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Hi,
FDA states that acceptance criteria for quality controls run for bioanalyses should fall within 85 and 115% nominal concentration AND produce a CV of less than 15%. If both QC's at a level pass, but the CV is greater than 15% (i.e. 20%), does this fail the batch?
Thanks.
Jennifer Norman
Jennifer Norman
QA Manager
Division of Clinical Pharmacology
University of Cape Town
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Yes, that means batch does not meet acceptance criteria.
Even though QCs are within accuracy range , but not meeting %CV criteria means there is no consistency either in extraction or during instrumental analysis.
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Check your SOP. Guidances and numerous white papers permit QC failure. For example if you have six QC, two at each of three levels, you can accept a run so long as only two QC fail and you have at least one surviving QC at each level. IT gets dicey though since you will not have a CV for one level, but...
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thats true
but sometimes situation occures where only 1 set of QC at each level have to be analysed with sample e.g. in case of reanalysis of only one sample, insuch case, if CV is >15% then batch fails for that perticular level of QC.
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By the stated criterion for QC acceptance the purpose is to keep a check on the performance of batch/run i.e. the run is within the acceptance error limits and the variations during extraction/run are not significant. Definitely if this is case for single batch/run, as suggested by guidance document (should abide by to your in-house SOP also) you can accept that batch. But if such variations keep reoccuring then you need to recheck the validation data. Also such high variations will turn up in to huge variations when you will compile/compare the ovarall (study trend analysis) CC and QC data for complete study.
Regards
Kuldeep Sharma
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The following message was posted to: PharmPK
Hi Jennifer,
FDA clearly states that 67 % QC should be within 15 % of nominal value.
As long as both QC of same level or not outside 15 % CV limit, you can
accept the batch.
If I have understood your query right, you are saying that both QC's at
one level or outside 15 % CV, and you got a CV of 20 %. This batch will
fail with the criterion that both QC's of same level cannot be outside
15% CV limit.
Regards,
Vinayak Nadiger
Vinayak Nadiger
Manager, Bioanalytical
Forma Therapeutics(Singapore)
11,Biopolis Way ,Helios # 08-05
Singapore 1386607
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Jennifer: From the 2001 Guidance, there is no restriction on CV for QCs run in a sample analysis run. "The results of the QC samples provide the basis of accepting or rejecting the run.
At least 67% (four out of six) of the QC samples should be within 15% of their respective nominal (theoretical) values; 33% of the QC samples (not all replicates at the same concentration) can be outside the -15% of the nominal value." It is clear that the acceptance is based on BIAS being within range and does not restrict CV. IF you reject one of a pair LQC1, LQC2, then you are without a CV for that level, so that makes sense. Your assya is acceptable.
Do not confuse this CV for the one arising from the use of duplicate results (ELISA) for each QC value,e.g., LQC1 = (LQC1A+LQC1B)/2. That acceptance should be in your SOP.
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