ANVISA Regulation for NTI [Regulatives / Guidelines]
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.
Edit: Please follow the Forum’s Policy. [Helmut]
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.
Edit: Please follow the Forum’s Policy. [Helmut]
Complete thread:
- ANVISA Regulation for NTISukalpa Biswas 2020-05-26 12:47 [Regulatives / Guidelines]
- ANVISA Regulation for NTI Helmut 2020-05-26 13:39