Bioequivalence and Bioavailability Forum

Hi Luv,

❝ I am now more worried about the variability in fed condition where there will be more variables (different gastric pHs, different gastric emptying rate, different gastric moment). Innovator has not done the fed study but FDA want generics company to do both the studies (here)

That’s bizarre, IMHO. I didn’t look in the label but in Europe the SmPC states something like “to be taken on an empty stomach one hour before meals”.*

❝ With this variability, does it really makes a sense to run a pilot study using 18-24 volunteer?? As there will be no gurantee that a product formula comfortable in pilot will pass again in pivotal studies.

Likely. We face this problem all the time when we plan pivotal studies. If scaling is concerned, the CV is not problematic, but the GMR really may hurt. With such a high CV, I have some doubts whether you’ll get a meaningful estimate of the GMR from the pilot at all. Follow your gut feelings (mesalamine…).

❝ Or one shall simplay go ahead with the exhibit batches and take a rist with higher number of volunteers?

Duno. Ask a fortune-teller.

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• Must correct myself: Neither the US label of the new formulation nor the SmPC in Europe (the “old” formulation is still on the market) contain a statement about food intake. So the recommendation of fasting/fed is in line with what regulators generally want to see for MR-products. Yes, innovators might be treated differently (at least by the FDA).