During OOS investigation root cause is not identified during both phase-I and Phase-II investigation what should be the next step of investigation?
Plz answer for this also.
I think it will be a production investigation.
The QA is responsible for interpreting the results of the investigation. An initial OOS result
does not necessarily mean the 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 take a decision regarding release or rejection.
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 (either to be released or rejected)
In case of inconclusive investigations, the QA might still ultimately decide to release the batch.
If a comprehensive QC laboratory investigation (Phase -1) fails to reveal any laboratory error then carry out further investigation of manufacturing side. Review of events during production of the batch reveals no aberrations, no errors or no indication of unusual process variation. Review of the manufacturing process and product history demonstrates that the process is robust (phase -2 investigation).
The passing retest results are all well within the known limits of variability of the method
used. Batch results from in-process monitoring, content uniformity, dissolution, and other tests
are consistent with the passing retest results. After a thorough investigation, a firm’s QA
might conclude that the initial OOS result did not reflect the true quality of the batch.
It is important in this scenario that the original, thorough laboratory investigation failed to find
any assignable cause. Therefore, subsequent investigation should be carried out. If this investigation also concludes that the source of the OOS result was a cause not related to the manufacturing process.
Hence, it is essential that this investigation should additionally include appropriate follow-up and scrutiny to prevent recurrence of the laboratory error(s) that could have led to the OOS result.
Any decision to release a batch, in spite of an initial OOS result that has not been invalidated (means accepted), should come only after a full investigation has shown that the OOS result does not reflect the quality of the batch. In making such a decision to relaease the batch, QA should always be very careful in taking this decision without any risk or making an error in taking the decision.
As with all analytical testing conducted to evaluate the quality of a drug, all records pertaining to
the OOS test result should be retained. Records must be kept of complete data derived from all
tests performed to ensure compliance with established specifications and standards.
Assay, CU and dissolution at FG stage found OOS (Lowersit) in color part. But no root cause found till now.
Probable root cause are
(1) Improper mixing of color part at blend stage.
(2) Layer weight variations during compression.
Is there any root cause did you know except these.
Please help me out.
Oos is not captured at blend & core stage because our company skipped the testing from mfg. According to trend
@sunilrbudhkar please sir
Since you have already identified probable root cause, please confirm these root causes by hypothesis. Please requeste your production and R & D department to lookinto the matter. Please investigate manufacturing process steps followed for this particular batch, whether any deviations were there? Compare the BMR of this batch with the previous batches for this purpose.