Bioequivalence and Bioavailability Forum

Dear Ohlbe!

❝ The rationale is not scientific, it's just paranoia. The fear is that the lab could be tempted to repeat the assay if bioequivalence is not demonstrated, particularly for Cmax, to try and get "better" results. No reason to do such a thing in BA trials when developing a new drug.

Well paranoia is a reason you can’t deal with easily. Psychotherapy is not very effective treating ICD-10 F20.0, F22.0, F22.8; I’ve heard some drugs might help?

❝ There is a lot of regulatory paranoia regarding BE trials, but one has to admit that this paranoia is fed by inspection results. Remember the results of French inspections which were presented at the EGA meeting some years ago (2007 I think):

Sure; Lisbon! I’m recycling one of the slides in my lectures (remember: the nice one with the hand-drawn baseline of a low QC sample in order to ‘make’ a batch valid). I’m using the heading “Don’t try to fool inspectors!”

❝ basically, critical observations in half of the dossiers inspected, including fraud or some level of data manipulation in one quarter of the dossiers inspected.

Yes, scary. But these findings should support more inspections, not preventing science. The problem with paranoiacs is that they are so afraid of getting robbed that first they don’t leave the house to go shopping and later don’ leave the bed anymore because they are afraid of breaking a leg.

To quote Dirk Barends: In BE we forget the only important person, the patient!
He/she is a living person, not just α=0.05… To the right is Foucault’s pendulum. We started seeing ‘essential similarity’ from a clinical perspective (leader of the pack: Germany) and ended up with an in vivo dissolution test (measure of pharmaceutical quality: The Netherlands). Hopefully the pendulum will continue swinging.

BTW, C_max is such a lousy PK metric that IMHO, it should be dropped from BE assessments at all – except for drugs/formulations where there are safety/efficacy issues (I want my headache to go away – now!).

It’s time to have another beer together – maybe at one of our Captain’s preferred harbor taverns.