Why does Annex 1 expect a pre-use post-sterilization integrity test on sterilizing filters?

Why

A sterilizing-grade filter is the last barrier before an aseptically filled product, so its integrity has to be proven. Annex 1 says the integrity of the sterilized filter assembly should be verified before use, the pre-use post-sterilization integrity test or PUPSIT, to check for damage caused by preparation. It also says the filter should get a non-destructive integrity test after use, before it is removed from its housing.

Typical tests are bubble point, diffusive flow, water intrusion and pressure hold, and results should correlate with the bacterial retention shown in validation. The reason for testing before use is filter masking. If a filter is damaged during steam sterilization, a product with high particle load might plug the flaw during filtration, so the post-use test passes even though non-sterile fluid went through early in the run.

The pre-use test catches the damage before any product is at risk. The trade-off is that PUPSIT itself adds manipulations downstream of the filter, which can compromise sterility of the filtrate path. Annex 1 accepts that PUPSIT may not always be possible, for example with very small volumes, and allows an alternative if a thorough risk assessment covers filter sterilization control, supply chain and transport, and whether the product can mask a defect.

The US FDA's 2004 guidance says integrity testing can be done before processing and should routinely be done after use, so expectations differ by region.