In Pharmaceutical Industries OOS investigation and root cause identification is very important topic. If you are not able to identify the exact root cause, then your effort should be looked in your investigation.
Here I am sharing another case study to understand it in a better way-
Description of Event:
OOS result observed in dissolution test for capsules analysis.
One unit result is 58% and other 5-units are well with in limit (about 98%) -Limit is NLT 85%(Q).
Preliminary investigation:
During preliminary investigation no obvious error is identified, but out of six units, one unit weight is about 40 mg less (subjected unit) in compare to other units weight (about 100mg) .
Re-measurement:
Re-measurement from same solution (same vial, refilled vial) is found in line to the initial result. Hence instrument error and vial filling error is ruled out.
Root cause:
From above investigation, it's seems that as lower weight of capsule is the reason for lower result. It's may be the our first root cause. But how such lower unit capsule has been packed. We have to find out second root cause to make this investigation more adequate.
In such case Phase-II investigation is required.
The manufacturing facility is fully automated and having different check points including sensor to reject the unit of less or higher weight of Pre-defined setting in machine.
But now the question is how such lower weight unit has been packed, if we have sufficient technology to avoid such incident.
If we unable to identify the second root cause then the whole system is questionable.
My take:
In capsule filling it's general observation that many Capsules are rejected due to lower or higher content filling.
But if capsules having lower content but weight is with in range then it will not rejected by the machine.
But the question is how it's possible.. .. It's possible only when lower content capsule have double capping (it's observed when capsule rejected by machine due to higher weight is some time it's double capping) .
So if the above mentioned case is correct then why QC analyst had found lower weight of subjected capsule... .. .. It's may happen the second capping is detached during packing due to vibration which occured during packing for movement of capsules.
If we can do such negative challenge by video recording, then only we can justify the above probability to make this investigation more adequate.
Here I am sharing another case study to understand it in a better way-
Description of Event:
OOS result observed in dissolution test for capsules analysis.
One unit result is 58% and other 5-units are well with in limit (about 98%) -Limit is NLT 85%(Q).
Preliminary investigation:
During preliminary investigation no obvious error is identified, but out of six units, one unit weight is about 40 mg less (subjected unit) in compare to other units weight (about 100mg) .
Re-measurement:
Re-measurement from same solution (same vial, refilled vial) is found in line to the initial result. Hence instrument error and vial filling error is ruled out.
Root cause:
From above investigation, it's seems that as lower weight of capsule is the reason for lower result. It's may be the our first root cause. But how such lower unit capsule has been packed. We have to find out second root cause to make this investigation more adequate.
In such case Phase-II investigation is required.
The manufacturing facility is fully automated and having different check points including sensor to reject the unit of less or higher weight of Pre-defined setting in machine.
But now the question is how such lower weight unit has been packed, if we have sufficient technology to avoid such incident.
If we unable to identify the second root cause then the whole system is questionable.
My take:
In capsule filling it's general observation that many Capsules are rejected due to lower or higher content filling.
But if capsules having lower content but weight is with in range then it will not rejected by the machine.
But the question is how it's possible.. .. It's possible only when lower content capsule have double capping (it's observed when capsule rejected by machine due to higher weight is some time it's double capping) .
So if the above mentioned case is correct then why QC analyst had found lower weight of subjected capsule... .. .. It's may happen the second capping is detached during packing due to vibration which occured during packing for movement of capsules.
If we can do such negative challenge by video recording, then only we can justify the above probability to make this investigation more adequate.
My comments:
ReplyDeleteThere is no first and second root cause.
The cause is identified with evidences for the OOS is the root cause.
If lab did not have any error ( weighing/ handling) it should be manufacturing issue. If capsules were not passing through check wear, this should have occurs.
Impacted batch must be rejected/ recalled and appropriate CAPA must be part of the investigation.
Nice
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