In Pharmaceutical Industries, Lab Incident investigation and root cause analysis to identify the source of Extraneous peak is very difficult. In most of the cases it is tuff to convince the regulatory auditor that there is no issue with the product quality, if our investigation is not design to rule out all the possibility of product quality genuiness.
Here I am sharing a case study to understand it in a better way.
Note:Before initiation for Lab incident investigation, It should be ensured by Lab incharge that result is not OOS/OOT. If result is OOS/OOT then it should be investigated through the OOS/OOT SOPs.
Is your SOP of Lab incident is enough transparent for " peak area response" percentage of extraneous peak (Except Related substance test) to initiate the event?
Description of Event:
Extraneous peak observed in dissolution test in one unit (other five units have no extraneous peak) .
Results of all 06 units are between 92% to 98% -Limit is NLT 85%(Q). Subject unit result is 96%.
Preliminary investigation:
From preliminary investigation, no laboratory error (i.e.presure fluctuation or re-use of hplc vial etc. ) is identified.
Re-measurement:
Re-measurement from same solution (same vial, refilled vial) is found in line to the initial i. e. same area response of extraneous peak. Hence instrument error and vial filling error is ruled out.
If peak observed in all hypothesis testing then same vial should be run on PDA detector to know about the spectrum of the unknown peak.
Root cause analysis:
From above investigation, it's seems that there is no instrument malfunction and no vial contamination. So from where this extraneous peak came.
Probabilities:
1- From test tube: Is test tube was cleaned before use for collection of sample.
2- From Dissolution bowl: Is dedicated bowl was used and cleaned before use.
3- From basket/paddle: Is dedicated basket/paddle had been used and cleaned before use.
4-From Autosampler tubing of dissolution: Is cleaning cycle followed as per SOP/Cleaning validation recommendation.
5-Is batch was contaminated from previous manufactured product on same equipment.
To rule out 1 to 4 probabilities quality control unit should work and for 5 probability manufacturing investigation required to identify the history of previous product on same equipment and cleaning validation evaluation.
Outcome of above proposed investigation:
Based on above investigation (1to4) if there is any gap, identified, the drugs which are impacted.
Based on manufacturing investigation (point 5) identify the previous manufactured products on same equipment.
Prepare a list of products based on above investigation and run it on PDA detector.
Match the spectra of each product to the spectrum of inital unknown peak.
If spectrum is not match with manufacturing related products, then there is no issue with the product quality.
If spectrum match with any of product from 1to 4 based product list, then take proper CAPA to avoid re-occurence.
If spectrum not match with any of product, even though we can report the results as no impact on principal peak.
In above investigation we can do more brain storming to identify the root cause and CAPA.
Here I am sharing a case study to understand it in a better way.
Note:Before initiation for Lab incident investigation, It should be ensured by Lab incharge that result is not OOS/OOT. If result is OOS/OOT then it should be investigated through the OOS/OOT SOPs.
Is your SOP of Lab incident is enough transparent for " peak area response" percentage of extraneous peak (Except Related substance test) to initiate the event?
Description of Event:
Extraneous peak observed in dissolution test in one unit (other five units have no extraneous peak) .
Results of all 06 units are between 92% to 98% -Limit is NLT 85%(Q). Subject unit result is 96%.
Preliminary investigation:
From preliminary investigation, no laboratory error (i.e.presure fluctuation or re-use of hplc vial etc. ) is identified.
Re-measurement:
Re-measurement from same solution (same vial, refilled vial) is found in line to the initial i. e. same area response of extraneous peak. Hence instrument error and vial filling error is ruled out.
If peak observed in all hypothesis testing then same vial should be run on PDA detector to know about the spectrum of the unknown peak.
Root cause analysis:
From above investigation, it's seems that there is no instrument malfunction and no vial contamination. So from where this extraneous peak came.
Probabilities:
1- From test tube: Is test tube was cleaned before use for collection of sample.
2- From Dissolution bowl: Is dedicated bowl was used and cleaned before use.
3- From basket/paddle: Is dedicated basket/paddle had been used and cleaned before use.
4-From Autosampler tubing of dissolution: Is cleaning cycle followed as per SOP/Cleaning validation recommendation.
5-Is batch was contaminated from previous manufactured product on same equipment.
To rule out 1 to 4 probabilities quality control unit should work and for 5 probability manufacturing investigation required to identify the history of previous product on same equipment and cleaning validation evaluation.
Outcome of above proposed investigation:
Based on above investigation (1to4) if there is any gap, identified, the drugs which are impacted.
Based on manufacturing investigation (point 5) identify the previous manufactured products on same equipment.
Prepare a list of products based on above investigation and run it on PDA detector.
Match the spectra of each product to the spectrum of inital unknown peak.
If spectrum is not match with manufacturing related products, then there is no issue with the product quality.
If spectrum match with any of product from 1to 4 based product list, then take proper CAPA to avoid re-occurence.
If spectrum not match with any of product, even though we can report the results as no impact on principal peak.
In above investigation we can do more brain storming to identify the root cause and CAPA.
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