Vol. 7, Issue 2, Part G (2025)

The integrity of pharmaceutical products hinges on rigorous stability assessment, a process standardized by the International Council for Harmonisation (ICH) guidelines to account for global climatic variability. ICH Q1A(R2) categorizes climates into Zones I–IVa/b, each with distinct temperature and humidity profiles that dictate storage conditions, testing durations, and shelf-life projections. This comprehensive review delves into the regulatory evolution of these zones, their physicochemical implications on drug degradation pathways, and their direct bearing on shelf-life determination for diverse dosage forms. We examine zone-specific challenges, such as hydrolytic risks in humid tropics (Zone IVb) versus oxidative threats in temperate areas (Zone I), supported by empirical data from stability studies. Comparative analyses highlight extrapolation limits, bracketing strategies, and post-approval variations. Integrating recent advancements like predictive modeling and real-world evidence, this article advocates for adaptive, zone-tailored protocols to bolster global harmonization and mitigate supply chain vulnerabilities. With climate change exacerbating zonal shifts, proactive formulation design emerges as pivotal for ensuring therapeutic reliability.