The impact of dry ice exposure on pH change during biologics transport and mitigation strategies

Abstract

Cold chain with dry ice is extensively used in the pharmaceutical transportation. Containers designed for cryo-storage are often placed contact with CO₂ released from dry ice, yet the effects of CO₂ on drug formulations during pharmaceutical transportation are infrequently discussed. In this study, the impact of pH change on various containers and buffer systems, the ingress pathway of CO₂ and the mitigation control strategies were investigated. The findings revealed notable pH changes in various types of containers with 5 mL polycarbonate bottles, 150 mL Corning bottles, and plastic tubes, while glass vials with stopper and capping maintained better pH stability. Buffer systems with a higher initial pH, such as phosphate and Tris buffers, were more prone to disturbances. Additionally, buffers with higher ionic strength showed an enhanced capacity to counteract pH reductions. The probability of CO₂ ingress pathway largely depends on the integrity of the sealing approaches at low temperature. Control strategy involving temporary uncapping during thawing and the use of secondary packaging sealed with an aluminum foil bag during transportation proved effective. This research expounded the impact of dry ice on pH change and strategic control measures within pharmaceutical supply chains, aiming to improve understanding of the variables related to container use in scenarios involving dry ice transportation.