Process simulation

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.