Bioequivalence and Bioavailability Forum

Dear Dan,

your example reminds me on the first Arlington conference in 1991. One analyst claimed that he usually runs an entire BE study in one day (ultrafast GC/MS). He was pissed off by the requirement of showing batch-to-batch accuracy/precision (“What the hell? I have only one batch!”). Ended up as a fabulous shouting match with Vinod Shah.

❝ Do you agree with these considerations?

Partly.

• Following Ohlbe’s arguments, no. At the EPF/EUFEPS workshop in Brussels 2010 it was agreed that the first study failing ISR should not lead to rejection of the application – the issue should be investigated and resolved for subsequents ones (GL: “In case incurred sample analysis showed deviating results, this should be investigated, and adequate steps should be taken to minimize inaccuracy (and imprecision).”).
  If this is regulatory practice (duno) the same logic IMHO should be applicable to old studies lacking ISR at all.
  
• If (!) you can guarantee that you don’t have the metabolite issues Ohlbe mentioned, yes. A method is only validated with spiked samples. If the first study with a method passes ISR I – still – don’t understand the requirement to show ISR for subsequent ones with the same method.