Risk of false compliance/non-compliance decisions for sterility test due to false-negative and false-positive test results

Abstract

The sterility conditions of pharmaceutical products should consider the manufacturing conditions and the result obtained from a sterility test. The statistical and analytical limitations of the sterility test may lead to false-negative or false-positive results. Experimental determination of the probability of false-negative and false-positive results requires a very large number of assays, which may be impracticable. Thus, the aim of this work was to estimate the risk of false decisions related to sterility test due to the false-negative or false-positive test results, using a theoretical approach. The probability of false-negative results was estimated by considering the expected level of contamination in the sample, the tested volume for each item, the total volume of each item, and the number of tested items. The probability of false-positive results due to environmental contamination was estimated by considering the microbial load per plate, the sampled air volume, the total volume of the safety cabinet, the number of air changes per hour, and the volume of the test tube used in the sterility test. A MS-Excel spreadsheet provided in supplementary material can be used to estimate the probability of false-negative or false-positive test results. The probabilities of false-negative and false-positive results considering the experimental conditions were found to be 0.0045% and 0.070%, respectively. The probabilities of false-negative or false-positive test results may be combined with previous knowledge about the probability of a non-sterile lot (Sterility Assurance Level – SAL) using the Bayesian approach. The Bayesian approach allows the risk of false compliance/non-compliance decisions to be estimated. Risks to consumer and producer are significantly affected by prior knowledge of the sterility assurance level.