Cold Chain Resilience Across Humanitarian and Resource-Constrained Settings: A Hybrid Simulation Framework

Cold chain systems are vital for preserving vaccines and other temperature-sensitive medicines, but in fragile, resource-constrained, and crisis-affected settings, they remain highly vulnerable to power instability, damaged infrastructure, and extreme climates. Existing modeling approaches commonly capture supply flows but overlook the interaction of thermal, logistical, and behavioral stressors that influence real-world resilience. This study introduces a hybrid simulation framework that integrates physics-based refrigeration dynamics, power variability, logistics processes, agent behavior, stochastic disruptions, and temperature-dependent spoilage evaluation. The framework was applied to four illustrative contexts: Gaza conflict-affected setting, Sudan rural conflict-affected setting, Nepal highlands setting, and Haiti post-earthquake setting. Results reproduced realistic vulnerability patterns. Clinics consistently emerged as the weakest nodes, with larger temperature fluctuations and frequent downtime, while depots and warehouses maintained relative stability. Power instability was the dominant driver of thermal risk across all settings, overshadowing transport or behavioral factors. Interventions that improved grid stability or overall infrastructure reduced temperature excursions and downtime by up to 60%, whereas isolated equipment upgrades frequently had minimal or negative effects due to higher power consumption. The results showed that cold chain resilience emerged from the interaction of environmental, infrastructural, and behavioral factors rather than equipment performance alone. The framework provides a flexible tool for stress-testing interventions and supports evidence-based and context-specific strategies to safeguard equitable access to essential medicines in vulnerable settings.