Validating Cleanroom Disinfectants

The aim of this article is to examine the scope of validations to achieve a smooth and successful outcome. As a disinfectant manufacturer, we have a unique perspective on validation because we operate cleanrooms and to similar standards. Our perspective includes the pharmaceutical, biotechnology, and medical devices industries, where similar issues arise repeatedly. The message is simple "consider ALL aspects of new agents, right from the start." The result will be quick and meaningful validations allowing early implementation and prompt responses to audits. There are many reasons to validate a new disinfectant; new standards, repeated action points, health and safety, or corrosion problems. Whatever the cause, there are five key points:

What microbiology testing is required?
What is the specification of the agent and how will it be used?
What are the health and safety implications?
What is the impact on the environment?
What support can you expect from the manufacturer?

Microbiology is very important, and you must decide your test objectives. Since a wide range of agents can deal with most cleanroom organisms successfully, the key decision is probably what level of sporicidal activity is required? A log 5 reduction in spores is achievable, but this has other implications. For most cleanroom users, and the draft CEN, a log 3 reduction is usually adequate. Check the manufacturer's supporting data for your selected agents, including V, Nita sporicidal activity, because this will identify any additional testing. Most disinfectants have EN 1276 (bactericidal) and EN I 65() (fungicidal) efficacy data. Good sporicidal evidence is a Log 3 reduction in soiled conditions, for instance, using a modified EN 1276 test and a spore suspension. Reported success with difficult environmental isolates is invaluable. For example the sporicide, Klercide CRTM B has been tested against many organisms, including B. licheniformis, which can cause major problems. A good indicator is the experience of major reference sites. This includes successful action point use; for example, Klercide CR B has been used as the last resort to remove troublesome spores.

Disinfectants

Another excellent source of data is the commissioning of new cleanrooms. After a builder's clean, environmental monitoring identified gross contamination including spores. The suite was cleaned only once with the sporicide Klercide CR B, using a cleanroom mop and double bucket system and almost all organisms were eradicated. This data provides supporting evidence of effectiveness, which helps select the agents for validation. The next step is to determine your sporicidal test requirements, but this can be problematic because isolates can be difficult to sporilate, and neutralisation of the disinfectants is not always straightforward. In response, we have developed a methodology for any disinfectant, whichand can be used by an independent laboratory to give prompt and reliable results. We produced a fully validated membrane test, which enables real situations to be tested, such as spraying onto a surface.
To achieve this, we focused on the following specific areas:

Accurate quantification of the number of organisms to give meaningful log reduction results.
Uniform presentation of spores.
Consistent exposure of the disinfectant to the spores.
Wash phase to ensure full neutralisation.

Two strengths of Klercide CR B (5% at 20%) were compared with peroxide/peracetic at two independent laboratories. The results were remarkably consistent, even in soiled conditions. This is worth mentioning because the interfering substance and innoculum diluted the active concentration to only 90%. Whilst the microbiology work is in progress, it is important to widen the scope of the validation and avoid last minute problems. The final specification of the disinfectant must be considered carefully to ensure its can be transferred easily into the cleanroom, and it can meet the required standards, such as sterility, or diluted with Water for Injection. Similarly a disinfectant may need a range of presentations and methods of application for different environments; large areas will require concentrates for use with mop and bucket or fogging, and critical areas will need ready to use sprays. In all cases, the product must be supplied with essential batch documentation. II is also essential to review the intended standard operating procedures to determine the implications a particular biocides may have. Factors such as rotation of biocides can have a major impact on the final outcome.

There can be major operational considerationseffects, for example formaldehyde fogging with a 24 hour turnaround time, or the need to rinse after some agents, will have consequences which cannot be overlooked. Avoiding operator error especially with bulk concentrates, to get the correct dilution, also needs careful thought. The instructions for dealing with a spillage can also have an impact. Disinfectants are tested in soiled conditions, but is powerful efficacy the answer? Most procedures recognise that a spillage would be physically removed, before the biocide was required. A final procedure point is; how long can you keep your disinfectant before it must be discarded This has wide implications for wastage and auditors in use shelf life of a product. This especially applies to biocidal sprays, and we have developed the Sterishield Delivery System to preserve the integrity of sterile contents. To demonstrate this, the system was tested using nutrient broth and the results, provide a clear indication that in use life is valid for up to three months. Alongside the effectiveness and usefulness of agents, a health and safety risk assessment is required as part of the validation, because some excellent disinfectants are harmful and are difficult to use in cleanrooms. The occupational exposure limits, the extra protective equipment and cost have to be considered for each agent. Input from the personnel who will use the disinfectants can also prove invaluable in the final selection.

Similarly, practical considerations such as on site storage, and increasingly, the waste disposal of chemicals or packaging materials can have major implications, resulting in additional costs.

Many disinfectants, especially sporicides, are oxidising agents and the environmental impact of using these in cleanrooms containing expensive equipment has to be taken into account. A review of the available corrosion data on materials used in cleanrooms and isolators should be fundamental part of every validation. For instance a thorough testing programme conducted at the University of Wales supports the Klercide range of biocides. Most cleaning agents will leave a residue, but its importance will depend on the area and the operating procedures. In direct product contact areas it will probably involve rinsing and testing, but elsewhere this may not be required. The final element is the cleanroom disinfectants supplier. Auditors may challenge your validations, and much will depend on the qualities of the manufacturer to respond quickly in an everchanging regulatory environment. Check they can provide all the technical support you require, operate to acceptable standards and have the production capacity to meet your demands, both now and in future. To conclude, the scope of validation is very wide, however considering all aspects right from the start,. It will save time and money and enable you to meet the next critical deadline or audit.