ANVISA’s home brewed scaling? [RSABE / ABEL]
recently I saw a response to a request of one of my clients concerning reference-scaling:
“In consideration of your request, we clarify that the Anvisa has accepted the use of the statistical method for scaling proposed by the European Agency (EMA, 2010), with the exception that for Anvisa scaling can only be applied […] in the cases that the intra-subject coefficient of variation (CV%) exceeds 40% for the originator product.
Please be advised, however, that the clinical protocol must be previously submitted to the technical evaluation of Therapeutic Equivalence Coordination (Anvisa) before conducting the bioequivalence study that you want to consider the scaling.”
Interesting. As usual the devil is in the details. IMHO, two interpretations are possible.
- Use EMA’s regulatory constant k 0.760 which is derived from the regulatory standard deviation σ0 based on the switching condition CVWR of 30%:
σ0 = √ln(0.302+1) = 0.2936
k = ln(1.25)/σ0 ≈ 0.760
Scale according to EMA’s formula [L, U] = ℯ±k·sWR but apply widening of the acceptance range only if CVWR >40%. This would lead to a discontinuity (similar to FDA’s “implied BE limits” based on a switching condition of ~25.4% [σ0 0.25] applied at ≥30%):
CVWR AR (%)
0.20 80.00 125.00
0.25 80.00 125.00
0.30 80.00 125.00
0.35 80.00 125.00
0.40 80.00 125.00
0.45 72.15 138.59
0.50 69.84 143.19
0.55 69.84 143.19
0.60 69.84 143.19
- If ANVISA wants 40% as the switching condition that would translate into σ0 0.3853 and k 0.579. No discontinuity but very little gain in terms of the acceptance range:
CVWR AR (%)
0.20 80.00 125.00
0.25 80.00 125.00
0.30 80.00 125.00
0.35 80.00 125.00
0.40 80.00 125.00
0.45 77.99 128.23
0.50 76.07 131.46
0.55 76.07 131.46
0.60 76.07 131.46
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
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Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- ANVISA’s home brewed scaling?Helmut 2015-05-28 18:27 [RSABE / ABEL]
- ANVISA’s home brewed scaling? ElMaestro 2015-05-28 19:10
- ANVISA: TIE, sample size Helmut 2015-06-02 16:00
- ANVISA: scABEL TIE d_labes 2015-06-03 11:59
- ANVISA: scABEL TIE Helmut 2015-06-03 12:07
- ANVISA: scABEL TIE part II d_labes 2015-06-03 13:19
- ANVISA: scABEL TIE part II nobody 2015-06-03 13:31
- ANVISA: scABEL TIE part II d_labes 2015-06-03 14:00
- ANVISA: scABEL TIE part II nobody 2015-06-03 13:31
- ANVISA scABEL - sample size d_labes 2015-06-05 11:03
- ANVISA: scABEL TIE part II d_labes 2015-06-03 13:19
- ANVISA: scABEL TIE Helmut 2015-06-03 12:07
- ANVISA: scABEL TIE d_labes 2015-06-03 11:59
- ANVISA: TIE, sample size Helmut 2015-06-02 16:00
- ANVISA’s home brewed scaling? Lucas 2015-06-02 16:02
- ANVISA’s home brewed scaling? Helmut 2015-06-02 16:16
- ANVISA’s home brewed scaling? ElMaestro 2015-05-28 19:10