Clean getaway: Steris Finn-Aqua talks best sterilisation methods for GMP
Juha Mattila, Steris Finn-Aqua, discusses VHP low temperature sterilisation in both material transfer and terminal sterilisation, to cover both GMP sterilisation applications.
New mindset for safe and efficient material transfer
Material transfer to classified aseptic manufacturing cleanroom areas (grade A or grade B) is under growing pressure to improve control and efficacy. The most common bio-decontamination technology used is VHP (vapourised hydrogen peroxide) under atmospheric and room temperature conditions. Equipment design for low-temperature bio-decontamination of material bags, components, electronics and various manufacturing tools and devices, needs to be in alignment with its purpose.
Pharmaceutical manufacturing needs
Conventional methods include manual operations to wipe material transfer bags and containers with alcohol or another disinfectant, and transfer of the wiped material through an airlock. Such procedures lack automation and consistency, in addition to being labour-intensive and time-consuming. Conventional material transfer can become a significant bottleneck that may hinder production growth of the manufacturing facility. Manual activities are likely to transfer particles to the cleanroom area.
Consistent processing requires developing production cycles for empty, partially loaded and full chamber with variable load configurations. Chemical and biological (106 CFU Bacillus Stearothermophilus) indicators are used for cycle development, and biological indicators for verification of the validated production cycles.
Application needs:
- Consistent, repeatable and controlled material transfer process with proven decontamination efficacy for various loads
- Peroxide concentration after cycle not to exceed 1 ppm
- Minimised particulate burden
- 60 minutes or less total cycle time
- Optimised sterilant usage
- Equipment design in accordance with GMP regulations and current GAMP guidelines and overall risk management
- Acceptable footprint and serviceability
- Electronic data security for enabling 21 CFR part 11 compliance
Design considerations
First, a VHP decontamination pass-through system for material transfer is not a material airlock that is simply equipped with a peroxide generator, although the chamber design needs to meet GMP requirements for materials of construction in process contact areas and for cleanability (stainless steel AISI316L or equivalent with surface finish of Ra 0.6 µm or better).
Process and equipment design principles should be equal to a piece of sterilisation equipment. Main purpose of the equipment is to ensure that the bio-decontamination result is achieved on all intended surfaces. Cycle pre-conditioning is required to remove as much moisture from chamber air as feasible (typically down to 6-10 % RH) to allow for sufficient hydrogen peroxide concentration to be reached. This is achieved by utilizing an efficient air-drying system. Relative humidity during decontamination exposure phase must not exceed 99% RH to avoid peroxide condensation.
A strong turbulent airflow pattern with access to all surfaces from top to bottom is required for desired results. An internal chamber fan meets this design criteria well, and has proven to be most efficient in larger steam/air mix sterilizer designs for decades already. VHP vapour must have non-restricted access to all surfaces.
Optimal VHP amount can be ensured by using a combined humidity/VHP sensor as process controller instead of injecting pre-defined amounts of peroxide based on cycle development. Continuous control ensures consistency, and only the required amount of VHP is injected. Doubling VHP amount does not improve kill efficacy, but prolongs the aeration time and total cycle time, subjecting the load to more sterilant than necessary.
A closed loop design with HEPA filter and integral catalytic converter eliminates any need for connecting the equipment to HVAC system – as well as any HVAC system validation concerns (figure 1). Maintaining negative pressure during unloading, and applying active door seal for tightness, are important. A smoke test is easy to pass, but passing the ISO 10648-2 leak test requires improved design for tightness and adds to safety from a risk management perspective. A closed loop, strong airflow circulation with a HEPA filter can be utilised for capturing particles in the beginning and at the end of the cycle by implementing a particle level monitor, setting a particle level target and controlling the process performance.
Minimising equipment footprint by placing the mechanical area on top of the chamber can compromise serviceability. Therefore, side access design might be a better alternative. Meeting 21 CFR Part 11 requirements can be achieved by using a control system design that provides a continuous audit trail and batch recording with similar performance as a GMP steam steriliser – since a VHP material transfer decontamination chamber is used exactly in the same barrier and for the same purpose.