What is the stability and sterility data for regular insulin stored in polypropylene syringes under refrigeration?

What is the stability and sterility data for regular insulin stored in polypropylene syringes under refrigeration?

Comment by InpharmD Researcher

Overall, stability data for regular insulin stored in syringes is sparse. Two studies have observed stability in polypropylene syringes for up to 28 days (Tables 1 and 2). Additional studies investigate stability of insulin mixed with 0.9% NaCl solution in polyvinyl chloride and polypropylene bags, demonstrating stability for 24 hours to 14 days.

Intravenous infusion bags prepared with HUMULIN R may be stored for 48 hours when refrigerated at 36° to 46°F [2° to 8°C]. The prepared intravenous infusion bags may then be stored at room temperature for up to an additional 48 hours.

Background

A 2022 study investigated the physicochemical stability of ready-to-administer human insulin 1 IU/mL injection solution from two different brands (Huminsulin® and Actrapid Penfill®) when stored in disposable 50 mL plastic syringes. The products were diluted with 0.9% NaCl, prepared in polypropylene syringes (PVC and latex-free), and stored for 90 days at 2-8°C dark room or 20-25°C diffused light room. The results found that the concentration was stable (> 90%) after 90 days in the 2-8°C group, but was stable for at least 14 days in the 20-25°C group. [1]

Relevant Prescribing Information

Unopened HUMULIN R vials may be stored for up to 31 days at room temperature or until expiration under refrigeration. Opened HUMULIN R vials may be stored for 31 days at both room temperature and under refrigeration.[2]

Diluted HUMULIN R for subcutaneous injection may be stored for 28 days when refrigerated at 36° to 46°F [2° to 8°C] or for 14 days at room temperature up to 86°F (30°C).

Intravenous infusion bags prepared with HUMULIN R may be stored for 48 hours when refrigerated at 36° to 46°F [2° to 8°C]. The prepared intravenous infusion bags may then be stored at room temperature for up to an additional 48 hours.

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What is the stability and sterility data for regular insulin stored in polypropylene syringes under refrigeration?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Table 1 for your response.

Stability of U-500 regular insulin in prefilled syringes
Design	Stability study
Objective	To determine if U-500 insulin is stable when stored in prefilled syringes at 4°C for up to 28 days
Methods	Insulin U-500 (Humulin R) was drawn up into 1 mL polypropylene syringes in a clean, nonsterile environment to emulate the conditions of a patient’s home. In each syringe, 0.25 mL (125 U) were drawn up; a total of 15 samples were created. The samples were stored under refrigeration (3-5°C). At time point 0 (baseline) and after 7, 14, 21, and 28, three of the stored syringes were removed for high-performance liquid chromatography (HPLC) analysis.
Duration	Up to 28 days
Results		Percent of initial concentration remaining
	Day 7	97.848 ± 0.629%
	Day 14	99.432 ± 3.857%
	Day 21	99.906 ± 2.389%
	Day 28	93.317 ± 2.379%
	The drop in percentage remaining (7%) was not considered statistically significant.
Study Author Conclusions	U-500 insulin in prefilled syringes stored at 4°C is stable for up to 28 days. Prefilled syringes containing U-500 insulin and stored at 4°C for up to 28 days can be used confidently by caregivers for treating patients with diabetes with severe insulin resistance who are unable to independently manage a traditional vial and syringe.[1]
InpharmD Researcher Critique	While the methodology of this study was sound, the individual values were not reported. The prescribing information for U-500 insulin states that it must be used within 31 days of initial use or otherwise should be discarded. This should be taken into consideration when preparing prefilled syringes of U-500 insulin for subsequent storage.

References:
[1] [1] Lull ME, Piacentino JJ, Traina AN. Stability of U-500 regular insulin in prefilled syringes. J Am Pharm Assoc (2003). 2013;53(3):304-306. doi:10.1331/JAPhA.2013.12164