BE XR OD vs IR BID - which Cmax for IR? [Regulatives / Guidelines]

posted by Nathalie T – Belgium, 2020-05-08 14:40 (362 d 06:20 ago) – Posting: # 21409
Views: 2,931

(edited by Nathalie T on 2020-05-08 15:22)

Dear All,
I would like to have the help of the forum participants on a tricky question, ie which IR Cmax should be considered to assess the potential bioequivalence between an IR formulation administered BID and an XR formulation administered OD on day 1 and at steady-state. This is for a submission to FDA.
I double-checked the “Bioavailability Studies Submitted in NDAs or INDs — General Considerations Guidance for Industry” draft February 2019, and it is written (page 13)

C.1.a. A new ER formulation compared to an IR product that is already approved
For drugs with linear pharmacokinetics over the therapeutic dose range: A fasting study should be conducted comparing the ER product administered as a single dose at the highest strength to the IR reference administered over the least common time interval to achieve equivalent total dose as for the ER product.28 […]

28 For example, when a 150-milligram (mg) ER product administered once daily (QD) is being developed that gives an approved 50-mg IR reference product administered three times a day (TID) or a 75-mg product administered two times a day (BID), a comparison of the 150-mg ER product administered as a single dose could be compared to either the 50-mg IR reference product administered TID or 75-mg IR reference product administered BID.

In this case, the least common time interval is 24 hours.

Based on this, I think that the first day dosing interval should be considered as a whole and that on both day 1 and at SS, the highest Cmax over the least common dosing interval should be taken for the reference, whether it is the first or the second Cmax.
I would be very interested of having others opinion
Best regards
Nathalie T

Edit: Guidance linked. [Helmut]

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