A Generalized Plate Method for Estimating Total Aerobic Microbial Count

Abstract

The plate method outlined in Chapter 61: Microbial Limit Tests of the U.S. Pharmacopeia (USP 61) provides very specific guidance for assessing total aerobic bioburden in pharmaceutical articles. This methodology, while comprehensive, lacks the flexibility to be useful in all situations. By studying the plate method as a special case within a more general family of assays, the effects of each parameter in the guidance can be understood. Using a mathematical model to describe the plate counting procedure, a statistical framework for making more definitive statements about total aerobic bioburden is developed. Such a framework allows the laboratory scientist to adjust the USP 61 methods to satisfy specific practical constraints. In particular, it is shown that the plate method can be conducted, albeit with stricter acceptance criteria, using a test specimen quantity that is smaller than the 10 g or 10 mL prescribed in the guidance. Finally, the interpretation of results proffered by the guidance is re-examined within this statistical framework and shown to be overly aggressive.