Aseptic Process Simulation Media Fill Process Simulation Media

Aseptic Process Simulation (Media Fill)

Process Simulation (Media fill) A media fill is the performance of an aseptic manufacturing procedure using a sterile microbiological growth medium, in place of the drug solution, to test whether the aseptic procedures are adequate to prevent contamination during actual drug production. Purpose: Purpose of this media fill or process simulation is to demonstrate the capability of the aseptic process to produce continuously and consistently a sterile drug product & in parallel qualify the personal & environment involve in this process

Regulatory reference (Media fill) • ISO 13408 -1: 2008 states “Process simulation shall cover all parts of the aseptic process and include all aseptic manipulations. It is possible to divide the process into unit operations but all parts of the process shall be simulated (Clause 10. 1. 1) • 21 CFR 211. 113 : To ensure the sterility of Products Purporting to be sterile, both sterilisation and aseptic filling and closing operations must be adequately validated • EU GMP Annex- 1 : Validation of aseptic processing should include a process simulation test using a nutrient medium (media fill). Selection of the nutrient medium should be made based on dosage form of the product and selectivity, clarity, concentration and suitability for sterilisation of the nutrient medium.

Aseptic Process simulation Aseptic process simulation should be done in following condition; § Initial aseptic process qualification At least three trial should be taken to ensure that results are repeated and meaningful. • Re-qualification • Normal aseptic process simulation test should be repeated at least twice in a year • In case of modification in process equipments, HVAC system and number of shift operation

General Guidance for Aseptic Process simulation Ø Validation of aseptic processing should include a process simulation test using a nutrient media which support in the growth of all the microorganism. Ø Include all the critical manufacturing steps. Ø Take into account all the interventions which can occur during normal operation. Ø Number of container use for media fill should be sufficient to enable a valid evaluation Ø For any run size, intermittent incidents of microbial contamination may be indicative of low-level contamination that should be investigated.

General Guidance for Aseptic Process simulation Ø It should be demonstrated that air-flow patterns do not present a contamination risk, e. g. care should be taken to ensure that air flows do not distribute particles from a particle generating person, operation or machine to a zone of higher product risk. Ø Where filling takes place over extended periods, i. e. longer than 24 hours, the process simulation test should extend over the whole of the standard filling period. In order to prevent excessively high numbers of units being filled it is usually acceptable to just run the machine for a reasonable time, if the validity of the simulation is not diminished by this procedure. Ø Inert gas should not be use in the vial / container as its prevent the growth of microorganism. In place of inert gas filtered oxygen can be use.

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