Bioquell's latest white paper considers environmental monitoring and contamination control strategies that use the benchmark hydrogen peroxide vapour (HPV) gaseous bio-decontamination process.
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'.
Conventional bio-decontamination of cleanrooms and support areas involves manual processes using suspension test-validated disinfectant agents.
However, these agents are not generally validated in-situ with industry standard biological challenges.
This makes it difficult to verify any log reductions in bioburden following the bio-decontamination process.
Additionally, the lack of a process for the controlled removal of the disinfectant agent residue can result in ongoing material damage.
Without active removal, surfaces can be left 'wetted' with aggressive, high efficacy, high concentration, broad spectrum sporicidal agents.
There may also be increased resistance to low-efficacy disinfectants, providing the need to use rotated agents including the periodic use of a general sporicidal agent.
Sampling to identify the bio-burden contamination levels can also be fraught with errors.
There can be poor recovery rates and samples may only represent a fraction of the actual environment and operational time.
There is also an increasing awareness that a significant percentage of the bio-burden may be viable but non-culturable organisms.
These may have been subject to environmental and nutritional stress at the time of monitoring.
It should be recognised that environmental monitoring results of zero CFU do not necessarily mean absence of contamination; it merely means that the bio-burden was below the level of detection at the monitoring location and at the point of sampling.
Contamination is unlikely to be homogenously distributed.
Without qualification, conventional bio-decontamination processes, typically called sanitisation, require significant environmental monitoring to measure the impact on bio-contamination control.
Such processes and monitoring strategies, using 'alert' and 'action' levels, are now under review.
These reviews are challenging the efficiency to control and detect bio-contamination for contamination risk reduction.
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' needs to be demonstrated through log reductions in the biological contamination to pre-defined target levels.
Scientifically, it is impossible to demonstrate a cleanroom or controlled environment is 'sterile', a term that has a simple definition, but is complex in application within pharmaceutical and biopharmaceutical manufacturing environments.
However, if an environment is characterised in terms of microbiological profile and contamination rates under operational conditions, then this control state can be monitored for excursion.
The key is achieving and identifying a characterised control state that presents an acceptable risk of bio-contamination.
Hydrogen peroxide vapour (HPV) decontamination technology, originally used in isolator barriers, has developed a wider application.
It is used in Restricted Access Barrier Systems (RABS) and in cleanroom/controlled areas.
It is likely that as microbiological monitoring technology develops with improved recovery rates, rapid, or real-time detection, then excursions from current 'alert levels' will result in far more 'excursion data' and increased investigations than previously recorded.
More evidence of 'actual' contamination will present a new challenge in risk reduction.
The level of biological decontamination is specified in terms of sporicidal log reduction; typically six-log for critical areas/surfaces and fo7ur-log for surrounding environments.
Decontamination assurance is provided by processes based on sound science, with automated control and monitoring of critical control points.
The HPV process can be validated with Geobacillus stearothermophilus biological indicators1 to routinely achieve six-log sporicidal reduction at room scale.
Biological indicators are an industry standard method used to validate steam sterilisers/autoclaves.
The gaseous vapour phase decontamination process, using hydrogen peroxide under specified conditions, has been accepted by international regulators as a method of achieving surface sterilisation.
Most importantly the HPV process is not wet when compared with manual disinfection.
In the optimised process vaporised hydrogen peroxide molecules are only delivered to surfaces past dew point, at a sub-visible and effective level (2-6um thickness) and controlled removal leaves surfaces residue-free.
The contact time of the active HPV (at sub-visible 2-6um thickness), 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.
In cleanroom facilities, a rare 'oxygen bubble' effect can sometimes be observed.
Some poor-quality painted or coated surfaces that are porous and have a low bond to the substrate allow hydrogen peroxide to pass through.
With the breakdown in contact between the surface and the substrate, oxygen bubbles lift the surface coating.
This is not a chemical attack and such poor-quality surfaces should have no place in a pharmaceutical facility.
However, if 'lifting' is found to occur, proper 'bonded coat' repairs are required.
This issue is easy to manage and any negative effect is far out weighed by the advantages of a thorough and measurable bio-decontamination process.
First, HPV is introduced, leading to an initial rapid increase in HPV concentration.
Once HPV saturation/dew point is achieved there begins the onset of rapid bio-decontamination.
Next, the HPV gassing plateau occurs, which is sustained micro-condensation effecting bio-deactivation.
There is then a Dwell period.
Finally, Aeration occurs - which is the removal of HPV from the atmosphere, typically by catalytic conversion to water vapour and oxygen, leaving no residues.
The rest of this white paper can be found on the company's website.
