Preservative efficacy testing of refrigerated pharmaceuticals: choice of challenging isolate and storage temperature

Abstract

The antimicrobial effectiveness testing assesses the performance of preservatives and/or antimicrobial substances added to multi-use sterile or non-sterile dosage forms, protecting these products from microbiological growth. In this study, insulin products underwent the European Pharmacopoeia and the United States Pharmacopeia antimicrobial preservative effectiveness tests at both room and refrigerated temperatures. Notably, a psychrotolerant strain, Serratia marcescens, originally isolated from a refrigerated pharmaceutical product, was included in the antimicrobial effectiveness testing. When evaluated against the compendial requirements, both NPH and REG insulin stored at room temperature successfully met the European Pharmacopoeia-A criteria and the United States Pharmacopeia standards. However, although both formulations stored under refrigeration conformed to the United States Pharmacopeia criteria, they failed to satisfy the European Pharmacopoeia-A criteria at contact times of less than 7 days. The reductions in Serratia marcescens counts were the same at both incubation temperatures. This study indicated that for sterile multi-dose vials, performing the antimicrobial effectiveness testing at both room and refrigerated temperatures might give more accurate indication of antimicrobial preservative efficacy.