US (or EU) ANDA: Fail f2 but pass BE? [Regulatives / Guidelines]

posted by wienui  – Germany/Oman, 2022-09-02 01:22 (158 d 21:08 ago) – Posting: # 23259
Views: 1,810

Hi John & all,

❝ A question, has anyone ever filed an ANDA with great BE study results (90% Cmax and AUC ~ 98-100%, adequate sample size, ISCV~25%) but with f2 << 50 (F2=30 due to differences in very early timepts) in the comparative dissolution study based on method recommended in the BE guidance for IR product?


normally, In vivo study over­rules in vitro dissolution study i.e, even if f2 doesn't show the similarity between the test & reference formulations, the two formulations are considered as therapeutic equivalence.

❝ 1) F2 is not really applicable for IR, correct? The sampling timepts were 5, 10 ,20, 30, 45mins. I know that f2 is not really relevant if % dissolve > 85% in 15 mins, but my product is >85% after 20 mins..


What about if you start with sampling time points @ 10 min ( EMA) and not @ 5min ( FDA)?
have you tried with bootstrapping to overcome the high variability in the early sampling time points?

❝ 2) is f2 based on guidance recommendation even relevant if the BE results are so good?


f2 is a supportive in vitro method to the in Vivo crucial BE study to prove the therapeutic equivalence.

Cheers,
Osama

Complete thread:

UA Flag
Activity
 Admin contact
22,485 posts in 4,710 threads, 1,603 registered users;
29 visitors (0 registered, 29 guests [including 15 identified bots]).
Forum time: 21:30 CET (Europe/Vienna)

The difference between a surrogate and a true endpoint
is like the difference between a cheque and cash.
You can get the cheque earlier but then,
of course, it might bounce.    Stephen Senn

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