Insulin may be more heat-stable during 28 days of use than current labeling suggests, a new study indicates.
Instructions on insulin vials or pens indicate that they be stored unopened at temperatures of 2° to 8° C (35.6° to 46.4° F). Once the seal is punctured and during 28 days of use, the label indicates that the insulin be stored at temperatures of 25° to 30° C (77° to 86° F).
But in many resource-poor settings, as well as in many parts of the developed world, ambient temperatures can be higher than that.
The study was conducted under laboratory conditions mimicking those of a refugee camp in northern Kenya, where temperatures typically fluctuate between 25° C (77° F) at night and 37° C (98.6° F) during the day.
During 28 days of exposure to the oscillating temperatures, as well as for up to 12 weeks, there were no differences in the physical structure (measured by liquid chromatography), bioactivity (via hepatocytes), or appearance of insulin in vials or cartridges compared to insulin stored at temperatures of 2° to 8° C (35.6° to 46.4° F). This was the case for both human insulin and analogue formulations.
The finding is important in regard to low-resource settings, where patients who don’t have refrigerators in their homes often have to travel to and from a hospital or clinic twice daily to receive their insulin doses.
“This shows it’s possible for the patient to treat themselves during the 4 weeks without having to put the insulin back in the fridge. If the temperature is oscillating, that’s not a problem,” senior author Leonardo Scapozza, PhD, professor of pharmaceutical biochemistry/chemistry at the University of Geneva, Geneva, Switzerland, told Medscape Medical News.
The results of the study by Béatrice Kaufmann, also of the University of Geneva, and colleagues were published online February 3 in PLOS ONE.
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People Will Now Be Able to Inject Themselves With Insulin at Home
The study was co-conducted with the humanitarian organization Doctors Without Borders / Médecins Sans Frontières (MSF).
“For far too long, we were unable to send people with diabetes back to their homes with insulin due to its cold storage requirements. Some of these people were traveling long distances daily, and some even relocated to get their insulin injections at the clinic,” MSF noted in a statement.
“With this new finding of no refrigeration requirement in a climate of up to nearly 99° F — and with a well-developed patient education and support program — people with diabetes in resource-limited and humanitarian settings will now be able to inject themselves in their homes,” the organization said.
“This greatly improves the significant disruption to their lives…. The ability to self-inject insulin is a fundamental aspect of diabetes self-management and the ability of people with diabetes to be empowered,” the statement continued.
Findings Also Relevant for Developed World
These findings are also relevant in the developed world in situations ranging from natural disasters to insulin vials inadvertently being left for hours in a hot car.
“If you add energy, insulin will go toward unfolding and precipitation, but there is a point of return where if you cool it down again, it is still reversible to normal conformation. With oscillating, you don’t add sufficient energy to get to the point of no return,” Scapozza explained.
On the other hand, with continuous exposure to a temperature of 31° C (87.8° F), all insulin formulations began to degrade and showed diminished bioactivity after 4 weeks. Two of the insulin formulations began to degrade after 1 week of continuous exposure to 37° C (98.6° F).
This finding reinforces current recommendations that the insulin in insulin pumps ― in which insulin is typically exposed continuously to body temperature ― should be replaced every 3 days, he noted.
Importantly, when the insulin did degrade, particles appeared in the vial. “When insulin shouldn’t be used anymore because it’s degraded more than 5% of the [Pharmacopeia] limit, then the patient will see the insulin falling out as precipitation. This is a very important message,” he said.
“Just look, and if you see particles in bottle, at that point the insulin is bad and shouldn’t be used…. Within the 28 days, as long as it looks okay, it’s okay,” Scapozza emphasized.
The authors stress that prior to the 28-day period of use, insulin should be kept strictly at the recommended temperature of 4° C (39.2° F); they emphasize the importance of maintaining the cold chain.
Insulin up to 12 Weeks; Freezing It Does Most Damage
However, they did find that insulin remained stable for longer than 28 days ― in fact, for up to 12 weeks. Those data will be reported in a subsequent article.
This finding may also be relevant in both the developing and developed worlds, such as in a situation in which a person is traveling with backup insulin vials without refrigeration capability.
Thus far, the data seem to suggest that “if you use one vial every 28 days, you can have three vials with you without any problem. If you have five vials and stay 12 weeks, then most likely the unused insulin can’t be used anymore…but you can see it [if the insulin degrades],” Scapozza said.
Ideally, some key questions should be answered before these data can be incorporated into the insulin labeling, he noted.
“What about 23° to 40° C? What about 25° to 27° C, but night being shorter, so 18 hours day and only 6 hours night? These are questions we’ve been asking, and results are encouraging,” he said.
Scapozza mentioned something else to Medscape Medical News that wasn’t in the article.
“What is the worst thing for insulin? Freezing. If you freeze insulin, the activity is gone within 1 day. Insulin is much more sensitive to freezing than heat. When you freeze, ice crystals form from water. They’re very sharp and really destroy the structure of proteins.”
The research was funded by MSF Switzerland. The authors have disclosed no relevant financial relationships.
PLoS One. Published online February 3, 2021. Full text