<905> applies to each drug substance in the product. <905> procedures can be applied to each substance individually so if one or more meet the conditions summarized in Table 1, it can be tested using the Weight variation procedure.
The limit for the Acceptance Value is 15.0% at both levels of the test. L2 is only used to determine the acceptable range of individual values observed when 30 units have been analyzed. Where the average result is more than 101.5% then M has the value of 101.5% and the range is calculated as in the question.
Section 5.70 of the General Notices says that when the same analytical methodology is used for the Assay and the Content uniformity with appropriate allowances made for differences in sample preparation, the average of all the individual-unit content uniformity determinations may be used as the Assay value.
The average weight of the units being tested by the Weight variation procedure is used in determining their estimated content.
The Assay is a separate test from <905>. It uses the analysis of a composite from multiple units. <905> evaluates uniformity of dose with the limit on the Acceptance Value and an acceptable range of individual values if testing proceeds to 30 units. In neither of these tests is there a requirement that individual results conform to the Assay limits, typically 90% to 110% of label claim.
The Weight variation procedure may be used to estimate the contents of the individual units under a few defined conditions. The results of a single procedure, Content uniformity or Weight variation, is sufficient to satisfy the test requirement in the chapter.
As a result of harmonization, the separate procedures and criteria for transdermal systems, suppositories and inhalations in pre-metered dosage units were removed from the chapter. These dosage forms are now classified as Others and require the use of the Content uniformity procedure. This is the same for any dosage form not meeting the conditions for the application of the Weight variation procedure.
<905> is not applied to liquids in multiple dose containers.
The value of T is used to modify the upper value of M. T represents a manufacturing target that is more than 100% (see General Notices, Section 4.10.20 Acceptance Criteria). Where the average value of the results is more than T, the Acceptance Value is calculated based on the absolute value of the difference (plus ks). Examples where T has the value of 107.5%, 10 units have been tested and SD is 3 are given in the following table.
|Mean||T||Is mean within 98.5% and T||Reference Value||Abs Value of the Difference (mean and reference value)||ks||AV|
The values observed from individual units tested by the Content uniformity procedure are in terms of the label claim. Outside of being part of the analysis of the drug substance content, the mass of the units are not considered.
The uniformity of dosage units can be demonstrated by either of the two methods. The Content uniformity procedure may be used in all cases. The Weight variation procedure can be used where permitted as detailed in Table 1. The Weight variation procedure may be used for products for which it is permitted.