jag009 ★★★ NJ, 2016-05-16 00:26 (2896 d 05:58 ago) Posting: # 16312 Views: 3,685 |
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Hi, Can someone educate me on how FDA chose a value of 0.10 to sigma w0 as the regulatory constant for the scaled reference BE analysis for an NTI drug (see warfarin BE guidance)? I kind of understand why they chose 0.25 for sigma w0 for HVDs but I don't get the reason for NTI. According to the presntation and literature from FDA, 0.1 represents a CV of ~10% Thanks John |
Helmut ★★★ Vienna, Austria, 2016-05-16 16:15 (2895 d 14:09 ago) @ jag009 Posting: # 16315 Views: 3,262 |
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Hi John, ❝ Can someone educate me on how FDA chose a value of 0.10 to sigma w0 as the regulatory constant for the scaled reference BE analysis for an NTI drug (see warfarin BE guidance)? I kind of understand why they chose 0.25 for sigma w0 for HVDs but I don't get the reason for NTI. To harmonize with the EMA’s (fixed) acceptance range for NTIDs of 90.00–111.11%? There is some empiric evidence that it “worked” on this side of the pond. Guidelines of 1992 and 2001: “In specific cases of a narrow therapeutic range the acceptance interval may need to be tightened.” “In specific cases of products with a narrow therapeutic index, the acceptance interval for AUC should be tightened to 90.00-111.11%. Where Cmax is of particular importance for safety, efficacy or drug level monitoring the 90.00-111.11% acceptance interval should also be applied for this parameter.” Don’t forget HC’s 90.0–112.0% for AUC (since 2006).❝ According to the presntation and literature from FDA, 0.1 represents a CV of ~10%. Yep. \(\sigma_0 = 0.1 (CV \sim 10.03\%)\) Therefore, at CVwR 10.03% the scaled AR is 90.00–111.11%. Since this scaling will result in limits wider than the conventional 80–125% for CVwR >21.42% the additional criterion “must pass 80–125%” is part of the method. See also this presentation. — 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 |