## Significant difference in Cmax of Reference drug product [Study As­sess­ment]

Hi Mehul,

» Can anybody please tell what may be the probable reasons behind significant (more than 20%) difference in mean Cmax concentration of Reference product of a same batch number in two different studies conducted at same CRO and on the similar kind of population but different sample size?

I guess you had also the same batch of the test? Was the AUC different as well?

» Is it correct to compare and expect Reference product's behavior same for all repeated studies?

A few reference products (dasatinib is an infamous example) show extreme batch-to-batch variability. However, generally batches are expected to be similar.
You could compare the references of the two studies as a paired design (assuming to period effects). For a quick estimate calculate $$\small{\widehat{PE}=PE_1/PE_2}$$, with $$\small{PE_1=\frac{T}{R_1}}$$ and $$\small{PE_2=\frac{T}{R_2}}$$, where $$\small{R_1}$$ and $$\small{PE_1=\frac{T}{R_2}}$$ are the reference batches of the two studies.

» […] Can 6 months old (frozen) samples yield significant different results as compared to freshly analyzed study samples?

If long term storage was validated for this duration, no.

Dif-tor heh smusma 🖖
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

21,854 posts in 4,573 threads, 1,554 registered users;
online 10 (0 registered, 10 guests [including 9 identified bots]).
Forum time: Thursday 08:31 CET (Europe/Vienna)

Try to learn something about everything
and everything about something.    Thomas Henry Huxley

The Bioequivalence and Bioavailability Forum is hosted by
Ing. Helmut Schütz