In practice, current technology typically returns sample sizes of a few hundred, so that if the first largely deviating unit
is allowed at n = 500, it was argued by several stakeholders that such acceptance criteria would not fully resolve the main
concern—the 2.9.40 zero-tolerance criteria for a largely deviating unit.
Table II: Adopted test (Ph.Eur. supplement 7.7): Number of largely deviating units allowed for a selection of sample sizes.
|
On the other hand, a batch that complies with the adopted acceptance criteria for LDU when evaluated on a large sample would
have a 75% probability to pass the zero-tolerance criterion for LDU when evaluated on a small sample n = 30 (9). An extract
of the revised acceptance criteria that are now integrated in the adopted chapter 2.9.47 is presented in
Table II
:
"Editorial issues." In the adopted Ph. Eur. text, the introduction to the general chapter has been rewritten to further clarify the relationship between the two alternative
tests of 2.9.47 and the existing 2.9.40 (as discussed above). The tables of acceptance criteria (k, c1, c2 versus sample size
n) have been expanded, and there has been no rounding of the sample sizes performed where a certain set of acceptance criteria
apply.
The criteria for a "medium-sized" batch sizes (30 < n < 100) have been removed, as these were found to be less relevant
for the problem statement (demonstration of UDU using large sample sizes).
Demonstration of the performance of the adopted 2.9.47 test. In the following, a series of operations characteristic (OC)
curves are presented to demonstrate the performance of the new test, compared with the performance of the harmonised UDU test
(Note: in the figures, Alternative 1 and 2 are denoted as "Option 1 and 2"; reference is also made to
Figure 2
).
Figure 3: OC curves for normal distributed batches with an off-target mean.
|
Figure 3
represents the same situation as shown in
Figure 2,
except that the simulated batches has an off-target mean at 96 %. The batches are normal distributed around the off-target
mean.
|
