Preventing loss of activity or aggregation during storage and shipping is essential to maintain the safety and efficacy of biopharmaceutical products. Proteins are inherently sensitive to environmental stresses such as temperature fluctuations, agitation, light exposure, and freeze–thaw cycles encountered throughout the supply chain. This topic examines the mechanisms that drive degradation and aggregation during long-term storage and distribution, and how formulation composition, container–closure systems, and handling conditions influence product stability. It highlights strategies for designing robust formulations, defining appropriate storage conditions, and implementing effective shipping controls to preserve bioactivity, ensure shelf-life claims, and meet regulatory and patient expectations.