The control of microbial burden on surfaces such as in GMP production areas, R&D animal labs and hospitals is a daily challenge. Many rooms have high ceilings and are equipped with complex equipment, furniture, computers, etc. In practice it turns out that disinfection by wiping is a difficult task under these circumstances.
Photo: Courtesy of Enzler Hygiene AG
Major drawbacks found consist of the following:
- difficult to access surfaces and areas: ceiling, areas behind and under furniture and fixtures
- contact time and pressure applied are highly dependent of personnel
- uniformity of application on all surfaces and reproducibility difficult to obtain and to prove
- laborious and time-consuming
- its validation is very intricate.
Alternatively, airborne disinfection by means of nebulisation techniques allows overcoming many critical aspects of wiping in both procedure and validation. Moreover, the use of hydrogen peroxide (H2O2) with moderate concentration resolves remaining reservations as to toxicity, corrosion, and persistence. H2O2 decomposes into water (H2O) and oxygen (O2) over time and does not leave residues.
Requirements for VH2O2 generation equipment and the biocide
Airborne disinfection is carried out with two elements: the biocide solution and the generator to produce its vaporisation. Solidfog generators are based on micro-nebulisation technology, consisting in the atomisation of a liquid when submitted to high pressure, which converts into vapour until saturation under normal environmental conditions. The composition, design and combination of both elements have to proof its efficacy for a specific application such as the decontamination of a cleanroom.
The main requirements to approach an airborne disinfection are:
- flexibility: applicable for small and large rooms/volumes (scalable)
- minimal requirements as to environmental conditions (temperature, humidity)
- quick install: either mobile or fix-installed equipment
- safe use for personnel: non-hazardous, low toxicity
- non-corrosive chemical, non-persistent
- ease of clearing after fumigation, fast operability
- no residues, harmless by-products from decomposition, no need for neutralization
- broad inactivation spectrum (bacteria, virus, yeast, molds)
- high inactivation rate (kill rate) and efficiency
- simple and reliable qualification method for efficiency
- validated process, fast and robust
- can be used while working in adjacent rooms (providing AHU allow for it).
Decontamination process technology
All these requirements are properly considered and technically solved by Solidfog.
Solidfog has more than 10 years’ experience in providing H2O2 airborne decontamination systems for the pharmaceutical industry with a successful track record behind. Our nebulisation technology ensures a uniform and reproducible distribution of the H2O2 throughout the whole room. Thanks to the design of the spray nozzle, the precision of the biocide priming pump and control over the air pressure provided by our design, we ensure a robust and consistent aerosol supply. Studies conducted by the company with laser diffraction particle analysis have demonstrated a median droplet size of 10 µm. This size is ideal for a quick dispersion and an effective vaporisation till saturation point.
In principle, a decontamination process carried out in normal environmental conditions can be rendered without the need of preconditioning phase regarding temperature and humidity. However, these are factors to be considered during cycle development and validation. Studies conducted by an important pharmaceutical company showed that RH conditions between 40-70% and temperatures between 17-27°C can be properly validated to 6-log reduction by adjusting H2O2 initial liquid concentration. The cycle development strategy should consider the worst case situation and try to fix the concentration of H2O2 for simplifying validation. Solidfog typically recommends a dilution with 12%, which renders the best compromise between sporicidal efficiency and compatibility with materials used in these areas. For such concentration, the ideal starting conditions are 40% RH and 20°C but other starting conditions can be challenged as the results are also influenced by other factors like the overall volume, the related surfaces to be treated and the geometry of the area. Microbiologist have reported in some cases for killing certain virus or bacteria is more convenient a higher humidity, providing a higher level of micro-condensation. In conclusion, there’s not a fixed rule to be followed and only after a case analysis and a job of cycle development (cycle trials), it will be possible to determine the cycle parameters to be validated.
Solidfog has the process experience and know-how to offer this support to the customer. According to specific limitations in terms of environmental and architecture conditions, Solidfog shall recommend the number and position of spray nozzles, the orientation within the room, the pressure into the spray nozzle, the quantity and concentration of disinfectant, the length of exposure time, etc.
Solidfog solutions for cleanroom decontamination
Solidfog has developed a range of equipment in order to better solve different cases and customer needs.
DosyMist® mobile “plug-and-play” unit that can cover up to 200 m3
DosyMistXL® mobile “plug-and-play” unit that can cover up to 750 m3
DosyMistDS® deployed system for specific applications like a pass-box or Material Air Lock (MAL)
DosyMistCS® fixed centralised system by means of spray heads installed in rooms connected to a central unit installed in a technical area.
NeutraMist® catalytic system in order to decrease the aeration phase, which is typically the longer of the cycle.
The approach towards cleanroom disinfection starts with the collection of different data:
- Cleanroom area architecture (layout) with identification of equipment and furniture
- Overall volume
- Defining areas with common AHU that need to be decontaminated together
- HVAC system design and performance (Air Changes per Hour)
- Frequency of decontaminations per area and expected lead times
- Expected log-reduction
- Confirmation that cleanroom panels (especially painting) are prepared to be processed with H2O2. This should be confirmed by the supplier of the panels.
- Information about the typical environmental conditions (Relative Humidity and Temperature) and peak levels along the different year’s season, as they influence the performance of the decontamination cycle.
- Information about the cleaning or disinfecting procedures performed before the decontamination. Traces over the surfaces could lead to chemical reactions and produce corrosion problems.
- Information about specific hots or cold spots or surfaces (e.g. autoclaves, freeze-dryers, piping, etc.) that could have an adverse effect over H2O2 decontamination or produce too much condensation.
Based on this information, we shall come back with a proposal as a first approach including:
- Position and number of units as well as the direction of the spray heads according to layout and internal elements (machinery, furniture, etc.)
- Quantity of biocide based on a fixed concentration of H2O2.
- Estimation of cycle phase lead times (conditioning and contact phase) as per targeted log reduction. However, these values will always be an estimate. Lead times are highly dependent on the adsorption capacity of materials remaining in the room (i.e. filters), the concentration of H2O2, the architecture and the performance of air renewal provided by the HVAC system, etc.
Cycle development and Validation
The definition of cycle parameter values (quantity of biocide, injection rates, pressure, etc.) of the equipment for a certain application (Room, MAL, etc.) will be based on Solidfog’s experience. As said before, this must be defined on a case by case basis and according to specific environmental conditions and the other above mentioned information. Furthermore, these values render a cycle that must be tested and duly validated. The purpose of cycle development is to find a good compromise between effective and assured decontamination, consumption of biocide and cycle lead times (especially in regards of exposure and aeration), challenging the system on worst case conditions. Typically, these tests are initially performed using chemical indicators in first instance. Right after making some adjustments, you can proceed with enzyme indicators and/or tri-scale biological indicators to know the level of log-reduction.
Figure: The profile of a VH2O2 biodecontamination cycle by fogging. The conditioning phase does not require any type of dehumidification. The contact phase begins when the saturation point is reached and therefore the appropriate micro-condensation level occurs. The aeration phase consists of renewing the air and the speed depends on the air extraction system of the area or room.
Validation is the last step and it should be carried out only after cycle development has been successfully finished. In case the BIs give strange results, it is 3 units per position as proactive measure to ensure they are not due to wrong handling or the use of rogue biological indicators. Some of the samples must be placed at the most difficult access points to ensure that there is no contamination risk. Once the results show no growth, the parameters of the cycle are established in the equipment in order to ensure reproducibility. These are: the quantity of biocide, the pressure of injection and the flow rate. Position and direction of the spray nozzles have to be observed too. So in order to ensure the reproducibility of the cycle, it is paramount that the equipment provides internal monitoring and recording systems, as it is in the case of Solidfog.