gtomer
☆    

Israel,
2014-04-09 16:40
(3641 d 08:49 ago)

Posting: # 12799
Views: 5,007
 

 Justifications for discrepancy in dissolution vs. BE study [Dissolution / BCS / IVIVC]

Hi All,

Would value your opinion:

The bioequivalence guide (CPMP/EWP/QWP/1401 Rev 1) requests to perform a dissolution profile comparison at 3 pHs between the test and reference products used in the BE study.
It gives superiority to the BE study results, should the dissolution profiles will not be similar, "However, possible reasons for the discrepancy should be addressed and justified.".

Does anyone know of any investigatory methods or justifications found for such discrepancy, i.e. where reference vs. test found similar in BE study but F2>50 in dissolution?

Many thanks.
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2014-04-10 14:31
(3640 d 10:58 ago)

@ gtomer
Posting: # 12805
Views: 4,173
 

 Justifications for discrepancy in dissolution vs. BE study

Hi gtomer,

in vivo BE overrules any in vitro dissimilarity (as a successful therapeutic equivalence study would over­rule in vivo inequivalence). You should perform the comparative dissolution, but demonstrating in vitro similarity is not necessary. See also this thread.

❝ Does anyone know of any investigatory methods or justifications found for such discrepancy, i.e. where reference vs. test found similar in BE study but F2>50 in dissolution?


I guess you mean ƒ2 <50? Either the dissolution media are not biorelevant (i.e., overdiscriminatory, since BE was proven in vivo) or dissolution is not the driving force for absorption at all (e.g., BCS classes I/IV).

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
jag009
★★★

NJ,
2014-04-11 17:14
(3639 d 08:14 ago)

@ Helmut
Posting: # 12812
Views: 4,070
 

 Justifications for discrepancy in dissolution vs. BE study

Hi Helmut,

❝ ...dissolution is not the driving force for absorption at all (e.g., BCS classes I/IV).


Does it mean that you would have to run experiments to demonstrate the drug is class IV (run both solubility and permeability) assuming no/insufficient literature supports.

Thanks

John
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2014-04-11 17:22
(3639 d 08:07 ago)

@ jag009
Posting: # 12813
Views: 4,136
 

 Personal experiences…

Hi John,

❝ Does it mean that you would have to run experiments to demonstrate the drug is class IV (run both solubility and permeability) assuming no/insufficient literature supports.


I don’t think so – at least I never got a question from a European agency in my studies (passing BE). I simply reported the dissolution at three pHs. I neither calculated ƒ2 nor did I discuss any­thing.

Other experiences?

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
jag009
★★★

NJ,
2014-04-11 19:58
(3639 d 05:30 ago)

@ Helmut
Posting: # 12819
Views: 4,042
 

 Personal experiences…

Hi Helmut,

❝ I don’t think so – at least I never got a question from a European agency in my studies (passing BE). I simply reported the dissolution at three pHs. I neither calculated ƒ2 nor did I discuss any­thing.


❝ Other experiences?


Yes but I need to dig it up :-) Will get back to you. Not class 4 though
We did it just to protect our butt.

John
UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,636 registered users;
79 visitors (0 registered, 79 guests [including 8 identified bots]).
Forum time: 00:29 CET (Europe/Vienna)

Nothing shows a lack of mathematical education more
than an overly precise calculation.    Carl Friedrich Gauß

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