Broth fills microbial contamination

Extensive process simulation (broth fill) results for BFS effectively demonstrate that high levels of sterility confidence can be obtained with a properly configured and validated machine. However, in order to maintain high levels of sterility assurance, it is important that levels of microbial contamination are controlled within the filling environment. 

It can also be useful to retain and ineubate rejeet units filled during the course of a broth fill batch (again, excluding those that leak) for additional information. Again, these should be separated from aeeeptable units and labelled accordingly. Although such imits would be rejeeted during normal produetion, microbial contamination foimd in such imits may indicate a problem whieh requires attention. 

Prequency and size of broth fills must be clearly defined. The size of fill is usually based upon the statistical probability of detecting an acceptably low incidence of microbial contamination. Tables have been published to this effect [4], but the BPS operator has to decide both size and frequency of broth fills based upon their speeifie facility, routine product batch sizes, and operation. Por high speed BPS maehines used for filling routine produet batehes in excess of 100,000 units, broth fill batehes larger than traditional aseptic filling lines are both feasible and appropriate. 

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