Bioequivalence and Bioavailability Forum

Dear Charl!

❝ I do agree with you (if I got your point correctly)

If I expressed myself unclearly – which are the doubtful points?

❝ our cc limits are not the LLOQ - ULOQ, it is 0.8xLLOQ - 1.15xULOQ.

Hhm, we have done this for many years; but it’s a risky business…

❝ why shouldnt we work on this?

Because http://www.fda.gov/cder/guidance/4252fnl.pdf FDA’s guideline (May 2001, Section VI) states:

The calibration (standard) curve should cover the expected unknown sample concentration range in addition to a calibrator sample at LLOQ. Estimation of concentration in unknown samples by extrapolation of standard curves below LLOQ or above the highest standard is not recommended. Instead, the standard curve should be redefined or samples with higher concentration should be diluted and reassayed. (my emphasis)

❝ After all our validation counts for accuracy.

❝ I always argue with this point, but...

I agree with you, but…

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Edit: Link corrected for FDA’s new site. [Helmut]