Type I error inflation caused by batch-to-batch variability of Reference? [Design Issues]
Hi
If a RLD shows such a high in-vivo batch-to-batch variability, why should this be the problem of the generic industry?
From a regulatory point of view I would say that a batch-to-batch variability which leads to bio-in-equivalence of batches of the same product is a serious risk to public health and the product should not be approvable (how can you transfer the safety and efficacy results gained with clinical batches to marketed batches/product?). IMHO the originator should be obliged to change the product specification and demonstrate bioequivalence within his formulation.
However, if such a RLD is notwithstanding approvable then high batch-to-batch variability should not matter, right? Otherwise the logic consequence would be
alternative 1: that generics need to show bioequivalence to each originator batch, or
alternative 2: do not need to show bioequivalence at all.
In the 2015 Meeting Report entitled “Pharmacokinetics of Orally Inhaled Drug Products” a recommendation seemingly attributed to an FDA speaker states “To include batch-to-batch and intra-subject variability of the reference product, the comparison of one batch of the test product with two batches of the R product, with one R batch being repeated, was suggested.”
hmmm, if the two R products are not bioequivalent, what would be the advantage of such a design?
I guess this will lead to interesting discussions....
If a RLD shows such a high in-vivo batch-to-batch variability, why should this be the problem of the generic industry?
From a regulatory point of view I would say that a batch-to-batch variability which leads to bio-in-equivalence of batches of the same product is a serious risk to public health and the product should not be approvable (how can you transfer the safety and efficacy results gained with clinical batches to marketed batches/product?). IMHO the originator should be obliged to change the product specification and demonstrate bioequivalence within his formulation.
However, if such a RLD is notwithstanding approvable then high batch-to-batch variability should not matter, right? Otherwise the logic consequence would be
alternative 1: that generics need to show bioequivalence to each originator batch, or
alternative 2: do not need to show bioequivalence at all.
In the 2015 Meeting Report entitled “Pharmacokinetics of Orally Inhaled Drug Products” a recommendation seemingly attributed to an FDA speaker states “To include batch-to-batch and intra-subject variability of the reference product, the comparison of one batch of the test product with two batches of the R product, with one R batch being repeated, was suggested.”
hmmm, if the two R products are not bioequivalent, what would be the advantage of such a design?
I guess this will lead to interesting discussions....
—
Kind regards and have a nice day
Dr_Dan
Kind regards and have a nice day
Dr_Dan
Complete thread:
- Type I error inflation caused by batch-to-batch variability of Reference? nobody 2016-10-20 10:00 [Design Issues]
- Type I error inflation caused by batch-to-batch variability of Reference?Dr_Dan 2016-10-20 12:06
- Type I error inflation caused by batch-to-batch variability of Reference? nobody 2016-10-20 12:14
- Type I error inflation caused by batch-to-batch variability of Reference? Dr_Dan 2016-10-20 12:20
- Type I error inflation caused by batch-to-batch variability of Reference? nobody 2016-10-20 12:27
- Type I error inflation caused by batch-to-batch variability of Reference? Dr_Dan 2016-10-20 12:49
- Type I error inflation caused by batch-to-batch variability of Reference? nobody 2016-10-20 14:27
- Type I error inflation caused by batch-to-batch variability of Reference? Dr_Dan 2016-10-20 12:49
- Type I error inflation caused by batch-to-batch variability of Reference? nobody 2016-10-20 12:27
- Type I error inflation caused by batch-to-batch variability of Reference? DavidManteigas 2016-10-21 10:44
- Type I error inflation caused by batch-to-batch variability of Reference? Helmut 2016-10-24 17:12
- Type I error inflation caused by batch-to-batch variability of Reference?Dr_Dan 2016-10-20 12:06