Acceptance Limits for the New ICH USP 29 Content-Uniformity Test - Pharmaceutical Technology

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Acceptance Limits for the New ICH USP 29 Content-Uniformity Test
Revisions to the United States Pharmacopeia's (USP) uniformity test require manufacturers to establish new acceptance limits. The authors present their method for calculating acceptance limits consistent with USP's revised content-uniformity test requirements.

Pharmaceutical Technology

Using the inequality that, for two events A and B:

P(A and B) = P(A) + P(B) – P(A or B) ≥ P(A) + P(B) – 1

It follows that:

P(S 2) = P(C 21 and C 22) ≥ max {P(C 21) + P(C 22) – 1, 0}

Since criterion C 21 is similar to S 1 except for n = 30 and k = 2.0 in the former while n = 10 and k = 2.4 in the latter, the calculation of P(C 21) is carried out similarly as in P(S 1) with n = 30 and k = 2.0. Therefore:

Therefore, a lower bound on the probability of passing USP requirements is max {P(S 1), P(S 2)}.

Figure 1. 95% lower bound on passing the USP test for dose uniformity (target 5 100%).
For a given value of μ and a given value of σ, a lower bound (LBOUND) can be determined using the above calculations. Figure 1 shows a contour for the combinations of μ and σ that have an LBOUND of 95% assuming a target, T, of 100. Any combination of μ and σ at or below the contour results represents at least a 95% chance of samples passing the USP content uniformity test.

The "true" probability of passing the USP test can be found by simulation. Table I gives a comparison of the simulated probabilities and the LBOUND calculation.

Table I: Simulated (SIM) versus lower bound (LB) probabilities of passing content-uniformity test.
As can be seen in Table I, the LBOUND calculations are fairly close to the simulated results across various population means and standard deviations.


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