s rejection, and proper disposition. For inconclusive investigations — in cases where an investigation
(1) does not reveal a cause for the OOS test result and
(2) does not confirm the OOS result — the OOS result should be given full consideration in the batch or lot disposition decision.
Any decision to release a batch, despite an initial OOS result that has not been invalidated, should come only after a full investigation has shown that the OOS result does not reflect the quality of the batch (Including stability studies considered for this product). In making such a decision, the Quality Unit (QA) should always err on the side of caution.
Please refer to the USFDA guidance on Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production - May 2022.
Thanks for your kind reply
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