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Register90% CI riddle [Bioanalytics]
Dear all
Sorry but IMHO the Q&A document does not help with respect to ISR at all. If the CHMP really follows the spirit of ISR then all of the arguments given in the Q&A document will be rejected.
Regarding the 90% CI riddle: So if you have an overpowered study with a low variable substance you are lucky, because your CI is narrow and if you have a study with a HVD and a low number of subjects then the chance that execution (i.e. switched samples, instrument issues, scientist performance of method), and/or the method (i.e. metabolite interferences, back conversion of metabolites, poor ruggedness, internal standard response) and/or the samples, i.e. matrix effects, mislabelling) handling were inadequate is higher? Ridiculous!
It has to be noted, that the Q&A document points out:"The need for incurred sample reanalysis is discussed already since 20062 and regulators supported the need for incurred sample reanalysis also considering significant bioanalytical deficiencies observed in studies. Therefore, although incurred sample reanalysis is a requirement introduced in Europe for the first time with the new EMA Guideline on bioanalytical method validation (EMEA/CHMP/EWP/192217/2009), which came into force in February 2012, it should be noted that the scientific need to perform ISR as an element of bioanalytical method validation was already identified much earlier."
Furthermore the Q&A document points out that "Abridged applications may exclusively rely on pharmacokinetic data, e.g. bioequivalence studies, making overall validity of these data paramount. Therefore, the validity of the data needs to be considered for the assessment of the application and the specific study considering whether the data are pivotal or supportive."
By this every application for a generic with an "old" BE study can be rejected by retrospective application of the guideline regardless of the scientific justification for missing ISR.
In conclusion I am not convinced that the situation changed to the better
I am looking forward to your opinions
Kind regards
Dan
Sorry but IMHO the Q&A document does not help with respect to ISR at all. If the CHMP really follows the spirit of ISR then all of the arguments given in the Q&A document will be rejected.
Regarding the 90% CI riddle: So if you have an overpowered study with a low variable substance you are lucky, because your CI is narrow and if you have a study with a HVD and a low number of subjects then the chance that execution (i.e. switched samples, instrument issues, scientist performance of method), and/or the method (i.e. metabolite interferences, back conversion of metabolites, poor ruggedness, internal standard response) and/or the samples, i.e. matrix effects, mislabelling) handling were inadequate is higher? Ridiculous!
It has to be noted, that the Q&A document points out:"The need for incurred sample reanalysis is discussed already since 20062 and regulators supported the need for incurred sample reanalysis also considering significant bioanalytical deficiencies observed in studies. Therefore, although incurred sample reanalysis is a requirement introduced in Europe for the first time with the new EMA Guideline on bioanalytical method validation (EMEA/CHMP/EWP/192217/2009), which came into force in February 2012, it should be noted that the scientific need to perform ISR as an element of bioanalytical method validation was already identified much earlier."
Furthermore the Q&A document points out that "Abridged applications may exclusively rely on pharmacokinetic data, e.g. bioequivalence studies, making overall validity of these data paramount. Therefore, the validity of the data needs to be considered for the assessment of the application and the specific study considering whether the data are pivotal or supportive."
By this every application for a generic with an "old" BE study can be rejected by retrospective application of the guideline regardless of the scientific justification for missing ISR.
In conclusion I am not convinced that the situation changed to the better
I am looking forward to your opinions
Kind regards
Dan
—
Kind regards and have a nice day
Dr_Dan
Kind regards and have a nice day
Dr_Dan
Complete thread:
- ISR The Outlaw Torn 2012-11-29 15:58
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- ISR Dr_Dan 2012-11-29 16:30
- ISR The Outlaw Torn 2012-11-30 07:53
- ISR Ohlbe 2012-12-17 22:53
- ISR The Outlaw Torn 2012-12-18 08:09
- 90% CI riddle Helmut 2012-12-18 17:12
- 90% CI riddle The Outlaw Torn 2012-12-19 07:49
- 90% CI riddleDr_Dan 2012-12-20 09:45
- 90% CI riddle The Outlaw Torn 2012-12-20 11:23
- 90% CI riddle Dr_Dan 2012-12-20 12:58
- 90% CI riddle The Outlaw Torn 2012-12-20 11:23
- 90% CI riddleDr_Dan 2012-12-20 09:45
- 90% CI riddle The Outlaw Torn 2012-12-19 07:49
- ISR Dr_Dan 2012-11-29 16:30
Ing. Helmut Schütz