Bioequivalence and Bioavailability Forum

Hi Prashant,

❝ Currently only RLD available is for 25 mg. A couple of years back we performed a pilot biostudy and proved that 10 mg tablets show linear PK and dose proportionality with 25 x 2 dose (two 25 mg tablets administered). But their linear PK data is not available in the public domain.

RLD and EU are mutually exclusive. RLD would be the term you use for US submissions. Do you mean in EU there is no reference product available in the strenght you're wishing to develop?

❝ Now since only 25 mg RLD is available, can i opt the following options to perform biostudy for getting approval for all three strengths:

❝

❝ a. 10 mg x 2 and half tablets vs 25 mg RLD

❝ b. 10 mg x 5 tablets vs 25 x 2 mg RLD

❝ c. 25 mg x 2 tablets vs 25 x 2 mg RLD

❝ d. 25 mg vs 25 mg RLD

❝

❝ Is is there any other option that i can market all the three strengths.

This is not straightforward.
If you can prove to regulators that PK is linear or proportional or whatever the term is (Hötzi, in which direction do the terminological winds blow these days?) then that is perhaps a very good start but I could be a little afraid that it is not necessarily enough.
If there is no ref. in the strength you are developing then I see only art. 10.3. of dir. 2001/83 as your EU submission basis and then we are no longer discussing a true generic. The wording of art. 10.3. specifically mentions a change in strength.
It is an interesting question if you could then first get a 10.1/10.2 (generic) approval for the 25mg formulation and then subsequently introduce the other two strengths via the hybrid article. I am not sure I have a qualified opinion. It could easily require additional trials, I reckon. Otherwise, how could you know if the other strengths are therapeutically efficaceous and safe?
Would like to hear other people's opinion about the regulatory principle. If I were you I would definitely take a scientific advice even if it means some cost and time consumption.