The media fill, also known as Broth fill, is a method whereby microbiological nutrient medium of growth is created and then filled in a simulation a usual manufacturing operation.
Usually, a microbiological medium of growth like SCDM (Soybean-Casein Digest Medium) is processed and then managed in a way that simulates an ordinary manufacturing process with similar kind of exposure and potential contamination. Incubation is performed in the final container.
This container is then monitored for turbidity- an indication of microbial contamination. Put in the simplest terms, this is exactly what transpires.
Media fill validation is required by the regulations of pharmaceutical. This is for a number of good reasons.
First and foremost, a sterile product is normally defined as being void of the viable organism. Since there is no practicality of examining every unit for the purpose of confirming sterility, efforts are made to reduce the risk of contamination. Some of these efforts include finishing, pressure differentials, HVAC, cleaning procedures as well as monitoring relevant programmes.
Irrespective of the numerous precautionary measures being implemented, contamination is always present.
This is primarily because aseptic processing is an operation being done in a controlled environment (but non-sterile) and the sample numbers are also extremely small. This means that only gross contamination is most likely to be detected.
Another reason for media fill validation originates from the fact that, although aseptic manufacturing conditions must be duplicated, it is impossible for them to be performed in an exact way as the manufacturing process of producing a batch of pharmaceutical products.
Further, when it comes to aseptic processing, the biggest risk emerges from the labor force working in the clean room. Typically, the operators must participate in the media fills. Also, it is important for environmental monitoring activities to take place during the operations of aseptic filling. The environmental monitoring activities include:
– The regulatory references dictating the microbial conditions
– The process of air sampling with the help of either passive or active sampling methods at the time the process is being executed. Surface sampling should also be conducted at the end of the process.
– Monitoring of the personnel during aseptic processing
– Microbiological monitoring which includes air, personnel and surfaces
– Particle monitoring must take place at the time of media fill
– The routine procedure should be observed strictly when there is a need to increase the number of sampling locations
It is a normal thing to take into account the worst case conditions that could happen in the production runs.
The goal of media fill validation protocol is to create documented evidence the process used for aseptic processing is capable of producing the anticipated results in a consistent manner- within the stipulated limits when conducted according to the most recent standard operating procedures. The validation protocol essentially describes the overall procedure for media fill.
Below are standard steps for validating the integrated line using media fill test. They include:
1. SVP Line cleaning.
2. Dispensation of Soybean Casein Digest Medium for a batch size of 150 L.
3. Preparation of batch 150L.
4. Filling, followed by Sealing.
5. Incubating the final container and examining the media filled units.
6. Interpreting the results.