Bioequivalence and Bioavailability Forum

Hello Tina,

❝ I am currently working on an IR generic product.The reference comparator SPC mentions no information of PK differences and meals. SD fed and fasted study was conducted for EU submission. The fasted study failed while the fed study passed. Though the product was developed as a generic 10(1), can the difference observed in the result be submitted as hybrid generic application and have specific wording in the SPC for taking the generic developed product with or after meals? Is this option acceptable?

A 10.3 application is not a good way forward for you. Your problem is that it is easily argued that bioavailability studies are 'appropriate' (check the exact wording in 10.1 and 10.2). If you submit as 10.3 then you should provide preclinical tests or clinical trials so you would need to argue that your PK was a good surrogate for clinical trials which in itself would likely speak against a shift from 10.1/10.2 to 10.3.

I'd be interested to hear how the fasted study failed. Was the CI completely outside the acceptance range? If it was then you are in my opinion close to gameover. If there is a partial overlap you might be in a situation where you could justify another trial depending on the details.

Hi Tina,

❝ I am currently working on an IR generic product.The reference comparator SPC mentions no information of PK differences and meals. SD fed and fasted study was conducted for EU submission.

According to EMA's guideline, for IR formulation if the reference, according to its SPC, can be taken irrespective of meal (I assume this is the case based on your description) then only 1 fasting study would be enough. I'm interested to know why you did fed study as well?

As for your question ElMaestro has already answered.