Media fill Test Assurance of Sterility of parantral dosage form Injectables

Assuring the sterility of injectables sterile dosage form is very critical and must .Each and every container produced in a batch of a parentral dosage form should be sterile, even it is not possible to test each and every containers of a batch of parentral dosage form for sterility ,but enough evidence can be produced to claim the product as a sterile.
Media fill test is a toll to ensure the integrity of the process , environment , machinery and facility.
Parentral dosage forms manufacturing facilities should adapt the concept of Quality by design in their process , machinery’s and formulations.

Even FDA has given lot more stress on sterile dosage form in the guidelines issued to pharmaceutical industries.
There is much scope for development in this field .

Media fill make use of culture medias instead of actual products , this process is carried out to evaluate the process along with machinery’s being used for manufacturing of sterile dosage form .
Small change in the process can give variable results in media fill test.

Media fill make use of a suitable microbiological media , in place of actual product .
This media is filled as that of actual product is being filled , by following exact steps , as that of actual product , starting from dispensing to compounding to sterilization , filtration , autoclaving and storage .

Media fill test or process is designed to evaluate following points in manufacturing of parantral dosage form

1.Facility and room design
2.Design of filling machine
3.Flow of the manufacturing process
4.Heating , ventilation , and air conditioning Design and validation.
5.Utility design and validation
6.Response to any deviation
7.Trends in environmental monitoring data.
8.Decontamination program (Contamination control ) cleaning and sensitization .
9.Process simulation
10.Personal training and Qualification.

Following key points should be considered for exact simulation of media fill run

1.Type of product being filled.
2.Batch size of product
3.Containers and closures
4.Fill volume
5.Filling line speed.
6.Personals (Operators, working shifts )
7.Filling line configuration
8.Sterile hold time.
9.Number of units being filled , actual production quantity simulation.
10.Acceptance criteria.
11.Run duration
12.Interventions.
13.Elements which affect assurance of sterility

Worst cases should also be considered to evaluate integrity of manufacturing process and its validation , worst cases should not be the worst , they should be , the cases which may occur while in regular process .

Selection of growth media for Media fill runSelection of growth media for media fill run is very critical , I will like you to read my earlier article where I have written about a case where media fail test results were failing where as actual product did not failed.
That was because of growth media ,
Never the less media should support the growth of wise range of microorganisms,
Including aerobic bacteria , anaerobic bacteria , yeasts , molds , fungi.

Microbial environment monitoring program results should be considered for selecting the range of media to support the growth of a particular organism.
FDA has recommended use of soybean casein digest media well known as Tryptone soya broth.
Due to risk of precontamination of such media , demand your suppliers required clarification and certification for “BSE free” Oxoid cold filterable Tryptone soya broth.

FDA guidance also make it clear that if the product is being filled in nitrogen environment , and anaerobic medium should be used , Example .Fluid thioglycollate .

1.Prefer a media which is presterilised by radiation for your media fill run.
2.Select a media which dissolves at ambient temperature.
3.Avoid medias with mycoplasma.
4.Media should be filterable , should not block the filters .This is very important , otherwise , the process could not be simulated.

Media fill Run Process

The process should be simulated , exactly at the same point as that of product the medium should be introduced to process , just as the product is filtered and used , media should be filtered and introduced in to line .

Perform the growth promotion test on media on conclusions drawn from incubation period of 14 days.
All the units that are incubated after filling should be inspected for any defect , as that of a regular product,
Document the quantities of rejection with reasons .
Incubation is done for 14 days at 20 to 35 °C + 2.5 °C
All units should be incubated in inverted position.for first 7 days and then in up right position for 7 days .
Microorganisms isolated in Environment monitoring program should also be picked up by Media fill run.

A case study where Media fill run failed
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