Bioequivalence and Bioavailability Forum

Thanks HS for reply,

❝ are you aware of FDA’s guidance?

Yes I saw that but since it is still in draft phase (old-2006) wanted to confirm with practical experience

❝ ❝ 1. Is it mandatory for USFDA that Cmax, AUC meet the traditional BE limits of 80 - 125 for claiming no DDI?

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1. If you have a PK/PD model you can set the “no effect boundaries” on it.
   

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2. If not, 80–125% apply.

❝ ❝ 2. If the study fails for meet 80-125 limits, is it possible to justify on clinical grounds that such an effect is of no clinical relevance?

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❝ If you follow approach 2 above you should design the study with a sufficiently large samples size.

Ok. This is from draft guidance

❝ ❝ 3. How to calculate sample size of DDI studies?

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❝ Based on the drug with the larger CV_intra and the “no effect boundaries”.

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❝ ❝ 4. Since all the three products are developed by us on the same platform, we can assume zero / minimal variability associated with formulation difference.

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We are sure that there shall be no/very less variability due to formulation as all the three products are manufactured by us on same platform with same excipients/process/manufacturing location, which is not the case in BE study as Test and reference product are based on different platforms/manufacturing process/location etc. Hence we want to remove this variability part from total variability while calculating sample size

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❝ ❝ Is there any method to calculate the sample size based on true intrinsic variability of molecule only? This can reduce our sample size to some extent.

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❝ Doesn’t make sense. You administer formulations, not the APIs in solution.

Explained above