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

posted by wienui  – Germany/Oman, 2022-09-02 01:22 (207 d 00:33 ago) – Posting: # 23259
Views: 1,965

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.


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