Comprehensive Temperature Excursion Management Program for the Commercial Distribution of Biopharmaceutical Drug Products

Abstract

Biopharmaceutical drug products may be exposed to temperatures outside of the intended storage temperature range (typically 2-8°C) during commercial distribution due to uncontrolled variables and unexpected events. Pharmaceutical companies are expected to ensure that product quality and stability are not negatively impacted by temperature excursions defined as being acceptable for the product. It is imperative that all firms involved in the distribution understand key elements of the temperature excursion management program in place to overcome the challenges of global distribution and comply with regulatory requirements. Proactive implementation of a comprehensive temperature excursion management program is expected to help achieve successful commercial distribution. In this article, important aspects related to the key elements of a comprehensive temperature excursion management program are summarized, including standard stability testing, regulatory expectations related to the justification of temperature excursions, thermal cycling studies to assess and support potential temperature excursions (including how/when thermal cycling study data is used to support temperature excursions), good distribution practices to minimize temperature excursions and use of theoretical methods/mathematical simulation models to assess temperature excursions. A comprehensive temperature excursion management program is expected to ensure product quality and help minimize, assess, and justify temperature excursions more efficiently, ensure regulatory compliance and avoid business impact caused by the loss of products or inadequate supply.

Keywords: Biopharmaceutical drug product; Commercial distribution; Good distribution practices; Mean kinetic temperature; Regulatory expectations; Stability testing; Temperature excursion; Thermal cycling; mAb.