Process simulation studies (media fills) are simulating the whole process in order to evaluate the sterility confidence of the process. Process simulation studies include formulation (compounding), filtration and filling with suitable media.
Simulations are made to ensure that the regular process for commercial batches repeatedly and reliably produces the finished product of the required quality. However, each process simulation trial is unique and so it is not possible to extrapolate these results directly to actual production contamination rates.
Two simulation methods are commonly used in the lyophilizer. In the first one a dilute medium is subject to a cycle that removes water until a determined medium strength is obtained, but is not subject to freezing.
The second method uses full strength medium and requires only a partial vacuum be drawn whilst the chamber should be kept at ambient temperature. There is a risk that the medium may boil over and contaminate the chamber unless conditions are tightly controlled. The absence of boiling under the defined cycle conditions should be confirmed.
Vacuum break in lyophilizer is recommended to do with a sterile air by major regulatory body. Use of nitrogen can affect the growth of microorganisms or better to say growth promotion properties in media. Hence you can get a false negative growth in the filled unit. So, it is not accepted doing vacuum break through nitrogen in lyophilizer .