Bioequivalence and Bioavailability Forum

AB ☆ India, 2013-01-10 09:42 (4913 d 12:52 ago) Posting: # 9811 Views: 4,183	Scaling approach in steady state [Design Issues] Post reply
	Dear All, Can we adopt a ref scaling approach in a steady state design for highly variable drugs? if yes, in such cases what are the parameters to consider for the scaling for USFDA & EMA submission studies. Many thanks in advance. — Regards, AB

Helmut
★★★

Vienna, Austria,
2013-01-10 14:30
(4913 d 08:04 ago)

@ AB
Posting: # 9814
Views: 3,621

Scaling approach in steady state

Post reply

Dear AB,

❝ Can we adopt a ref scaling approach in a steady state design for highly variable drugs?

Why not?

❝ if yes, in such cases what are the parameters to consider for the scaling for USFDA & EMA submission studies.

Not sure what you mean by “parameters to consider for the scaling”.

PK metrics in steady state are AUC_τ and C_max,ss.
FDA: RSABE acceptable for AUC and/or C_max if s_WR ≥0.294.
GMR within 0.8–1.25. Minimum sample size 24 (rumor!).
EMA: ABEL acceptable only for C_max if CV_WR >30%; maximum scaling factor limited to 50%.
GMR within 0.8–1.25. Clinical justification required.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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AB ☆ India, 2013-01-11 14:42 (4912 d 07:53 ago) @ Helmut Posting: # 9825 Views: 3,384	Scaling approach in steady state Post reply
	Dear Helmut, Many thanks for your response. “parameters to consider for the scaling”. I mean which PK parameters to consider for the scaling. Along with PK parameters and criteria you mentioned, should we also consider C_min for scaling or not? am not sure to what extent my question is valid. Thanks again — Regards, AB

Helmut
★★★

Vienna, Austria,
2013-01-11 15:11
(4912 d 07:24 ago)

@ AB
Posting: # 9826
Views: 3,472

Only AUCt and Cmin

Post reply

Dear AB!

❝ Along with PK parameters and criteria you mentioned, should we also consider C_min for scaling or not?

According to the [image]

guidance you should report C_min together with C_av, degree of fluctuation [(C_max–C_min)/C_av], and swing [(C_max–C_min)/C_min]. A statistical comparison is not required.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Scaling approach in steady state [Design Issues]

Scaling approach in steady state

Scaling approach in steady state

Only AUCt and Cmin