Susanh
☆    

Iceland,
2021-08-18 18:38
(1362 d 05:00 ago)

Posting: # 22528
Views: 2,225
 

 Biowaiver and PK linearity - EU [Study As­sess­ment]

Dear all,
I´m involved in the development of an IR generic product for EU submission. There are 2 strengths of the reference product and the SmPC states that the exposure appears to be non-linear. But, I cannot find a dose study in the literature where both strengths are dosed in the same study. So, I did a 3-way pilot study with both strengths of the reference and 1 strength of the test product. ABE analysis on dose-adjusted AUCt of the reference was used to test dose proportionality. And the results showed that the upper CI is just outside the 80-125. On the other hand, if you compare the dose-adjusted means of the AUCt for the 2 strengths the difference is 8%.
The EU guideline for IR states: “Assessment of linearity will consider whether differences in dose-adjusted AUC meet a criterion of ± 25%.”
Can I use this data to argue that PK is linear and a biowaiver for the lower strengths should be accepted?
Any comments/suggestion is greatly appreciated.
UA Flag
Activity
 Admin contact
23,424 posts in 4,927 threads, 1,670 registered users;
167 visitors (0 registered, 167 guests [including 9 identified bots]).
Forum time: 23:39 CEST (Europe/Vienna)

Lack of clarity is always a sign of dishonesty.    Celia Green

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5