Determination of Shelf-Life from Stability Data: From Replicates or from Averages?

A statistical analysis for determining an expiration date can be applied to replicates or their corresponding averages as suggested in industry guidelines. Stability data of samples of pharmaceuticals are often generated as replicate test results, typically as duplicates. A statistical analysis for determination of an expiration date can then be applied on either the replicates or their corresponding averages in line with the methodology suggested in International Council for Harmonisation (ICH) Q1A(R2) and Q1E guides. This paper aims at clarifying when a shelf-life derived from all replicates or averages is justified and correct. When replicate stability data represent preparations of the same sample, this is a case of pseudo-replication, and, therefore, the statistically derived shelf-life should be based on the averages of the replicates. However, when these replicate data represent independently and randomly selected and tested samples at each time point, a statistically derived shelf-life based on all replicate data is justifiable.