At least twice a year, each filling line used for aseptic production is requalified at Rechon. Using methods established in 2000, we have now tested 300 000 units in a row for bacterial contamination – without a single positive sample.
Process simulation tests, so called media fills, are performed for two reasons:
• to validate an aseptic process
• ensure that the processes used are able to produce a product free from microorganisms.
To initially qualify a filling line at Rechon, at least three consecutive approved media fills are required. Thereafter each filling line used for aseptic production is requalified with media fills at least twice per year.
The test is performed by filling the units – i.e. vials, ampoules or syringes – with a microbiological growth medium instead of product solution. The filled units are then incubated and eventually visually examined for evidence of microbiological growth. The media is tested for growth promotion.
During a media fill, at least 5000 units are tested. The units are filled and incubated for at least 7 days in 20–25°C, followed by at least 7 days in 30–35°C. After that, they are visually examined for evidence of growth. No contaminated units are accepted and if a contaminated unit is found an investigation is immediately initiated.
The media fill should simulate the production process as closely as possible and should include worst case conditions. The same or identical production equipment is used as for the products filled on the line.
Worst case conditions that are included in the qualification are for example
• holding time for bulk solution between filtration and filling
• holding time for sterilised equipment
• number of interventions
• number of operators
• type of interventions
• filling time
• line stoppages
Each operator participating in aseptic filling is qualified with media fill before filling of product and is thereafter requalified on a routine basis.