Saturday, April 22, 2023

Media fill run process simulation aspects Validation of Aseptic Process

What is Validation of sterile drug filling aseptic process?

Media fill in aseptic process validation: Bacteriological media is taken for filling on the aseptic filling line, media is filled using the pre sterilized primary containers and closures, and the finished product pack is incubated at the temperature condition in the incubator as required for the bacterial and fungal growth. Media fill is a method to validate aseptic sterile drug filling equipment and area.

If at all there are any contaminants getting added in the filling line due to man or faulty cleaning and sterilization procedure, equipment, there will be a bacterial growth observed in the filled media. That is considered a media fill fail.

And if there is no growth observed or the results are well within the permitted limit then it is said that media fill is passed.

Sterile dosage form filling:

Sterile dosage form filling equipment and area are expected to, not to add any bacterial or microbial contamination into the product during filling. To assure that the cleaning and sanitization sterilization process adapted for filling equipment does not add any viable contamination is a challenge, Media fill run is an experiment to exhibit that the filling line does not add to any microbial contamination.

Why does the media fill.?

This gives a clear picture of the sterile filling line whether the filling line is completely sterile so that if the product is filled by adapting the same filling line and procedure and same operators will produce the sterile product without adding any contaminants into the product and the product will remain sterile after filling.

Which Media is used for media fill?

Soyabean Casein digest media (SCDM) is used for media fill; this media supports growth of almost all microorganisms including fungus.

What is positive control in media fill?

It is required to exhibit that the microbiological media used itself is capable of promoting the growth of the bacterial and fungal cell. This is done by inoculating the standard known microorganism into the filled container in the microbiology lab under LAF.

What is negative control in media fill?

It’s important to exhibit proof that the media used for filling is sterile and that any growth obtained after media fill is not due media, for this reason a sterilized media is incubated; this is called negative control.

Which are important points during the media fill run? Personnel requirement of media fill.

When a person becomes qualified for an aseptic filling process?


Rules for media fill in sterile dosage form aseptic filling process validation:

1)      Media filling should actually be done as that of the actual batch of the product adapting the same procedure, it should mimic the same operation as that of actual product filling.

2)      The Media fill should be done at the actual filling spot on the equipment where it is done in routine.

3)      All the operators must participate in the media fill run.

At least once in a year an operator should participate in a media fill run.

4)      Media fill should be done for three consecutive days in continuation.

5)      Media fill should be done as and when there is change in the equipment design or the new operator taking over the activity. Procedure of sterilization is changed or addition of a new product.

6) An operator, supervisor is certified to be qualified for filling up on participating in a successful media fill run for three consecutive days.

7) All the personnel involved in sterile dosage form filling are required to participate in the media fill run.

8) Before the media fill, the media should be tested for growth promotion tests.

9) Media used in the media fill should be from an approved vendor.

10)  Any one microorganism is used for growth promotion tests and positive control.

       Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa.  

Growth promotion test is done on media in isolated manner, while positive control is more or less same but the media sample inoculated challenged microorganisms are incubated along with the media fill samples.

What is bacteriological and fungal, growth promoting media?

Microbiological Nutrient media consist of high protein containing items like beef extract, yeast extract, soybean digest, casein digest, sodium chloride and water. These mediums promote the growth of a single bacterium into a colony of bacteria, or fungi, which are then visible to naked eyes as a colony.

Typical composition of a nutrient broth is as follows:

Distilled water, 500 ml Beef extract 0.5 gm, Yeast extract 1 gm, Peptone 2.5 gm Sodium Chloride 2.5 gm.

The difference between the nutrient broth and nutrient agar is that nutrient agar contains Agar 7.5 gm per 500 ml in addition to the all items of nutrient broth.

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