A media fill is the simulation of an aseptic filling process with nutrient medium instead of product. The filled units are incubated, and every turbid container indicates a contamination. In this way a sterile site demonstrates that equipment, personnel and procedures do not introduce microorganisms into the product. For pharmaceutical companies, the media fill is therefore the most important evidence of a contract filler’s sterility assurance. This article explains the procedure, acceptance criteria and frequency.
Key takeaways
- In a media fill, sterile nutrient medium is filled under worst-case conditions and incubated for 14 days.
- Annex 1 requires at least two media fills per year and line, and the target is zero contaminated units.
- Clients should review the results of the latest media fills before approving a filler.
What is a media fill?
The media fill, also called aseptic process simulation, replaces the medicinal product with a nutrient medium, usually tryptic soy broth. The medium passes through all steps of the real process, meaning preparation, sterile filtration, filling, closing and handling. All units are then incubated. If the medium remains clear, the process has passed. The requirements are set out in Annex 1 of the EU GMP guide, section 9.
How does a media fill work?
| Step | Content |
|---|---|
| 1. Planning | Definition of line, container, batch size, duration and worst-case interventions in the protocol |
| 2. Preparation | Sterilisation of the medium, growth promotion test, cleanroom in routine condition |
| 3. Filling | Filling under routine conditions, planned interventions such as needle changes or stopper replenishment, maximum number of people |
| 4. Incubation | At least 14 days, usually 7 days at 20 to 25 degrees and 7 days at 30 to 35 degrees |
| 5. Evaluation | Visual inspection of every unit by trained personnel, documentation of all findings |
| 6. Report | Assessment against the acceptance criteria, root cause analysis in case of contamination |
Which acceptance criteria apply?
The target is zero contaminated units. Every contaminated unit triggers an investigation. For a media fill with fewer than 5,000 units, a single contaminated unit already means failure. For larger batches, a single contamination counts as an alert with root cause analysis, while two or more mean failure. A failed media fill means the line may not release commercial batches until the matter is resolved.
How often is a media fill carried out?
Before a new line is commissioned, three consecutive successful media fills are required. After that, Annex 1 requires at least two simulations per year and line. In addition, a media fill is due after significant changes, for example after modifications, new container formats or extended downtime. Every employee who works in the grade A area must take part in a media fill at least once a year.
What does worst case mean in a media fill?
The simulation should be more demanding than everyday operation. Therefore the longest process duration, the maximum number of people, the smallest and largest containers, breaks and all permitted interventions are planned in. A process that remains sterile under these conditions also remains sterile in routine operation.
What clients should check at the contract filler
- Protocols and reports of the last two media fills per line
- List of simulated interventions compared with the interventions in the real process
- Evidence of growth promotion of the medium
- Participation of personnel and qualification status
- Handling of deviations and results of root cause analyses
Media fill at Lubeca fill
Lubeca fill was founded in 2019 and fills sterile liquids into ampoules, vials and bottles in Çorlu near Istanbul. The equipment comes from Groninger, Bausch + Ströbel and Syntegon. As part of the preparation for EU GMP certification, the aseptic processes are simulated and documented in accordance with Annex 1. Which other requirements Annex 1 sets is explained in the article on Annex 1. How to review the documents in an audit is shown in the article on GMP audits.
Frequently asked questions about media fills
How many units does a media fill include?
The batch size should correspond to routine production. Typically 5,000 to 10,000 units, or correspondingly fewer for small batches.
What happens if the media fill fails?
The line is blocked and a root cause analysis follows. After corrective actions, three successful simulations are required again.
Does the media fill replace the sterility test?
No. The media fill demonstrates the suitability of the process, while the sterility test checks the individual batch.
Would you like to review the media fill documentation of Lubeca fill? Contact us.
