Consideration of media fill tests for evaluation and control of aseptic processes: a statistical approach to quality criteria.

The concept of upper and lower statistical confidence limits has been introduced to the current media fill tests used for the assurance of aseptic operation. Results of media fill tests can be evaluated with rationale and interpreted more clearly by introducing the upper and lower limits for the number of observed positive units. Quality criteria derived by the misuse of statistics should be reconsidered. Media fill tests are one of the most useful methods for the evaluation of aseptic filling processes, and acceptance criteria have been issued in various official compendia. In some official compendia, various combinations of the number of media fills and the number of detected allowable contaminated units have been indicated based on the misuse of statistics. This study has statistically revealed that the larger number of fills allows for the worse average accepted quality. This study has shown that media fill tests can be used for the evaluation of aseptic operation with fully scientific and statistical rationale by evaluating the statistical lower limit for the number of positive units observed. This study proposed that the new criteria should be simply expressed as the process should be in a controlled state and can manufacture product whose sterility can be statistically assured with 95% confidence level.