Abstract

Sterile filling of not terminally sterilized liquida – How much barrier does the process need?

The risk of contamination regarding the filling process of not terminally sterilized liquida is based on different sources of contamination. The human factor represents the greatest risk of contamination and can´t be completely separated from the process despite the technical and automatic progress. Due to the implementation of corresponding barrier systems it is possible to increase the separation degree and to separate the human factor almost completely in dependence of the barrier system design. The different barrier systems like conventional cleanrooms, RABS-Design and isolator technology have a significant influence on the zone concepts, process design, and quality and cost criteria.
The conventional cleanroom has the lowest separation degree between process and operator due to the laminar flow curtains but enables temporal advantages regarding interventions, process set-up and changing of format parts and especially the investment cost. The necessary effort regarding microbiologic monitoring, cleaning- and covering procedure for the clean room class „B“ requires very high operating cost. The different design variants of the „Restricted Access Barrier Systems“ enable a higher separation degree between process and operator and therefore also a higher product protection. But the RABS-design requires also a higher effort for construction, installation, qualification and limits the flexibility for interventions and changing of format parts. Due to the remaining need of clean room class „B“ background, it isn´t possible to intercept the higher investment costs with the lower operating costs. The isolator technology represents the greatest possible separation between process and operator due to the completely closed filling zone and the integrated decontamination cycle, but also requires the highest effort regarding planning, construction, installation, qualification and investment costs. The considerably higher investment costs and temporal losses at interventions and set up time could be intercepted with the savings at the operating cost due to the clean room class „C“ background. The isolator technology achieves the highest product protection against human contamination.

Korrespondenz:

Gerald Mathe, Boehringer Ingelheim Pharma GmbH & Co. KG, Dept. Manufacturing Respimat Germany, Binger Str. 173, 55216 Ingelheim, Germany, e-mail: gerald.mathe@boehringer-ingelheim.com