Bioequivalence and Bioavailability Forum

Hi Bebac user,

consider section 3.2.1 of M13A Bioequivalence for Immediate-Release Solid Oral Dosage Forms:

For new intended label use/instructions, e.g., ODT as an extension to another orally administered IR drug product, BE studies may be conducted to determine whether the ODT is BE to the comparator product. In this scenario, the ODT product should be administered according to its intended labelling and compared with the comparator product administered as per its labelling.

If the new intended label use/instructions state that the ODT can be taken with and without water, a 3-arm BE study is recommended to demonstrate BE of the ODT administered with and without water compared to the comparator product administered as per its labelling.

In other words, if you want to claim administration without or with water in the label, you have to test both conditions. The IR comparator should be administered as usual with water.

❝ I want to compare two ODT (0.5 mg*2) Vs one conventional tablet (1mg).

Not sure what you mean. Are the two ODT’s different formulations? If yes, you have two options (section 2.2.5.2 of the guideline).

1. If you want to show BE of both to the comparator, you can use the 90% confidence interval. Pro: Smaller sample size than in the second option. Downside: If one fails, the other one is considered a failure as well (even if within the limits).
   
2. If you want to show BE of any of them, i.e., seek market authorisation for the passing one(s), you have to adjust for multiplicity by using the 95% CI.Pro: You get two chances. Downside: Larger sample size than in the first option.

❝ Single dose, two treatments, two periods under fasting conditions

You have three products and therefore, a 2×2 crossover does not fly. You need a 3×3 Latin Square or a 6×3 Williams’ design. The latter is preferred by regulators.

Dear Bebac User!

❝ How the dosing will be (with or without) water?

❝ Is this right to use odt without water and conventional tab. With 240 ml water ??

Dosing should be with (a) water for ODT and conventional tab and (b) without water for ODT but with water for conventional tablet.

The point (b) is useful to have a label direction that ODT can be taken with or without water.

Regards,
Divyen