Tuesday, April 25, 2023

Media fill sterile dosage form filling validation

Important points for media fill sterile dosage form filling validation: Media fill is an activity of giving proof that the filling equipment, filling area, manpower working in the sterile dosage form filling area do not cause any contamination during filling of a sterile product batch. Media fill run is a type of validation of sterile filling activity machine as well as man and aseptic process. 

Media used for media fill is soybean casein digest medium: Before the media fill run, the vendor of the media is required to be approved. In order to approve the vendor for media, media is tested for its quality, growth promotion test, PH 7.3 (±0.2), etc. Growth promotion test of media is done by selecting any one microorganism from the list of the microorganisms listed in USP under the test of growth promotion test for media. 
Media is prepared sufficient to fill the bottle which represents the sufficient volume of the product batch size and sufficient for time required to capture every minute details of operation is mimicked during the media fill. Gowning which the operators are going to use is sterilized before the media fill, the filling machine, line, nozzle and pipes storage vessels are cleaned and sterilized by autoclaving. Vessels are autoclaved and sterilized. Floor and ceiling of the room is cleaned and decontaminated. 

The number of manpower participating in the media fill is almost equal to the actual filling line run. Area is cleaned and disinfected, by fogging hydrogen peroxide, and de-ariation is done by running AHU for cleanup time. The surfaces of machines and equipment are decontaminated, with suitable decontaminating agents. 
Entire filling area is prepared for the actual product filling. Pre Sterilized primary containers and closures are taken inside the filling area by regular routine procedure. What is not done during media fill? Media should not be terminally filtered before addition to the primary product container, if that is done, the microbial contamination from the filling machine may not get added and it will lead to false negative results. 

Media should be sterilized by autoclaving before filling on the filling machine, exact steps like transfer to the filling area, connection to the filling line, and actual filling should replicate the actual filling process, there should not be any additional step like filtration etc. should not be allowed. 

A new operator or untrained person should be avoided, the persons who do actual sterile product filling run are required to present for media fill run. An operator should be present for three consecutive days for media fill validation. An operator at least for once in a year must participate in the media fill. Media fill should be done on the actual place in the clean room where the product is filled. The place of the media fill should not be changed. 

When to do media fill run? Media fill run is done in following events:
 1.Durring addition or startup of new products to the manufacturing area. 
 2. If any changes are done in the filling line, area, or after change of heap filters. 
 3. After a change of manpower, in the filling. Change of operator. 
 4. Change of the disinfection, decontamination procedure, change of cleaning procedure. 

 Positive control test during media fill: A positive control is kept during media fill, by inoculating almost less than 100 number of microorganisms from standard culture of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa (any one microorganism from these three is selected for positive control test). Positive control is kept to just show that the media is capable of supporting the growth of any microorganism if it gets trapped in media during feeling. Positive control media is not required to pass through the filling line. 

 Negative control test during media fill test: Negative control of media is kept, to show that the media is sterile and do not have any contamination from media itself, The negative control too is not required to be passed through filling line, also it can be kept in a pre-sterilized plates, the container that is being taken for media fill is not required to be taken to exhibit negative control. Incubation of media feel: Media feel containers are stored preferably at 20o– 25oC for the aerobic growth medium at temperature 20o and 35oC ±2.5oC. Incubation period of media fill is not less than 14 days, every 3 days all containers are required to be checked for growth.

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