Improving efficiency in bio-contamination control and risk mitigation using hydrogen peroxide (H2O2) decontamination processes

There is a need to improve the efficiency in the pharmaceutical industry to meet new challenges of globalisation, competitiveness and the increasing diversity of products. The risk of biological contamination is increasing and, unchecked, is a risk factor for production processes and product quality, with potential damaging consequences on business performance and risks to patient health. This article considers environmental monitoring and contamination control strategies using the benchmark gaseous bio-decontamination process, hydrogen peroxide vapour (HPV).

Bio-contamination control and monitoring

Quality Risk Management (QRM) needs to consider the inefficiencies in microbiological monitoring. The forthcoming revisions to the ISO14698 standard on bio-contamination in cleanrooms and controlled areas and the USP<1116> microbiological control and monitoring of aseptic processing environment chapter, will place more emphasis on 'contamination rates'.

Improving bio-decontamination assurance

As monitoring technology improves, the detection of 'actual' contamination will present new challenges. Improvements in monitoring need to be complemented by improvements in bio-decontamination control. Alongside this, 'decontamination assurance' will need to be demonstrated through log reductions in the biological contamination to pre-defined target levels.

Vaporized hydrogen peroxide can be validated with Geobacillus stearothermophilus biological indicators ¹ to routinely achieve 6-log sporicidal reduction at room scale. Biological indicators are an industry standard method used to validate steam sterilizers/autoclaves. The gaseous vapour phase decontamination process⁴, using hydrogen peroxide under specified conditions, has been accepted by international regulators as a method of achieving 'surface sterilization'.

Bio-decontamination efficacy and material/process compatibility

Most importantly the H₂O₂ process is not wet - compared with manual disinfection. In the optimized process² vaporized hydrogen peroxide molecules are only delivered to surfaces past dew point³, at a sub-visible and effective level (2-6µm thickness). Controlled removal - leaves surfaces 'residue free'.

The contact time of the active HPV (at sub-visible 2-6µm), and the residue-free nature following the aeration cycle, separates the process from a 'wet' condition. HPV also exhibits broad material compatibility and can be successfully used in areas containing sensitive electronics.

Potential efficiency savings using a vaporized H₂O₂  bio-decontamination process

Using the gaseous vapour phase decontamination process, filling lines can be gassed-in-place (GIP) including indirect product contact parts. Such a strategy presents significant efficiency savings and risk mitigation^4. Following commissioning, or re-qualification, with facility shutdowns, cleanrooms can be returned to 'microbiological control' state quickly by deploying a HPV process that can be verified using a biological challenge. Such a process can be deployed as a room bio-decontamination service without the need for capital expenditure. At the restart of a HVAC set back in a cleanroom facility following a quiet or non-operational period, a validated HPV decontamination process can provide evidence for compliance to enable the room to be returned quickly into production. Traditional 'spray and wipe' disinfection transfers for materials entering cleanrooms are now under challenge, as the process is difficult to comprehensively validate. This has led to significant growth in efficient HPV gassed transfer chamber products which provides a more effective and fully validatable bio-decontamination process.

Discussion

The HPV process provides a more 'complete' bio-decontamination. When a high efficacy, automated bio-decontamination process is used (including in-process critical control point monitoring), significantly less microbiological monitoring is justified, limiting sample sites to worst case and high risk locations. The reduction in monitoring reduces the cost and extent of monitoring required in addition to reducing the risk of false positives.

By improving the 'decontamination assurance' using a scientifically validated HPV process then there is inherent improvement in 'sterility assurance'.

NB: for references associated with this article, please see www.ngpharma.eu.com

References: ONLY TO BE USED ON THE WEBSITE, NOT IN HARD COPY

1.     PDA Technical Report No.51 (Dec 2010), Biological Indicators for Gas and Vapor-Phase Decontamination Processes: Specification, Manufacture, Control and Use

2.     Beatriz Unger-Bimczok et al - J Pham Innov (2008) 3;123-133

3.     Watling et al PDA Journal 2002 Vol 56 No.6

4.     Pharmaceutical & Healthcare Sciences Society - PHSS RABS White paper, Sept 2010, including MHRA, FDA review. info@phss.demon.uk

5.     Drinkwater - Impact of QRM on RABS - Cleanroom Technology December 2010