Here we will discuss about an OOS of destructive test (Water content test by Karl Fischer) . In other case of OOS we can do the many of hypothesis testing to identify the root cause, but in distructive test we can not produce the same situation again.
Description of Event:
OOS result observed in Water content test.
Result: 4.9% .
Limit: NMT 4.0%.
Preliminary Investigation:
During preliminary investigation, checked all the possibilities of higher water content result like any leakage in vessel, graph pattern, delay in analysis after crushing of tablets etc., but no any error is identified from preliminary investigation.
Re-measurement:
Destructive test , hence not possible.
Trend evaluation:
Reviewed all batches data which are manufactured in last 2years, and all water content results are found between 1.5% to 2.0%.
So there is no trend of higher water content.
Re-analysis:
Can we perform the re-analysis based on trend ?, and if result is with in the specification limit and trend of other batches, can we release the batch?
My Take:
Yes, we can perform the re-analysis based on trend data, and release the batch.
But, what is missing in this investigation, what additional we can do to make this investigation more adequate.
As per my opinion, in above investigation if we perform a protocol base study as an expanded hypothesis I. e. Prepare a protocol to perform sample analysis in 3-sets and maximum variation between lower and higher results should not be more than 0.5%.(why 0.5%--In last 2years data the variation in results are only 0.5% it means product give very consistent results) .
If any set of result is failed or near to 4.0%, then we can not perform the re-analysis and send the investigation for Phase-II.
But if results are complying to our Pre-approved acceptance criteria of protocol then definitely we can perform the re-analysis.
Re-analysis results found well with in specification limit and trend.
So what is the root cause for initial higher result.
Now we can compare graph pattern of initial, hypothesis and re-analysis results, is there any difference in the pattern of initial analysis.
Call and Discuss the case with Technical person (Technical engineer) of Instrument with all these data, definitely you will get the root cause or the most probable root cause.
In this case we have to perform the phase-II investigation to check variation (if any) from previously manufactured batches.
Our above efforts will give confidence to auditor.
Description of Event:
OOS result observed in Water content test.
Result: 4.9% .
Limit: NMT 4.0%.
Preliminary Investigation:
During preliminary investigation, checked all the possibilities of higher water content result like any leakage in vessel, graph pattern, delay in analysis after crushing of tablets etc., but no any error is identified from preliminary investigation.
Re-measurement:
Destructive test , hence not possible.
Trend evaluation:
Reviewed all batches data which are manufactured in last 2years, and all water content results are found between 1.5% to 2.0%.
So there is no trend of higher water content.
Re-analysis:
Can we perform the re-analysis based on trend ?, and if result is with in the specification limit and trend of other batches, can we release the batch?
My Take:
Yes, we can perform the re-analysis based on trend data, and release the batch.
But, what is missing in this investigation, what additional we can do to make this investigation more adequate.
As per my opinion, in above investigation if we perform a protocol base study as an expanded hypothesis I. e. Prepare a protocol to perform sample analysis in 3-sets and maximum variation between lower and higher results should not be more than 0.5%.(why 0.5%--In last 2years data the variation in results are only 0.5% it means product give very consistent results) .
If any set of result is failed or near to 4.0%, then we can not perform the re-analysis and send the investigation for Phase-II.
But if results are complying to our Pre-approved acceptance criteria of protocol then definitely we can perform the re-analysis.
Re-analysis results found well with in specification limit and trend.
So what is the root cause for initial higher result.
Now we can compare graph pattern of initial, hypothesis and re-analysis results, is there any difference in the pattern of initial analysis.
Call and Discuss the case with Technical person (Technical engineer) of Instrument with all these data, definitely you will get the root cause or the most probable root cause.
In this case we have to perform the phase-II investigation to check variation (if any) from previously manufactured batches.
Our above efforts will give confidence to auditor.
Even if there is a consistency in 3 runs as per protocol we can not invalidate initial OOS..
ReplyDeleteAs per guideline we should perform manufacturer and sampling assessment for impacted batch then will extend to PIIb for 3/6replicates( as per SOP).
Then we can extract potential causes by applying coginitative tools and invalidate initial OOS.
Full scale investigation mandatory for this case.