Update of USP Chapter <1099> on Content Uniformity in Large Samples

In the current Pharmacopeial Forum, PF 51(3), the USP has published a revised draft of General Chapter <1099> Limit on Number of Large Deviations When Assessing Content Uniformity in Large Samples.

The briefing notes state the following: "This proposal is based on the version of the chapter official as of March 1, 2019. On the basis of comments received, the proposal published in PF 47(4) [Jul. –Sep. 2021] has been canceled and is being replaced with this new proposal. It seeks to clarify that <1099> is not linked to Uniformity of Dosage Units <905>. It also includes new Table 2 and moves the statistical formulas to an Appendix."

The draft provides a statistical method to assess large data sets using a zero-tolerance criterion (ZTC). New procedures and tables are introduced, allowing manufacturers to evaluate whether a large sample complies with target limits on deviations, especially when sample sizes exceed 30 units. The revised version introduces a flexible approach based on confidence intervals, particularly using Jeffreys’ method, to determine acceptable levels of variation.

The new draft can be viewed on the Pharmacopeial Forum website. The comment period is open until 31 July 2025.