Bioequivalence and Bioavailability Forum

Dear Chiku!

❝ We are developing XR generic formulation (market US). Our formulation is bioequivalent as well as F2 value is matching in all the required dissolution mediums.

❝ The problem is we are failing in alcohol dose dumping study in 0.1 N HCl. what is the way out in this situation? wether regulatory (US FDA) will accept the dossier. Any justification can be provided?

Did FDA publish a product-specific guidance? In vitro testing for alcohol induced dose dumping is not a general requirement – only in specific cases (like Oxycodone ER).

❝ I get to understand EU's thinking but still confused about FDA's thinking. product developed is not opioid in this case.

See above. If there are no safety concerns I would not bother too much.

❝ In our case F2 value is not matching few other statistical methods for dissolution calculation shows similarity.

In the first sentence you said f₂ ‘is matching in all the required dissolution mediums’. Do you mean: passing f₂ in conventional media and failing in testing alcohol induced dose dumping?

❝ […] based on this can i give justification?

Alternative (multivariate) methods like Mahalanobis distance are acceptable for the FDA – if justified (don’t ask me what that means). If you look at the Oxycodone guidance you’ll find a funny statement:

Please conduct comparative dissolution testing on 12 dosage units each of all strengths of the test and reference products. Specifications will be determined upon review of the application.

❝ or else reformulation is the only way out? We used eudragit and Innovator has used HPMC polymer.

Only as a last resort (throwing away the successful BE study). Hypromellose is much less susceptible to alcohol than methacrylic acid / ethyl acrylate copolymer.