Sterilisation of a new generic specialty in an isolator: matching routine and emergency procedures

The marketing of “over-packed” generics (Oncosafe, Ebewe laboratories) led to questioning the matching of that form of presentation with our qualification and sterilisation procedures. The medical device in which the bottle is placed is a polypropylene, biodegradable outer fitted with a screw cap enabling the product to be handled without having to touch the bottle directly. That protection restricts the dissemination of the outer contamination carried by the bottle. Direct exposure of the bottle requires removal of the cap from the outer. However, the space between the bottle and the base of the outer may be an obstacle to the dissemination of the peracetic acid despite the over pressure in the isolator. We therefore wanted to validate the integration of this new pack in our sterilisation procedures.

Upon the installation of the Centralised Reconstitution Unit (CRU) qualifications (CQ), IQ, OQ, PQ) of the production system were performed with the isolators in over pressure with storage. Among other things, the OQ required the development of sterilisation cycles with determination of the 100% lethality times. Our sterilisation airlock was tested with a maximum load, giving relatively long 6 log or 100% lethality sterilisation times (90 minutes) and in an emergency configuration with a lighter load giving shorter times (37 minutes). For safety reasons related to the heterogeneity of the loads, the in-house procedures implemented mean that these basic 100% lethality times (12 log sterilisation according to EN 550) have to be doubled. In each of the two configurations, we shall therefore test the 2 time periods corresponding to a 6 log and 12 log destruction.

We used Spordex strips (from AES Chemonex laboratories) on which 106 spores of Bacillus Stearothermophyllus were placed. The strips were inserted between the bottle (Doxorubicin 50 mg) and its outer, either laterally or under the bottle. For the two set-ups, 5 bottles were tested for the “emergency” configuration and 15 for the “routine” series, arranged in a classic load.

In the “emergency” configuration, the strips remained positive at 6 log (37 minutes) and at 12 log (75 minutes) whether they were placed laterally or on the bottom of the bottle.

In the “routine” configuration, the strips remained positive at 6 log (90 minutes) but became negative at 12 log (180 minutes), whether placed laterally or on the bottom of the bottle. A qualification was performed for this series with 3 tests.

This study enabled us to refine our in-house procedures. For routine series, the negative effect at 12 log means that the bottles are arranged in our loads with their outer. The difference in the results at 6 log and 12 log is acceptable taking account of our qualification based on the absorption of the heterogeneity of the loads. In the emergency configuration, the bottles are removed from their outer and sterilised bare.