Scientific rationale for sampling regimen and acceptance criteria of blend uniformity based on Monte Carlo simulation

This study proposes an alternative sampling regimen (number of sampling points, number of samples from each sampling point) and setting of the acceptance criteria for blend uniformity based on a statistical rationale. Currently, the sampling regimen and the acceptance criteria for the blend uniformity test of powder blends are determined according to the withdrawn guidance for industry by the Food and Drug Administration (FDA) and the proposal of the International Society for Pharmaceutical Engineering (ISPE)-sponsored Blend Uniformity and Content Uniformity (BUCU) Group to substitute the withdrawn guidance. However, both approaches lack scientific rationale in their publications. Herein this study addresses the scientific background based on the simulations utilizing the Monte Carlo method, in order to provide a scientific rationale for the sampling regimen and acceptance criteria. False positive probability, defined as the probability of failure to meet the minimum necessary requirement in future samples even when the tested sample satisfies the acceptance criteria in fact were used to evaluate the adequacy of the sampling regimen and acceptance criteria. This study aims at stimulating the discussion about blend uniformity that may ensure a higher quality of pharmaceutical products finally.