STABILITY AND STERILITY OF BIOSYNTHETIC HUMAN INSULIN STORED IN PLASTIC INSULIN SYRINGES FOR 28 DAYS

The stability and sterility of biosynthetic human insulin products stored at refrigerator and room temperatures in two types of plastic syringes and the stability of preservatives in the products were studied. Four types of biosynthetic human insulin were used: regular, isophane, combination, and extemporaneously prepared combination. Samples (0.4 mL) were withdrawn from multiple-dose vials into 39 polypropylene and 39 propylene- ethylene copolymer syringes. Three syringes of each type were analyzed immediately; the remaining syringes were stored in plastic bags, half at room temperature (23-degrees-C) and half in the refrigerator (4-degrees-C). A vial of each type of insulin was maintained under similar conditions. At days 1, 3, 7,14, 21, and 28, samples from each syringe were analyzed by high-performance liquid chromatography for insulin potency and m-cresol and phenol concentrations. Samples of each product were also tested for sterility after 1, 2, and 4 weeks of storage at 4-degrees-C and 23-degrees-C. The potency of insulin in each of the biosynthetic human insulin products did not change significantly during the 28-day study in both types of plastic syringes and at both temperature settings. m-Cresol concentrations decreased in all samples; greater decreases occurred in samples stored at room temperature and in samples stored in polypropylene syringes. Phenol concentrations were less affected than m-cresol concentrations; greater decreases occurred in samples stored at room temperature. No significant decreases in insulin potency or m-cresol or phenol concentrations occurred in control samples stored in vials kept under similar conditions. No microbial growth occurred; this finding suggests that the small loss of preservatives did not affect product sterility. The human insulin products studied remained stable and sterile during 28 days of storage at room and refrigerator temperatures in two types of plastic syringes. Because concentrations of the preservatives decreased more during storage at room temperature, prefilled syringes should be stored in the refrigerator.