Comparison of Compendial Antimicrobial Effectiveness Tests

Comparison of Compendial Antimicrobial Effectiveness Tests
Abstract
The antimicrobial effectiveness or preservative effectiveness test is described in the tripartite compendia for sterile parenteral multi-dose formulated products. The execution of the test is essentially harmonized with respect to inoculum preparation and test execution but not the acceptance criteria. This article describes how a single test can be performed that procedurally satisfies all of the compendia and their acceptance criteria.

TEST INTERVALS AND ACCEPTANCE CRITERIA
The acceptance criteria for the product type determine the time intervals at which the samples are enumerated for log reduction over the initial time zero inoculum levels. The three compendia are not harmonized with respect to acceptance criteria in terms of challenge reduction and the significance level that is expressed (4–6). However, one test can be executed that satisfies all time intervals and compendial acceptance criteria. The major difference for sterile multi-dose formulations is that the Ph. Eur. has 6- and 24-h time interval criteria while the USP and JP do not have criteria until days 7, 14, and 28 (4–6). Given these different criteria, enumerations performed at 6 h, 24 h, 7 days, 14 days, and 28 days after the initial microbial challenge satisfy all compendial requirements (4–6). These plate counts are converted to log10 and compared to the time zero enumeration performed on the saline control inoculum levels (4–6).

The Ph. Eur. (see Table VI) has the most strict acceptance criteria in that it requires a log reduction at 6 and 24 h for “Criteria A” preservative effectiveness (5). These criteria are difficult to achieve with many preservative systems. Often, the level of preservative added to achieve these results has detrimental effects on the product and/or is at toxic levels. The Ph. Eur. also has “Criteria B” that is considered mandatory by EU regulatory agencies and is more achievable (5). By 24 h, the preservative is expected to achieve at least a 1 log reduction and prevent proliferation throughout the 28 day period (5). The USP (see Table IV) does not have criteria for acceptance until day 7, and the JP (see Table VII) begins criteria at day 014 (4,6). The USP also defines “no increase” in proliferation as not more than 0.5 log higher than the previous measured level that corresponds to the expected plate count variability (4). Quality sterile multi-dose preparations should have a preservative that can rapidly prevent cell proliferation and destroy any microorganisms inadvertently introduced by multiple withdrawals of product throughout the product's use period. The USP chapter is an official test method and although AET is not a product release specification, the FDA requires products to meet the log reduction requirements in the chapter.
[from Comparison of Compendial Antimicrobial Effectiveness Tests: A Review by Cheryl L Moser and Brian K Meyer, https://pmc.ncbi.nlm.nih.gov/articles/PMC3066379/]

Comparison of Compendial Antimicrobial Effectiveness Tests

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