Pramlintide injection drug product robustness studies

Abstract

The article examines the effects of temperature excursions and actual dose withdrawal on the quality of pramlintide injection, a multidose liquid parenteral formulation. Studies were designed to demonstrate product robustness under conditions that may occur during patient use. Pramlintide %Purity was determined by two high-performance liquid chromatography (HPLC) methods, a reversed-phase (RP-HPLC) and a strong-cation exchange (SCX-HPLC) method. A second RP-HPLC method was used to determine pramlintide potency and the concentration of the m-cresol preservative. Antimicrobial preservative effectiveness testing was per USP and European Pharmacopeia (Ph. Eur.). Short-term stability studies were undertaken to probe the effects of the following conditions: 5°C to 40°C and 5°C to -20° C temperature cycling over 10 days; once daily or four-times daily dose withdrawal over 12 or 42 days; and combined 30° C storage and four-times daily dose withdrawal over 42 days. In all cases, pramlintide %Purity and potency values remained essentially unchanged or unchanged relative to controls. Similarly, product appearance, and m-cresol concentration and preservative effectiveness were not significantly affected by the stress conditions used in the 5 studies. Pramlintide injection drug product is extremely robust to challenging stress conditions that may occur during patient use of this multidose product for chronic administration.