J Biopharm Stat. 2025 Mar 13:1-6. doi: 10.1080/10543406.2025.2473612. Online ahead of print.
ABSTRACT
Conventionally, the product quality specification and control chart limits are determined as the mean plus and minus 3 sample standard deviations with the assumption that the quality data is normally distributed. These limits correspond to an interval centered at the mean, covering approximately 97.3% of the population. The estimate of such an interval is called the β-content tolerance interval. It has been proposed to use a two one-sided β-content tolerance interval approach for determining drug product quality specifications. For a given confidence level, 1–α, and a coverage percentage p, the β-content tolerance interval is not precise when the sample size is small. For the derivation of a precise β-content tolerance interval, Faulkenberry and Daly proposed a “goodness” criterion for sample size determination. In order to avoid overestimating the β-content tolerance interval when p is large, we propose to define the precision requirement as the probability of the tolerance interval covering more than 1+p2 is restricted to a pre-specified significance level α‘. Quality specification studies are often not planned with proper sample sizes. To obtain precise β-content tolerance intervals for quality specification studies, the proper coverage p satisfying the “goodness” criterion and the minimum sample sizes were also determined with the pre-specified significance level α‘. With this approach, one may properly set the product specificationwhile avoiding over-specifying the quality limits.
PMID:40079049 | DOI:10.1080/10543406.2025.2473612
