Hello! I have a question about Media Fill test for vials:
Is it necessary to perform integrity test on 100% vials of MF batches before incubation during start-up aseptic process validation?
PIC/S recommends to validate integrity of the container-closure system during marketing authorization, and FDA guidance tells to do routine integrity inspection during production and don’t incubate vials with compromised integrity with other vials.
Is it technically possible to check 100% vials of validation batch (5 000), and then validate closure system and process?
If it’s possible - is it reasonable?
Thank you.
It is not possible to technically test integrity of 5000 vials in a validation batch.
It is possible to adjust your sealing head to a prescribed and predetermined pressures of sealing. Before you start your media fill exercise, you validate your filling line for its functionality.
You need to test the repeatability and robustness of sealing based on seal tightness and applied forces on your seals.
You will set the equipment to a determined value as per your experimentation.
During media fills you can pick randomly some samples out of 5000 vials, test the seal integrity by any one of the compendium methods or validated in-house method and document its authenticity.
[quote=dsorokin]Hello! I have a question about Media Fill test for vials:
Is it necessary to perform integrity test on 100% vials of MF batches before incubation during start-up aseptic process validation?
PIC/S recommends to validate integrity of the container-closure system during marketing authorization, and FDA guidance tells to do routine integrity inspection during production and don’t incubate vials with compromised integrity with other vials.
Is it technically possible to check 100% vials of validation batch (5 000), and then validate closure system and process?
If it’s possible - is it reasonable?
Thank you.[/quote]
How it is possible to check 100% of validation batches (5000) by microbial ingression / immersion method or dye immersion method.
Both methods you suggested are destructive methods.
I would prefer dye penetration test to microbial ingresion test.
The reason is dye test is quick and can be handled with minimum of interventions and Individual can see it with minimum expertise.
The recent developments by machine manufacturers made it possible to seal the vials with a specific force or seal pressure and which can me measured and recorded during every sealing.
The biggest drawback of dye ingress test is that they do show false positive results. One should know and identify such false positives.
ASTM F2338-05 is a Standard Test Method for non destructive Detection of Leaks in Packages by Vacuum Decay Method (Sterility). This can be effectively employed.
A popular method is a Tracer Gas testing. Here gasses like Carbon Dioxide, Helium and Hydrogen are used and this method can be 100% validated and calibrated.
Other popular non destructive tests are High voltage leak detection (HVLD) & Laser-based headspace detection test.
Thank you, you made it much more clear to me!