Back to the Top
The following message was posted to: PharmPK
Hi everyone,
I have added a worksheet to my sample size program that will calculate
the expanded bioequivalence limits based on the FDA discussions at the
Oct 2006 APCS meeting, and the recently published paper available here:
http://www.springerlink.com/content/u503p62056413677/fulltext..pdf
(Haidar S et al, Pharmaceutical Research, Vol. 25, No. 1, January 2008)
The updated version 1.6 of FARTSSIE is available for download in the
same spot:
http://individual.utoronto.ca/ddubins/FARTSSIE.xls
What is different in this version is the worksheet "Scaled BE - HVD".
This worksheet provides easy calculation of the expanded BE limits
based on methods described in the above publication. The results of
every method (except for C3) were verified using the background
document:
http://www.fda.gov/ohrms/dockets/ac/04/briefing/4034B1_07_Bioequivalence%20Requirments-Draft.pdf
(Background Information for Advisory Committee Meeting On April 14,
2004, Bioequivalence Requirements for Highly Variable Drugs and Drug
Products)
If the FDA goes ahead with expanded BE limits based on the reference
variability, what will that do to the bioequivalence limits? Using
their proposed approach (method C2) and the new spreadsheet, I came up
with the following table:
IntraCV of IntraSD Scaled BE Limits
Reference of Reference (Method C2)
30% 0.2936 80.00 - 125.00%
32% 0.3122 78.88 - 126.78%
34% 0.3307 77.77 - 128.58%
36% 0.3491 76.70 - 130.38%
38% 0.3673 75.64 - 132.20%
40% 0.3853 74.62 - 134.02%
42% 0.4031 73.61 - 135.84%
44% 0.4207 72.63 - 137.68%
46% 0.4381 71.68 - 139.51%
48% 0.4553 70.75 - 141..35%
50% 0.4724 69.84 - 143.19%
52% 0.4892 68.95 - 145.04%
54% 0.5058 68.08 - 146.88%
56% 0.5223 67.24 - 148.73%
58% 0..5385 66.41 - 150.57%
60% 0.5545 65.61 - 152.42%
62% 0.5703 64.83 - 154.26%
64% 0.5859 64.06 - 156.10%
66% 0.6013 63.32 - 157.94%
68% 0.6165 62.59 - 159.77%
70% 0.6315 61.88 - 161.60%
72% 0.6463 61.19 - 163.42%
74% 0.6608 60.52 - 165.24%
76% 0.6752 59.86 - 167.06%
78% 0.6894 59.22 - 168.87%
80% 0.7033 58.59 - 170.67%
It will be interesting if/when/how HVD drugs will be treated
differently for FDA submissions. As I have no examples of individual
BE at my disposal, interpret the results of Method C3 with caution. If
anyone knows of an example I can use to verify this calculation, I
would be grateful. A special thanks goes to Helmut Shuetz for posting
the link http://bebac.at/news/2006-10-06.htm, which provided a link to
where the draft document was hiding.
Best,
David Dubins
--
David Dubins, Ph.D., B.Eng.
Global Bioequivalence Consulting
Assistant Professor, Leslie Dan Faculty of Pharmacy
University of Toronto
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Calculation of Expanded BE limits for Highly Variable Drugs added to FARTSSIE" as the subject | Support PharmPK by using the |
Copyright 1995-2011 David W. A. Bourne (david@boomer.org)