A Review and Comparative Study of Preservative Efficacy Test in the United States, European, Indian, and Japanese Pharmacopeias and Implications for Asian Pharmacopeias

Introduction: The preservative efficacy test (PET) is a critical tool for assessing the ability of antimicrobial preservatives to prevent microbial contamination in pharmaceutical products, ensuring their safety and stability during production and storage. This study reviews and compares PET standards across four major pharmacopeias—the United States Pharmacopeia (USP), European Pharmacopoeia (EP), Indian Pharmacopoeia (IP), and Japanese Pharmacopoeia (JP)—to identify disparities and propose harmonization strategies, with a focus on implications for Asian pharmacopeias. Methods: We systematically compared the PET protocols of the USP, EP, IP, and JP, focusing on product classification, challenge microorganisms, culture media, sample contamination methods, incubation conditions, and acceptance criteria. Data were extracted from the latest editions of each pharmacopeia and analyzed for differences in stringency and methodology. Results: Significant variations were identified across the pharmacopeias. For example, the USP requires an inoculum of ۱۰۵ colony-forming units per milliliter (CFU/mL) for certain organisms, while the EP specifies ۱۰۴ CFU/mL. Challenge organisms also differ, with the USP mandating Pseudomonas aeruginosa and Staphylococcus aureus, and the EP including a broader range, such as Aspergillus brasiliensis. Acceptance criteria vary, with the USP requiring a ۳-log reduction in Escherichia coli within ۱۴ days, compared to the EP's ۲-log reduction over the same period. Incubation periods range from ۱۴ days (USP and IP) to ۲۸ days (JP), potentially affecting drug quality assessments. Conclusions: These disparities in PET standards may lead to inconsistencies in drug quality and safety across regions, particularly in Asia, where harmonization with global standards is limited. We recommend the development of a unified international framework for PET, incorporating the USP's stringent log-reduction criteria and the EP's comprehensive microbial selection, to enhance global drug safety. For Asian pharmacopeias, adopting such harmonized standards could facilitate regulatory alignment, improve product quality, and support international trade.

کلیدواژه ها:

Pharmaceutical Preservative ، Pharmacopeia ، Preservative efficacy test ، USP ، Microbial Challenge Testing ، Antimicrobial Efficacy ، Staphylococcus aureus ، Pseudomonas aeruginosa ، Candida albicans