Insulin Storage: A Critical Reappraisal

Abstract

Insulin, as a peptide hormone drug, is susceptible to changes in stability when exposed to environmental factors under storage. Proper storage according to the manufacturer’s recommendations is important to maintain its potency and enable precise dosing for people with diabetes (PwD). While it is reasonable to assume that transport conditions and temperature are well controlled during the supply chain, little is known about insulin storage after dispensing and insulin potency at the moment of administration. Insulin is exposed to various environmental factors when carried by PwD and storage recommendations are often not met when it is stored in household refrigerators. It is difficult to assess changes in insulin potency in clinical practice, and there is a gap in the current scientific literature on insulin stability. Package leaflet recommendations only give limited information on the impact of improper storage conditions on insulin stability and guidelines by health organizations are inconsistent. Given the importance of precise dosing in diabetes care, there is a need for more transparency on insulin stability, awareness for proper storage among health care professionals and PwD as well as clear guidelines and practical storage recommendations from manufacturers and health organizations.

Quality Assurance of Commercial Insulin Formulations: Novel Assay Using Infrared Spectroscopy

“…It is clear that the biological potency depends on the structure of the protein 27 and degradation is seen even for misfolded monomers as the first step, after which aggregation and fibrillation occur. The awareness for shelf lifetime reduction, as induced by insulin stability impairment from inappropriate storage conditions of insulin formulations after product release from the manufacturer until usage by people with diabetes, has been brought into focus in a recent critical review from Heinemann et al 28 The new USP general chapter 1049.1 is recommending requirements for stability studies, especially having an appropriate study design for biopharmaceutical products. 29…”

FT-IR versus EC-QCL spectroscopy for biopharmaceutical quality assessment with focus on insulin—total protein assay and secondary structure analysis using attenuated total reflection

“…All insulin samples were stored in their original vials at recommended temperatures around 5°C using a refrigerator [1]. The USP human insulin standard was dissolved in a standard phosphate buffer at pH = 7.4 according to Sörensen and stored in sealed plastic tubes, guaranteeing highest sterility.…”

“…There are different challenges for the quantification and determination of the molecular stability in pharmaceuticals during production or later when obtained from pharmaciesespecially after long-term storage under different environmental conditions that may be limiting their lifecycle. These adverse storage conditions can be associated with breaking the storage cold chain or during transport, encountered with shaking and elevated temperatures [1]. First deteriorating effects can be protein misfolding with drastic changes in the protein secondary structure, followed by protein aggregation and fibril forming leading to a reduction in the potency of the active pharmaceutical ingredient [2][3][4].…”

Microneedle-based insulin transdermal delivery system: current status and translation challenges

“…Sometimes it is difficult to achieve the ideal and precise dose and as a result, hyperglycemia and hypoglycemia often occur. Moreover, as a biological peptide, insulin has poor stability and needs to be kept between 2 and 8 °C during distribution and shelf life storage [ 7 ], which increases the difficulties of transportation and storage in some developing countries. Therefore, it has become the focus of insulin drug product development to achieve more stable, convenient, painless, long-acting, and glucose-monitoring insulin preparation.…”