Significance and Use
4.1 The methodology was originally developed (1-4)6 for use in drug content uniformity and dissolution but has general application to any multistage test with multiple acceptance criteria. Practice E2709 summarizes the statistical aspects of this methodology. This practice applies the general methodology of Practice E2709 specifically to the UDU test.
4.1.1 While other methods can be used to estimate the probability of passing the UDU test, they are outside the scope of this practice.
4.2 The UDU test procedure describes a two-stage sampling test, where at each stage one can pass or continue testing, and the decision to fail is deferred until the second stage. At each stage there are acceptance criteria on the test results as outlined in Table 1.
4.3 The UDU test is a market standard. The USP General Notices include the following statement about compendial standards. “The similarity to statistical procedures may seem to suggest an intent to make inference to some larger group of units, but in all cases, statements about whether the compendial standard is met apply only to the units tested.” Therefore, the UDU procedure is not intended for inspecting uniformity of finished product for lot/batch release or as a lot inspection procedure.
4.3.1 The UDU test defines a product requirement to be met at release and throughout the shelf-life of the product.
4.3.2 Passing the UDU test once does not provide statistical assurance that a batch of drug product meets specified statistical quality control criteria.
4.4 This practice provides a practical specification that may be applied when uniformity of dosage units is required. An acceptance region for the mean and standard deviation of a set of test results from the lot is defined such that, at a prescribed confidence level, the probability that a future sample from the lot will pass the UDU test is greater than or equal to a prespecified lower probability bound. Having test results fall in the acceptance region provides assurance that a sample would pass the UDU test with at least the specified lower bound probability. This procedure does not account for any decrease in potency during the shelf life, which could affect the ability to meet the UDU test requirements.
4.5 This practice can be used as an element for process demonstration or validation, continuous process verification, in-process testing, or lot release (acceptance). As the circumstances and available information vary in these different application areas, this practice does not prescribe a specific target, sample size, lower probability bound, or confidence level. These must be prospectively selected by the user and may be different from those used in the acceptance limit tables provided in this practice.
Scope
1.1 This practice provides a general procedure for evaluating the capability to comply with the Uniformity of Dosage Units (UDU) test. This test is given in General Chapter <905> Uniformity of Dosage Units of the USP, in 2.9.40 Uniformity of Dosage Units of the Ph. Eur., and in 6.02 Uniformity of Dosage Units of the JP, and these versions are virtually interchangeable. For this multiple-stage test, the procedure computes a lower bound on the probability of passing the UDU test, based on statistical estimates made at a prescribed confidence level from a sample of dosage units.
1.2 This methodology can be used to generate an acceptance limit table, which defines a set of sample means and standard deviations that assures passing the UDU test for a prescribed lower probability bound, confidence level, and sample size.
1.3 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.
1.4 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
