Bioequivalence and Bioavailability Forum

Dear Helmut

❝ Do I get you right: the test used in the BE-study was intentionally formulated to a content 104%? If yes, this was a bad idea. If it was formulated to 100% and only the actual content (analysis of the final product) came out with 104%, nothing to worry about.

You are right it was intentionally formulated with 104% because of stability reasons over shelf life. Now we want to reformulate it 100% by changing some excipients or without changing expicients. If we become successful in achieving stability over shelf life with 100%. Do we need to repeat the bioequivalence?

❝ What BCS Class is your drug in? Should be possible for Classes I & III, and tricky for Class II - impossible for Class IV.

It is practically insoluble in water but has high permeability which means it is BCS class II drug.

Thanks for telling about guideline and your time.

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According to guideline of bioequivalence
Variations
If a product has been reformulated from the formulation initially approved or the manufacturing method has been modified by the manufacturer in the ways that could be considered to impact on the bioavailability, a bioequivalence study is required, unless otherwise justified. Any justification presented should be based upon general considerations, e.g. as per 5.1.1, or on whether an acceptable in vivo/in vitro correlation has been established.
In cases where the bioavailability of the product undergoing change has been investigated and an acceptable correlation between in vivo performance and in vitro dissolution has been established, the requirements for in vivo demonstration of bioequivalence can be waived if the dissolution rate in vitro of the new product is similar to that of the already approved medicinal product under the same test conditions as used to establish correlation

In all other cases bioequivalence studies have to be performed.
For variations of the innovator the reference product for use in bioequivalence and dissolution studies is usually that authorised under the current formula, manufacturing method, packaging etc. and the product manufactured in line with the proposed changes is tested against this.

when variations to an essentially similar product are made the reference product for the bioequivalence study should be the innovator product.


So now my query is that we have bioequivalence with 104% with innovator and if we prove the dissolution rate same as the 104%. Is it possible to waive BE.
As far as I know in vitro correlation can be established for BCS class II.
It means for this product also IVIVC has been established by the innovator and we already have test bioequivalent to the innovator. and then with same dissolution rate as the previous formulation, we can get waiver for BE studies.

please help or suggest, is it possible to avoid BE studies.

Gary

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Edit: Original quotes restored; Section below the horizontal ruler inserted from a later post. @Gary: you may edit your original post for 24 hours - no need to start a new one. [Helmut]