All Times EDT
Keywords: shelf-life determination, tolerance interval, ANCOVA
Shelf life of a drug product is determined conventionally based on up to 24 months (usually between 12 to 24 months) observed values for critical quality attributes from available batches prior to the regulatory approval of a new drug application. The data consists of three biobatches and is analyzed with the statistical method recommended in ICH Q1E. During the last 30 years, many statistical publications proposed a variety of approaches on the topic of shelf life determination especially when the number of batches used is larger than 3. In this poster, we compare two approaches of shelf life determination using various number of batches. One approach is the ANCOVA method by which the shelf life is determined by the worst batch if batches can’t be pooled and is otherwise determined by the pooled data of all batches. The other approach is based on the tolerance interval of a linear mixed model. The shelf life is determined by the lower confidence limit of the 5th percentile of shelf lives of all batches. We compare these two approaches using simulated data sets of 3, 6, 20 and 40 batches. Our simulation results show that the ICH method is rather conservative. When the number of batches increases, the batches are less likely to be pooled, which yields the underestimation of shelf life. The estimated shelf life using tolerance interval approach may alleviate such underestimation when the number of batches is large.