Establishing Target Fills for Semisolid and Liquid Dosage Forms

April 1, 2005

To meet the requirements of the USP ?755? Minimum Fill and ?698? Deliverable Volume tests, target fill levels greater than 100% must be established. This article proposes a criterion for establishing an appropriate target fill level such that a sample will have a 95% probability of passing these USP tests at 95% confidence.

Meeting the USP requirements for minimum fill and deliverable volume is a serious concern in pharmaceutical production. Filling operations must be controlled throughout the filling cycle to ensure that the sampled filled products will meet quality control specifications based on the USP ‹755› Minimum Fill or ‹698› Deliverable Volume tests. The common acceptance criterion of the two USP tests is that the average content of all samples tested must not be less than 100% of the labeled amount. Such a requirement will lead to a filling volume target greater than 100% of the labeled amount. This article proposes a criterion for establishing an appropriate target fill such that a sample will have a 95% probability of passing these USP tests at 95% confidence, i.e., that the established target fill will guarantee with 95% confidence that 95 out of 100 samples will pass the USP tests.

The USP ‹755› Minimum Fill test

The

USP

‹755› Minimum Fill test applies to liquids, semisolids, and solids such as creams, gels, jellies, lotions, ointments, pastes, powders, and aerosols, including pressurized and nonpressurized topical sprays that are packaged in containers in which the labeled amount is not more than 150 g or 150 mL (1).

Figure 1: Operating characteristic curves for a USP Minimum Fill sampling plan (