Temperature Excursion Management: A Tier-Based Approach for Commercial Oral Solid Dosage Forms.

Abstract

Temperature excursions during product storage, transportation, and handling can deteriorate product quality. Following a temperature excursion event, the impact of the event on the product quality should be evaluated to determine if the product can be used or if it needs to be discarded. Pharmaceutical companies are required to have defined procedures for managing temperature excursions and performing impact assessment after an excursion occurs. In an increasingly complex supply chain, it is vital to develop processes that can expedite the review of these events. A tier-based approach is presented for analyzing the impact of temperature excursion on commercial small molecule drug products intended to be stored at room temperature. Utilization of each of the three tiers is based on whether the excursion temperature and/or excursion duration are within a predetermined, product-specific, allowable range. The stress study temperature defines the allowable temperature range, while the allowable duration is determined using a mathematical approach outlined in this article. Tier 1, specific to the product, allows products to be dispositioned for use without further assessment when temperature excursion events fall within both the product-specific allowable excursion temperature and duration ranges. Tier 2 applies when the excursion temperature is within the allowable range, but the duration exceeds it. Lot-specific release data is used for impact assessment in this tier. Finally, Tier 3 utilizes Arrhenius extrapolation to predict the final degradation and perform the impact assessment when the excursion temperature surpasses the allowable temperature range.