Insulin | WHO | Diabetes
Thermostability of Human Insulin
Understanding the Stability and Storage Challenges of Human Insulin in Varied Environmental Conditions
Background
Diabetes is an escalating global health crisis, expected to impact 1.3 billion people by 2050.
Among the global diabetic population, approximately 9 million people live with type 1 diabetes and require insulin, while around 60 million people with type 2 diabetes need insulin to achieve optimal glycemic control. However, only about 50% of these individuals have access to this essential medication.
The availability of human insulin is often limited, particularly in healthcare systems where patients cannot afford more expensive insulin analogues. This scarcity has led to significant constraints on ensuring universal access to insulin, even in high-income countries where self-rationing of insulin among diabetics has been reported to reduce costs, resulting in severe health consequences.
WHO Global Diabetes Compact
The introduction of higher-priced insulin analogs since the 2000s has shifted the insulin market, making human insulin less in demand and thus more expensive. This shift has further disrupted the global supply of human insulin, limiting its availability and making it less affordable.
To address the growing burden of diabetes, WHO launched the Global Diabetes Compact with a goal to reduce diabetes risk and ensure equitable, comprehensive, affordable, and quality treatment for all diagnosed individuals. One of the six workstreams focuses on increasing access to essential diabetes medicines, including insulin.
Thermostability of Human Insulin
The stability of human insulin is influenced by various environmental factors such as purity, pH, humidity, structural changes in the insulin molecule, and substances added to enhance absorption. Insulin is particularly susceptible to high or low ambient temperatures, sunlight, and prolonged usage beyond the expiration date. High temperatures can cause irreversible conformational changes and formation of insulin fibrils, leading to denaturation. Fluctuating temperatures may not cause irreversible aggregation compared to continuous heating, but insulin must still be protected from heat and freezing conditions.
Regulatory authorities emphasize the temperature sensitivity of human insulin, advising storage at low temperatures (2°C to 8°C) with reliable refrigeration. Once opened, insulin can be stored at ambient temperature and used for four to six weeks. However, in LMICs with warm climates and limited refrigeration access, insulin exposure to extreme heat is common. This underscores the need for a nuanced understanding of insulin’s thermostability.
Clinical and Non-Clinical Data on Insulin Thermostability
A systematic Cochrane review examined published studies and unpublished data from insulin manufacturers. The review found no substantial loss of insulin activity under various storage conditions and temperatures, with data indicating that insulin retained its potency for up to six months at 25°C and two months at 37°C. However, data on bacterial endotoxins, sterility, and insulin pumps were unavailable.
Conclusion
Optimal cold-chain management of human insulin is essential from manufacturing to delivery. In LMICs with limited refrigeration access, integrated supply chain approaches could improve efficiency and reduce spoilage. Stability studies considering LMIC settings are key to enhancing the availability and affordability of human insulin. Manufacturers should continue researching insulin stability to provide updated storage guidance, ensuring that life-saving medicines remain accessible in challenging environments.
