Changing gear: How to mitigate risks in cleanroom manufacturing

Juha Mattila, director, sterilisation technologies, STERIS Life Sciences, explains how to mitigate risks in cleanroom manufacturing for the sterilisation of goods, and highlights the growing trend of utilising automated and validated Vaporised Hydrogen Peroxide (VHP) material transfer decontamination.

Manufacturing sterilised goods is more than just the terminal sterilisation step at the end of the drug delivery device or other medical device manufacturing line. Quality of the end-product depends on the preceding process steps such as raw materials, cleaning, packaging, component sterilisation and material transfer to cleanroom.

Automation of pharmaceutical manufacturing processes, related operations, and material handling are driven by the constantly growing need to mitigate any risks associated in the production of drug delivery devices and other medical devices. Any manual processing activity presents a greater risk for the end-product quality, regardless if a process takes place inside cleanroom or isolator space, or if it takes place before entering the cleanroom manufacturing area. One such process is material transfer and its related decontamination process for minimising bioburden in material transfer into cleanrooms.

Material transfer of pre-sterilised components (e.g. stoppers, vials, syringe components) is carried out using sterilisation bags covered with one or more, typically LDPE, plastic bag layers. These enable protection of goods entering from lower classification areas to higher, such as going from D to C areas, or from C to B areas. Once entering an airlock, the bag surface is wiped with alcohol or another suitable disinfectant for minimising bioburden in transfer. When transferred to the other side, the bag outer surface is then removed, and the wiping of the possible next bag layer is repeated until the destination is reached (class A = isolator space).

The above described manual method is very time consuming, labour intensive and difficult or impossible to validate, as each process is always manual. Such a process is a true bottleneck for many pharmaceutical or medical device manufacturing facilities striving to continuously improve productivity and quality.

In response, automated material transfer using atmospheric VHP or generally VHP chambers has increasingly replaced manual methods. This technology provides greatly improved efficiency in decontaminating transferred bags, instruments and tools outer surfaces in both existing manufacturing operations and greenfield facilities that have been directly designed for using automated processes as much as possible.

VHP material transfer decontamination chamber cycles are manually loaded and un-loaded to carts or hooks on carts, and then pushed into the chamber. In continuous high capacity throughput systems, however, automated loading and unloading systems can be integrated to the chamber. A VHP material transfer decontamination process consists of three main phases: Preconditioning (de-humidification and possible conditioning), decontamination exposure (validated 10-6 log reduction result when using Geobacillus Stearothermophilus spore biological indicators), and post-conditioning (aerating the load by removing VHP residual by catalyser and turbulent airflow).

Typical cycle times vary between 45 and 100 minutes depending on the materials being decontaminated. Longer cycle times (over 60-70 minutes) are most often required for cellulose tags or partial covers of bags in the load, which may need prolonged aeration to reduce peroxide residuals down to allowed unloading PEL/OSHA levels of one to three ppm. Chamber sizes vary between small box-size dimensions to small cleanroom-size applications.