Bioequivalence and Bioavailability Forum

Dear smrama,

❝ In long-term stability experiment, only one out of six LQC was within 85-115%

❝       % Bias


❝ QC1   +16.99


❝ QC2   +19.44


❝ QC3   -15.59


❝ QC4   -27.04


❝ QC5    +1.21


❝ QC6   +16.90


❝ % CV   19.13


❝ % Bias  1.99

❝

❝ The %CV at LQC was not within 15%. Still, the results were accepted since the % bias was within 15%.

Mmmm, not an easy question. That's not a common situation and I would not refer blindly to the acceptance criteria in the SOP.

Some questions:
- what were the results at the HQC level: did they pass or fail ? Did you get a high variability also for the HQC ?
- how was the CV at the LQC level during the Q&A batches: borderline, or passing easily ?
- were the 6 values obtained from 6 separate tubes, or were they pipetted from the same tube ? What was the volume of plasma in each tube and the capacity of the tube ?

If the 6 LQC were pipetted from a single tube: one hypothesis is that the sample was insufficiently mixed after thawing and before pipetting. This can happen if the tube was overfilled (not enough air above the sample for the vortex mixer to efficiently mix it). It has been described as a reason for ISR failure.

Overall: there is something wrong here and I would repeat the test. No regulatory authority would blame you for repeating the analysis in this particular situation: the test passes according to your SOP, which is very different from repeating a failed test until it passes. Make sure you document your decision and why you took it.