Microbial contamination bioburden testing

As with traditional aseptic filling, in order to comply with pharmaceutical GMP, it is important to minimize contamination at all stages of manufacture. Raw materials should be of a high quality and tested for microbial contamination. Water used for product manufacture should be of low bioburden and high purity (preferably water-for-injection quality, although this requirement is dependent upon the nature of the product being manufactured). 

In general, bioburden counts in parenteral solutions are obtained by conducting the total aerobic counts and total yeast and mold counts as specified in the USP microbial limits test (61) or an equivalent test [72], In addition, membrane filtration of larger than specified volumes may also be used to detect any microbial contamination when sample results are expected to contain a negligible number of microbial flora or in the presence of potential confounding factors, such as antimicrobial... 

Preservatives are intended to offer further protection against environmental microbial contaminants. However, as they are relatively non-specific in their reactivity (see section 7), it is difficult to calculate with any certainty what proportion of preservative added to all but the simplest medicine will be available for inactivating such contamination. Laboratory tests have been devised to challenge the product with an artificial bioburden. Such tests should form part of formulation development and stability trials to ensure that suitable activity is likely to remain throughout the life of the product. They are not normally used in routine manufacturing quality control. 

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