Fumigation: Choose Your Weapon!

Previously in The Medicine Maker, I recognized the challenges of selecting the right fumigant for microbiological safety cabinets, high containment level areas, and cleanrooms (1). I noted my relief that it was no longer my job to choose a new fumigation system (I’m now based on the vendor side), but for the purpose of this article, I am going to put myself back into the shoes of a site fumigation lead and think about how I would approach the task of replacing an existing system.

From a formaldehyde user’s perspective, at the time of writing, we are still waiting for the Biocidal Products Committee to decide whether they will approve or reject its use in the EU Biocidal Product Regulation (EU-BPR) usage classification PT2 category. A decision on formaldehyde usage was originally expected in the summer of 2016 (2), but there is still no news. The British Health and Safety Executive (HSE) document, “Biological agents - The principles, design and operation of Containment Level (CL) 4 facilities” (3), has a whole appendix related to fumigation advice. At the very end of the appendix, it quotes, “Further guidance on the use of alternatives to formaldehyde as a fumigant is currently in preparation and will be available from the HSE website.” The HSE has released nothing yet, so formaldehyde is still the recommended fumigant – backed up by a study from the HSE’s Health and Safety Laboratory (HSL) (4).

Factors to consider

When it comes to choosing your fumigant, there are a number of criteria to consider. Here is my list, based on order of importance:

1. Active substance registered in or exempt from Biocidal Products Regulation (BPR) category PT2
2. Repeatable process
3. Efficacy of the fumigant/biocide
4. Penetration of spills
5. Ease of use
6. Corrosiveness of biocide to fixtures, fittings and equipment
7. Chemical incompatibilities of the fumigant
8. Cost
9. Downtime from fumigation process

As soon as you start looking at a new fumigation system, make sure the active ingredient is registered as a PT2 biocide – or exempt from that classification. Exempt disinfectants (or more precisely the active ingredient) will be registered under the EU Medical Devices Regulations. If it isn’t, then you are breaking the law by using it as a fumigant. If you are not based in the EU, you will need to check what regulations you should be adhering to. Arguably the next two criteria (repeatability and efficacy) are equal in their importance with CL3 and CL4, but in the end whatever fumigation system you choose must be robust – and you must have total confidence that it works every time.

Penetration is very important when decontaminating spillages, and it has been a requirement for many years in the HSE advice – and in many other countries – on the management, design and operation of microbiology labs, with specific advice in appendix 3 (5). Ease of use is vital, as most operators will not perform fumigations on a regular basis; in short, the easier the better. Corrosiveness is a greater issue in areas where there are frequent fumigations. Chemical incompatibilities can be managed by removing or isolating the incompatible chemical. For example, with formaldehyde as the fumigant, any chemical containing chlorine needs to be removed from the area before fumigation begins. The amount of downtime for the fumigation process must be sensible, but isn’t crucial. The cost also has to represent value, and there is often a prudent limit on what can be spent. Notably, most of the cost comes from the setup and validation rather than actual future usage.

There are other factors that will affect the relative importance of the above criteria. For example, choosing a new system for a clean room where pathogens are not handled will mean a number of the above criteria need not be considered at all. Also, in areas where there is no chance of spillages, efficacy in most cases need only be demonstrated against the recommended biological indicator for that biocide, so will come lower down the list. Certainly in the private sector, cost and downtime will be of greater importance, where other factors such as chemical incompatibilities and corrosiveness can be controlled, or are less of an issue because of fumigation infrequency.

Weighing up the options

The basis for my search for an alternative to formaldehyde began with the HSL fumigation study (4), in which hydrogen peroxide (H₂O₂), chlorine dioxide and ozone based fumigation systems were assessed. Starting with H₂O₂, two systems (where H₂O₂ is the active substance) were assessed in the HSL study – either can be provided  as a service offered by the manufacturer, or the equipment can be bought. H₂O₂ is registered as a PT2 biocide so can be legally used as a fumigant (6). The fumigation service is usually a cost-effective solution to users who do not require frequent fumigations and do not have the expertise internally to perform the task in house; however, should you purchase either of the systems assessed in the study, then the initial setup costs are considerable. The amount of H₂O₂ required and the cycle length is calculated by the equipment based on a number of factors such as room volume and pre-conditioning stages.

Both of the assessed H₂O₂ systems have been in use for many years and arguably are the most mature of the formaldehyde alternatives on the market. One system generates a layer of micro-condensation (above the dew point) and the other maintains the vapor level below the dew point. An independent study from the HSE does acknowledge that both H₂O₂ systems frequently gave good results against all pathogens (4).

Chlorine dioxide (ClO₂) is gaining in popularity. Although its anti-microbial properties have long been known (it is commonly used as a disinfectant in other areas), ClO₂ struggled to be accepted initially as a fumigant because of fears over its potential corrosiveness and toxicity. It is not considered a substance of concern by the ECHA, so is exempt from BPR PT2. ClO₂ fumigations are actually not corrosive, but a controlled study by the US EPA showed it can be corrosive inside functioning computers due to the heat from the CPU (7).

The HSL study gives this system the thumbs up in terms of its efficacy and reliability in comparison with formaldehyde against a range of tough-to-kill pathogens and spores. It is also excellent at inactivating beta-lactams and, thus, ideal for decontamination of those facilities (8). The cycle starts with a pre-conditioning step, which increases the humidity in the room to 60-75 percent where ClO₂ is most effective. The humidity is then held for 30 minutes, and then ClO₂ is generated and delivered into the room and controlled at the appropriate level. The final stage is aeration (extraction). It should be noted that the ClO₂ system is operated externally, so any connections to the control system must pass through an aperture into the room. Also, as a true gas system that can penetrate most crevices, you must be able to guarantee sealability of the area to prevent leakage.

Another system to be considered uses hydrogen peroxide/peracetic acid, although not assessed in the HSL study, it has a number of existing customers in the pharmaceutical sector. The proprietary chemical – 22 percent H₂O₂ and 4.5 percent Peracetic acid – which is diluted down for use as a 10 percent solution, claims a broad range of efficacy against all types of microorganisms. The delivery system uses compressed air to pressurize the unit, forcing out ultrafine, atomized droplets into the atmosphere (fogging).

The amount of the chemical to use is easily calculated based on the room volume. Fogging starts as soon as the compressed air is switched on and following a one-hour hold time the fumigant is vented – the whole process takes around 2-5 hours from start to finish. The fast turn-around time is clearly an advantage, but it does leave a slight acetic acid odor after fumigation (which should clear fairly quickly). The other main advantages of this system are that the room humidity does not need to be raised pre-fumigation, so there is little chance of the chemical pooling in cooler areas. It is also considerably cheaper than H₂O₂ systems. My main concern for this system is that the chemical might corrode copper over multiple fumigations. But in cleanrooms with predominantly stainless steel and plastics, this will not be an issue. The proprietary chemical is registered as a medical device and so is exempt from the EU-BPR.

Ozone fumigation systems are another alternative. Although aimed more at the food, water treatment and clinical sectors to reduce bioburden and undesirable microorganisms, such systems were also tested by the HSL study. However, I could not find the system described in the report. Also, although the anti-microbial properties of ozone are well documented (9), I have not found any ozone fumigation system being marketed for the fumigation of laboratories or cleanrooms in the pharmaceutical sector (if you know of any then I’d be interested to know more).

Drawing from the results of his findings, in a presentation to the Annual Biological Safety Conference in 2012 (10), Alan Beswick, principal author of the HSL study, offers advice to both end user and manufacturer. To the end user, he emphasizes the importance of validation, especially against target organisms where high containment laboratories are concerned; to the manufacturer, he asks for both reliability in terms of the consistency of fumigation cycles and technical reliability of the equipment provided. It is sound advice!

Andrew Ramage is Microbiology Product Specialist, at Cherwell Laboratories, Bicester, UK.