Bioequivalence and Bioavailability Forum

Dear forum members,

I have questions regarding the calibration curve range considering the statement in "EMEA Guideline on bioanalytical method validation" that says "At least 2 QC sample levels should fall within the range of concentrations measured in study samples". My first question is whether this statement is considered acceptance criteria of each analytical run?

Supposedly, we validated a calibration curve range of 10-100 ng/mL, and LQC is 30, MQC is 50 and HQC is 80 ng/mL. Now please let me set up two scenarios as following.


Scenario 1--- After we analyzed our first batch of study samples, the Cmax are:

subject 1
period 1 is 48 ng/mL
period 2 is 35 ng/mL

subject 2
period 1 is 52 ng/mL
period 2 is 65 ng/mL

subject 3
period 1 is 70 ng/mL
period 2 is 30 ng/mL

Questions:

Since 2 QC levels do not fall within the range of drug concentrations measured from subject 1 (in both periods) and subject 3 (period 2),

1) Is this analytical run accepted?

2) Would you continue with the study or what would you do next?

3) If we continue the study with same curve and QC and the rest of data are somewhat in this trend, can authority reject this study?

Scenario 2---After we analyzed our first batch of study samples, the Cmax are:

subject 1
period 1 is 44 ng/mL
period 2 is 48 ng/mL

subject 2
period 1 is 47 ng/mL
period 2 is 45 ng/mL

subject 3
period 1 is 48 ng/mL
period 2 is 49.5 ng/mL

Similar questions:

Since 2 QC levels do not fall within the range of drug concentrations measured from every subjects,

1) Is this analytical run accepted?

2) Would you continue with the study or what would you do next?

3) If we continue the study with same curve and QC and the rest of data are somewhat in this trend, can authority reject this study?

I really appreciate your time in reading and answering my questions. So sorry for asking similar topic again in this forum but we still having this big issue.

Thank you,
Ladi
(Thailand)

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Edit: Category changed. [Helmut]