Bioequivalence and Bioavailability Forum

Hi Ken,

❝ ❝ It would help to know who told you some­thing. A colleague, a regulator/inspector, the sponsor?

❝

❝ Inspector.

THX for clarifying.

❝ The inspector of the recent inspection is kind enough to accept the use of weighting factor in BE study.

Makes sense.

❝ ❝ You have to stick to what you stated in the protocol. You can recalculate samples as an additional analysis. No idea how regulators like that. In the future, go for a weighted calibration.

❝

❝ The protocol you refer to is study protocol or method validation protocol?

Neither nor. IMHO, the analytical protocol of the study should describe how the calibration will be performed. I think that’s better (and more transparent) than to refer to the method’s SOP.

❝ We do not explain in detail the analytical method in the study protocol, which is submitted to ethical committee.

OK. It is sufficient to submit the goalposts (validated working range, accuracy/precison).

❝ ❝ No. You could use the raw data of the MV and update the validation/SOP.

❝

❝ Kindly explain "update the validation".

The validation consist of the protocol, the actual work, and the report (giving all relevant data necessary to track the outcome). I suggest to write a protocol stating in the purpose something like “Validation of method XYZ by weighted calibration”. Make clear in the method section that you will use the raw data of the original validation. In the report everything will be calculated by the weighted method. You should also update the SOP of the method. If you have a general SOP for calibration, update this one as well.