Bioequivalence and Bioavailability Forum

Dear Ohlbe!

❝ ❝ IMHO ISR for a validated method [...]

❝ Except for metabolite back-conversion, which is seldom tested during

❝ validation !

Very true.

❝ That's where this ISR business started from, after all.

Oh, I didn't know that! Thanks for the historical perspective.

❝ [...] ISR is a bad answer to a real problem, as it will only give you

❝ information on between-run precision, but no information on accuracy

❝ (your method could be consistently wrong).

Exactly. The concept of accuracy in bioanalytics is current only seen within the framework of a particular method. If I remember it correctly in forensics two different methods had to applied to provide legal acceptable evidence. In the late 1970ies (the dawn of GC-MS) this requirement was relaxed, since everybody started to believe in high selectivity...

❝ Unfortunately nobody came up with a better suggestion... apart from

❝ NewInPK in his post, which would bring him many enemies in this business

❝ if it were to be implemented !

Yes, he/she is courageous - but the arguments are scientifically quite strong.

❝ ❝ I consider GLP death of analytical chemistry.

❝ [...] In France we are lucky to have some GLP inspectors who know also

❝ about scientific aspects,

I know at least one.

❝ [...] and who like study personnel to use their brains, and not just follow

❝ the SOPs.

❝ ❝ Since in most cases an alternative method is not available, it's a good

❝ ❝ idea to challenge the one we have - far beyond robustness/ruggedness...

❝ Agreed. But doesn't it mean you have to validate your alternative method

❝ too ?

Only to some extend. Forget about stability, freeze-thaw-cycles, bla bla; a partial validation should do the job. Since we are in the wide field of heresy now, I would even skip batch-to-batch accuracy/precision and only check linearity, LLOQ, and a set of QCs. That's one day work for the validation and another one for NewInPK's samples...

❝ Twice the cost and time... And who's going to pay: the lab, or the

❝ sponsor ? There are already some discussions between some sponsors and the

❝ CROs about ISR, as the sponsors say that ISR is part of validation !

Costs are subjected to negotiations. The question is: are we really interested in getting (more) reliable results?