Drug Shelf Life and Release Limits Estimation Based on Manufacturing Process Capability

Specification limits are the competence regulatory agencies, whereas the release limit is a manufacturer's internal specification to be applied at the time of batch release to assure that quality attributes will remain within the specification limits until the expiry time. The aim of this work is to propose a method to set the shelf life from drug manufacture process capacity and degradation rate, using a modified version of the proposed method by Allen et al. (1991) Two different data sets were used to do this. The first data set corresponds to analytical method validation to measure the insulin concentration in order to estimate the specification limits, whereas the latter set gathered information on stability data of six batches of human insulin pharmaceutical preparation. In this context, the six batches were divided into two groups: Group 1 (batches 1, 2, and 4) was used to estimate shelf life; Group 2 (batches 3, 5, and 6) was used to test the estimated lower release limit (LRL). The ASTM E2709-12 approach was applied to verify that the future batches fulfill the release criterium. The procedure has been implemented in R-code.