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Dear Members,
This in reference to a Bioequivalence Study carried out under fed
state. Although the study is passing the 90% Confidence Interval
criteria (for Cmax and AUC) but in 3 volunteers (out of the total of
48) the first sampling point (15 min) itself is observed to be the
Cmax. In all the other volunteers, the requirement of at least 3
sampling points before the Cmax is comfortably met. This is mainly
due to the highly variable and unpredictable absorption behavior of
the drug.
My query is whether these 'First Point Cmax' are acceptable to the
regulatory agencies or would ask for some justification.
Thanking you in advance.
Regards,
Hitesh Maheshwari
Hikma Pharmaceuticals
Amman, JORDAN
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The following message was posted to: PharmPK
Dear Mr. Hitesh,
I predict the median Tmax of your study is one hour, the sampling
schedule
may be 15 minutes interval upto 2 hours and the intrasubject
variability is
above 30%. The question is whether 'First Point Cmax' is observed
for both
test and reference products in the three subjects or not and type
of the
dosage form used for BE study?
I hope the regulatory authorities may accept your study because as
per your
information for a such highly variable and rapidly absorbed drug,
if you
sample the study with 10 minutes interval also what is the
guarantee that
no subject will show 10 minutes time point as 'First Point Cmax'.?
If your study passes with or without these three subjects, I hope
it is
acceptable to regulatory authorities without any justification.
With Regards,
V.Radhakrishna
Clinical Pharmacology and Pharmacokinetics
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Hi Hitesh,
I have faced similar situations earlier during my compliance audit
for one of our drug product. The Cmax/Tmax is natural to give
variations, even sometimes very peculiar. It is because Cmax/Tmax is
diractly propotional to the demographic variations of subjects and
the characteristics of the drug product formulations. As long as your
acceptance criteria are met, there is no issue from Regulatory aspects.
Your CI is 90% as you are saying.
Hope this answars your question.
Warm regards
Subas Chandra Mohapatra
Regulatory Compliance
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