Validation of aspect processing should increase a process stimulation test using nutrient medium called media fill. A media fill is one part of the validation of an aseptic manufacturing process. The goal of a media fill is to test whether the aseptic procedure is adequate to prevent microbiological contamination during the actual process. Media   fills may be used to evaluate aseptic techniques used in the assembly of pre-sterilized components and to qualify operators for aseptic techniques.


What is a media fill?

A “media fill” (sometimes known as a “process simulation”) is the performance of an aseptic manufacturing procedure using a sterile microbiological growth medium in place of the drug solution. Microbiological growth medium is used in place of the drug solution during media fills to test whether the aseptic procedures are adequate to prevent contamination during actual drug production. 


How to select medium for this test?

Selection of nutrient medium should be made based on dosage form of the product and selectivity, clarity, concentration and suitability for sterilization of nutrient medium.


When this test should be performed?

This test or an equivalent test is performed at least annually by each person authorized to compound in a low-risk level environment under conditions that closely simulate the most challenging or stressful conditions encountered during compounding of low-risk level CSPs.

The process of simulation test should be performed as part of validation by running three consecutive satisfactory simulation tests. These tests should be repeated at defined intervals and after any significant modification to HVAC system, equipment or process.


Which Medium good for this process/usually used?

Soybean–Casein Digest Medium (also known as trypticase soy broth or trypticase soy agar [TSA])


How much size should be validate it?

The number of containers used for media fills should be sufficient to enable a valid evaluation. For small batches the number of containers for media fills should at least equal size of product batch.


Incubation period for this medium?

Incubated at 20° to 25° or at 30° to 35° for a minimum of 14 days. If two temperatures are used for incubation of media -filled samples, then these filled containers should be incubated for at least 7 days at each temperature


How many units should be pass for satisfactory results? 

The target should be zero growth;

* When filling fewer than 5000 units, no contaminated units should be detected.

* When filling 5000-10000 units:

1. One contaminated unit should result in an investigation, including consideration of repeat media fill;

- 2 contaminated units are considered cause of revalidation.


Reference: 

  • WHO annex 6 Good Manufacturing Practices for sterile Pharmaceutical Products.
  • USP: <797>PHARMACEUTICAL COMPOUNDING—STERILE PREPARATIONS
  • USP: <1823> POSITRON EMISSION TOMOGRAPHY DRUGS—INFORMATION


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