relax [Regulatives / Guidelines]
Hi Fabrice,
An example: The NDA of idelalisib. A lot of Phase I/II studies (women/men, Japanese/Caucasian, food effect, DDIs, renal/hepatic impairment) were performed in 6 (six!) to 12 subjects with early formulations.
There was also a study comparing formulations (n = 15, extremely underpowered for the x̃ CV of 29% in earlier studies). Some comparisons failed (e.g., 90% CI of Cmax 106–153%). Funny:
Since idelalisib is in BCS II (where dissolution cannot predict in vivo performance), the FDA lamented about later manufacturing changes but accepted the package at the end of the day.
❝ ❝ Doesn’t matter because we are interested in PK (I) and safety (II).
❝
❝ OK but then how to justify in the dossier the extrapolation of some early phase outcomes, e.g. a food effect or an efficacy and/or safety exposure signal... should these key findings be evaluated/demonstrated again with the final formulation?
An example: The NDA of idelalisib. A lot of Phase I/II studies (women/men, Japanese/Caucasian, food effect, DDIs, renal/hepatic impairment) were performed in 6 (six!) to 12 subjects with early formulations.
There was also a study comparing formulations (n = 15, extremely underpowered for the x̃ CV of 29% in earlier studies). Some comparisons failed (e.g., 90% CI of Cmax 106–153%). Funny:
2.5.2.2 What are the safety or efficacy issues, if any, for BE studies that fail to meet the 90% CI using equivalence limits of 80–125%?
None. The exposure for the different drug products is similar.
Since idelalisib is in BCS II (where dissolution cannot predict in vivo performance), the FDA lamented about later manufacturing changes but accepted the package at the end of the day.
—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- FDA: required BE between early phase and Phase 3 formulations? fno 2020-01-22 15:38 [Regulatives / Guidelines]
- no BE between early phase and Phase 3 formulations Helmut 2020-01-22 16:15
- no BE between early phase and Phase 3 formulations fno 2020-01-22 17:11
- relaxHelmut 2020-01-23 11:59
- Thanks! fno 2020-01-23 14:48
- relaxHelmut 2020-01-23 11:59
- no BE between early phase and Phase 3 formulations fno 2020-01-22 17:11
- FDA: required BE between early phase and Phase 3 formulations? Achievwin 2020-01-27 20:06
- no BE between early phase and Phase 3 formulations Helmut 2020-01-22 16:15