BE XR OD vs IR BID - which Cmax for IR? [Regulatives / Guidelines]
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)
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]
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]
Complete thread:
- BE XR OD vs IR BID - which Cmax for IR?Nathalie T 2020-05-08 16:40 [Regulatives / Guidelines]
- FDA ER vs. IR: Global Cmax Helmut 2020-05-09 11:54
- FDA ER vs. IR: Global Cmax for Day 1 too? Nathalie T 2020-05-11 15:59
- Global Cmax (MD and SD) Helmut 2020-05-11 17:51
- FDA ER vs. IR: Global Cmax for Day 1 too? Nathalie T 2020-05-11 15:59
- BE XR OD vs IR BID - which Cmax for IR? jag009 2020-05-11 06:29
- BE XR OD vs IR BID - which Cmax for IR on day 1? Nathalie T 2020-05-11 16:02
- BE XR OD vs IR BID - which Cmax for IR on day 1? jag009 2020-05-12 21:16
- BE XR OD vs IR BID - which Cmax for IR on day 1? Nathalie T 2020-05-18 16:23
- BE XR OD vs IR BID - which Cmax for IR on day 1? jag009 2020-05-12 21:16
- BE XR OD vs IR BID - which Cmax for IR on day 1? Nathalie T 2020-05-11 16:02
- FDA ER vs. IR: Global Cmax Helmut 2020-05-09 11:54