ANVISA Regulation for NTI [Regulatives / Guidelines]

posted by Sukalpa Biswas – India, 2020-05-26 12:47  – Posting: # 21468
Views: 494

For NTI product for USFDA, we follow product specific guidance where 4WC study is mandatory with statistical criteria discussed below,

Un scaled Average Bioequivalence approach
• Primary pharmacokinetic parameter(s) for the 90% confidence interval of the geometric least square means must fall within 80.00% to 125.00% (both inclusive).
Reference Scaled Average Bioequivalence
• SWR will be determined for Primary pharmacokinetic parameter(s) of Cmax, AUC0-t and AUC0-∞.
The following criteria will be estimated for Primary pharmacokinetic parameter(s):
• The 95% upper confidence bound for (μT-μR)2-θ*S2WR must be ≤ 0
Where μT and μRare mean of test and reference formulations on ln-transformed scale, respectively, and θ = (In (1.11111)/ (σW0)2 (Scaled average BE limit); where σW0 = 0.10 (regulatory limit).
• The point estimate of the Test/Reference geometric mean ratio must fall within [0.80, 1.25] 90% CI for the ratio of the within subject SD of Test product to Reference product σWT/σWR
• The within-subject standard deviation of test and reference products will be compared, and the upper limit of the 90% confidence interval for the test-to-reference ratio of the within-subject variability should be ≤ 2.5.


For NTI product of ANVISA studies,
1. if 95% CI need to be ensured within 80-125, then can we prefer doing 2WCstudies(ISCV<30%)?
2. If ISCV>30%, can we go for full replicate/partial replicate design? If yes then what will be the statistical approach?
3. Is it necessary to get the statistical approach approved from ANVISA regulatory prior initiation of the study.


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