From: "Bonate, Peter, HMR/US" <Peter.Bonate@hmrag.com>
Subject: Bioequivalence question
Date: Fri, 13 Nov 1998 12:16:37 -0600
Does anyone know what the scientific basis for the 80/125 rule in bioequivalence was? Are there any references that discuss why this particular rule was selected?
PETER L. BONATE, PhD.
Population Pharmacokinetics
Hoechst Marion Roussel
POB 9627 (F4-M3112)
Kansas City, MO 64134
phone: 816-966-3723
fax: 816-966-6999
Bioequivalence question
From: LSheiner <lewis@c255.ucsf.edu>
Subject: Re: Bioequivalence question
Date: Fri, 13 Nov 1998 11:06:18 -0800
As I understand it, the original rulewas 80-120, based onthe idea that a 20% deviation would in geenral be biologically unimportant. It was changed to 80-125 to be symmetric on the log scale where most stat tests are done.
From: Chuanpu Hu 301-827-3213 FAX 301-480-2825 <HUC@cder.fda.gov>
Subject: Re: Bioequivalence question
Date: Fri, 13 Nov 1998 14:11:04 -0500 (EDT)
Dear Peter:
The FDA Guidance "Statistical Procedures for Bioequivalence Studies Using A Standard Two-treatment Crossover Design" (July 1992) states that:
"When log-transformed data are used in the analysis of AUC and Cmax, using a range of 80 to 125% for the ratio of averages has an advantage over the 80 to 120% criterion in that for the analysis of log-transformed data, the probability of concluding equivalence is at a maximum if the ratio of averages is in fact 1.0, i.e., exact equality. For the analysis of log-transformed data with a criterion of 80 to 120%, the maximum probability of concluding equivalence occurs when the ratio of product averages equals approximately 0.98. For this reason, the Division of Bioequivalence has decided to use an equivalence criterion of 80 to 125% for the ratio of the product averages."
Hope this helps.
Chuanpu
----------------------------------------------
Chuanpu Hu, Ph.D.
Quantitative Methods and Research
Food and Drug Administration
Room 15B-45
5600 Fishers Lane (HFD-705)
Rockville, MD 20857