Process simulation studies should be designed to emulate the routine production process as closely as possible, including formulation, filtration and filling stages. Processes will vary in relation to the type of product to be filled, e.g. liquid or solid dosage forms, and each process simulation is a unique event whereby extrapolation of outcomes cannot be directly linked to actual process contamination rates.
The study will be performed using microbiological growth media in place
of active pharmaceutical ingredients (API). This is a 'worst case'
senario as most pharmaceutical products normally would not support
microbiological growth. The selection of the medium should be based on
its ability to integrate into the process at the earliest formulation
stage and therefore have the capacity to be introduced to the filling
process by filtration. Also the growth promotion characteristics should
allow recovery of the typical flora recovered from environmental
monitoring programs. The microbiological culture media itself can
potentially be a source of contamination so to avoid a culture media
related positive fill test, the media is irradiated and can be presented
either in the dehydated format or as a ready to use broth.
Modern culture media, designed for media fill trials, possess certain
attributes that facilitate process simulations; they will be irradiated
making them suitable for introduction into compounding areas, will
dissolve in cold water and have known filtration performance as standard
broth can be slow to filter or block the filter. Also, those who wish
to use an animal-free product can now obtain a vegetable alternative.
Following formulation, filtration and filling the closed vessels are incubated and inspected for contamination.