Bioequivalence and Bioavailability Forum

Dear Helmut and NewInPK,

❝ IMHO ISR for a validated method

❝ (stability and freeze-thaw given) will confirm original

❝ results in most cases. What have we gained?

Except for metabolite back-conversion, which is seldom tested during validation ! That's where this ISR business started from, after all. Apart also from lab errors (switching samples), insufficient sample mixing, etc (of course these should not happen if you work properly. But there are some bad labs on this planet too, and many recommendations are made just because of them). IMHO 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). 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 !

❝ I consider GLP death of analytical chemistry.

I would consider GLP applied by QA personnel/auditors/regulatory inspectors knowing nothing about bioanalysis, to be harmful to analytical chemistry. In France we are lucky to have some GLP inspectors who know also about scientific aspects, 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 ? 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 !

Regards
Ohlbe