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RegisterFDA definition of non-accurately and reliably [Bioanalytics]
Hi everyone,
Can someone clarify this for me... When a FDA draft guidance says bioequivalence is based on the prodrug unless "it is not possible to measure in plasma accurately and reliably", what does it really mean? Does it mean the LoQ has to be low enough? What about the overall variability of the concentration values?
The reason I ask is because I have a prodrug with highly variable concentration values. At the dose I studied in a pilot involving only the reference product, 8-9 out of 24 subjects had almost all BLQs in their entire PK profiles. For these 8-9 subjects, their detectable concentration values are not much higher than the LoQ value). The rest of the subjects are ok with only BLQ values in the last 6 timepoints (24 total). The prodrug is poorly water soluble.
The pivotal study will be dose at 2 x my pilot dose. Assuming linear kinetics and the resulting concentration will be doubled.
Thanks
John
Can someone clarify this for me... When a FDA draft guidance says bioequivalence is based on the prodrug unless "it is not possible to measure in plasma accurately and reliably", what does it really mean? Does it mean the LoQ has to be low enough? What about the overall variability of the concentration values?
The reason I ask is because I have a prodrug with highly variable concentration values. At the dose I studied in a pilot involving only the reference product, 8-9 out of 24 subjects had almost all BLQs in their entire PK profiles. For these 8-9 subjects, their detectable concentration values are not much higher than the LoQ value). The rest of the subjects are ok with only BLQ values in the last 6 timepoints (24 total). The prodrug is poorly water soluble.
The pivotal study will be dose at 2 x my pilot dose. Assuming linear kinetics and the resulting concentration will be doubled.
Thanks
John
Complete thread:
- FDA definition of non-accurately and reliablyjag009 2013-01-09 22:20
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Experiences with EU submissions Helmut 2013-01-10 14:03
- Experiences with EU submissions jag009 2013-01-10 16:36
- Experiences with EU submissions Helmut 2013-01-10 16:56
- Experiences with EU submissions jag009 2013-01-10 20:07
- LLOQ “low enough”? Helmut 2013-01-10 20:46
- LLOQ “low enough”? jag009 2013-01-11 15:20
- LLOQ “low enough”? Ohlbe 2013-01-11 19:16
- LLOQ “low enough”? jag009 2013-01-11 20:14
- LLOQ “low enough”? Ohlbe 2013-01-11 19:16
- LLOQ “low enough”? jag009 2013-01-11 15:20
- LLOQ “low enough”? Helmut 2013-01-10 20:46
- Experiences with EU submissions jag009 2013-01-10 20:07
- Experiences with EU submissions Helmut 2013-01-10 16:56
- Experiences with EU submissions jag009 2013-01-10 16:36
- Experiences with EU submissions Helmut 2013-01-10 14:03
Ing. Helmut Schütz