Characteristics of commercially manufactured and compounded protamine zinc insulin

Abstract

To evaluate and compare characteristics of a commercially manufactured protamine zinc insulin (PZI) product and PZI products obtained from various compounding pharmacies. Evaluation study. 112 vials of PZI (16 vials of the commercially manufactured product and 8 vials from each of 12 compounding pharmacies) purchased over an 8-month period. Validated methods were used to analyze 2 vials of each product at 4 time points. Appearance, endotoxin concentration, crystal size, insulin concentration in the supernatant, pH, total insulin and zinc concentrations, and species of insulin origin were evaluated. All 16 vials of commercially manufactured PZI met United States Pharmacopeia (USP) specifications. Of 96 vials of compounded PZI, 1 (1 %) contained a concentration of endotoxin > 32 endotoxin U/mL, 23 (24%) had concentrations of insulin in the supernatant > 1.0 U/mL, and 45 (47%) had pH values < 7.1 or > 7.4; all of these values were outside of specifications. Several vials of compounded PZI (52/96 [54%]) did not meet specifications for zinc concentration (0.06 to 0.1 mg/mL for 40 U of insulin/mL, 0.075 to 0.12 mg/mL for 50 U of insulin/mL, and 0.15 to 0.25 mg/mL for 100 U of insulin/mL), and total insulin concentration in 36 [38%] vials was < 90% of the labeled concentration. Only 1 of 12 compounded PZI products met all USP specifications in all vials tested. Use of compounded PZI insulin products could potentially lead to serious problems with glycemic control in veterinary patients.