Back to the Top
The following message was posted to: PharmPK
Hello,
I have a question regarding bioequivalence study needed due to
formulation change. Can the bioequivalence study be performed in an
animal model (dog/monkey or other) for a compound in phase I clinical
trial or does it have to be done in the human? If acceptable PK and
PD parameters obtained using an animal model, is it sufficient for
regulatory filing?
Thanking you,
Anila
Back to the Top
hello anila
In my point of view it is useless to perform
bioequivalence studies in animals for those drugs which are for human
use however it could be perform only for those drugs which are for
animals
remember; clinical trials phase 1 always done on human
hope this will help
Back to the Top
Hi Anila
You can perform BE studies on those drugs marketed for human if those
are being used for veterinary use in your country. Because some time
we have to prescribed human drugs in pets etc.
However, just for research such study is useless.
Regards
Ahmad
Back to the Top
The following message was posted to: PharmPK
Anila,
If you are in Phase 1, you probably haven't done any efficacy studies.
Therefore, it doesn't matter if your new formulation is strictly
bioequivalent to the previous one.
Bioequivalence testing is a way to avoid having to redo efficacy trials.
The assumption is efficacy-concentration time profile of one formulation
= efficacy-concentration time profile of the other if the concentration
time profiles are the "same".
If your concern is that a new formulation behaves somewhat similarly to
the old formulation, then you could probably do a small (n=6, 8) trial
but not have to do a formal powering for bioequivalence.
We have not had much luck using animals for new formulation testing.
Susan Shoaf
Otsuka Maryland Res. Inst.
Back to the Top
Dear Anila,
Your question is an interesting one. I am aware of one instance where
bioequivalence study was done in open-chest, anesthetized dogs and
data obtained were used as a part of the IND application in US. We
did this bioequivalence study in dog when the compound was in human
phase I clinical trial. Currently, the compound is in phase IV
clinical trial with new formulation.
Slight differences were observed in the absolute AUC values for the
two formulations, however, the inherent variability of the one-minute
blood concentrations, which impacts the measured Cmax and ultimately
the AUC was seen to be underlying cause. These small variations were
not believed to be biologically meaningful and were within the
criteria for bioequivalence. As you mentioned, we compared PK
parameters and PD responses from two different formulation doses.
Our PK findings were further supported by the PD data as no
statistical differences in any of the hemodynamic responses were found.
Listed below please find three references:
1. Guidance for industry: Statistical approaches to establishing
bioequivalence. Food and drug administration, US department of health
and human services, 2001.
2. Guidance for industry, bioequivalence guidance, FDA, October, 2002.
3. Davies B and Morris T. Physiological parameters in laboratory
animals and humans. Pharmaceutical Res. 10 (7) 1093-5, 1993.
Best regards,
Sue
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)