T/R potency <5% [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2022-09-09 19:08 (616 d 14:28 ago) – Posting: # 23286
Views: 2,464

Hi Achievwin,

❝ It is not about potency correction, it is about controlling errors wherever possible …


Agree.

❝ I believe I heard (in the 2000 BE workshop) rationale for this 5% difference is to accomodate aging differences (time of manufacture to time of dosing) between Test and RLD (usually RLD is older than Test …


Which workshop? Let’s compile what we have:

❝ … and also assay variabilities (Damn: everyone blames poor analytical chemist :confused::confused:).


That’s the point. What are the batch release spec’s? Generally ±10% and for NTIDs ±5%. Of course, you don’t get a CoA from the originator. Analyzing the reference with the method validated for the test is not a problem for IR. Little bit more tricky for MR. A nightmare for creams and ointments with their fantastic emulsifiers. You never can’t be sure. Yes, analytical (in)accuracy and (im)precision hits … Say, you have a great routine method with 2% and you measure a potency 100% for T and R. What are the true values? Can be <100% for T and >100% for R. That’s why in sample size estimation one should never (ever!) assume a T/R-ratio of 1.

In [image]:

set.seed(20220909)
T <- rnorm(n = 1e7, mean = 1, sd = 0.02)
R <- rnorm(n = 1e7, mean = 1, sd = 0.02)
round(quantile(T / R, probs = c(0.025, 0.5, 0.975)), 4)
 2.5%   50% 97.5%
0.946 1.000 1.057

That’s why in most sample size functions of PowerTOST 0.95 is the default.

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