Establishing Content Uniformity Criteria throughout 3-Stage Validation: Estimate, Confirm, and Control

Two recent events have prompted the development of establishing content uniformity throughout a 3-stage process validation.  The first was the withdrawal of the "Powder Blends and Finished Dosage Units - Stratified In-Process Dosage Unit Sampling and Assessment".  The second was the re-emphasis that the Uniformity of Dosage Units (USU) / USP <905> is intended to be applied to product on the market, not as a release test.  The goal is to guard against %RSD of 7.5%.  During process validation Stage 1 and 2, an increased sample size is recommended to more accurately determine the process mean and standard deviation.  The Stage 3 process validation will use the appropriate sample size based on the true estimate of the standard deviation from the larger sample size in Stage 2.  Statistically based sampling plans and acceptance criteria is then developed for release to assure quality product on the market meets the USP <905>.  This 3-Stage approach provides a path to estimate, confirm and control the product quality.