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Use of Statistical Tools to Monitor Bioburden Levels in a Manufacturing Process
View Presentation View Presentation Lisa Musmanno, Grifols Therapeutics, Inc. 
*IRV SHIFFER, Grifols Therapeutics, Inc. 

Keywords: process control, non-parametric methods, basic probability, summary statistics, non-conventional approach

A common procedure for monitoring in-process bioburden levels is to set Alert and Action limits based on upper percentiles (such as 95th and 99th) of a set of historical data. This alternative statistical method considers that the values in the upper portion of the distribution are often produced by strings of high test results relating to some process event. The method is designed to identify these strings early and systematically, offering an opportunity to identify their generators and maintain the process at lower bioburden levels. A limiting “Threshold” value for the process’s bioburden capability during routine, satisfactory operation is determined. The rate of excursions above the Threshold is tracked, and Alert/Action signals are given when there is statistical evidence that the rate of occurrence has increased. The monitoring procedure includes a “Single-Event Action Limit,” based on the history of excursions, that signals a need for immediate investigation. This approach to bioburden monitoring is a convenient tool for day-to-day evaluation of process performance that has been demonstrated to improve operational efficiency.