Inspired by nature

What is your idea of an "ideal sporicide" for deployment in cleanrooms and related facilities? And what is on your wish list of the most desirable and undesirable characteristics of the ideal sporicide?

This is the information that was gathered via market research from the various QA/QC peer groups in the pharmaceutical, biotechnology and hospital sectors at the onset of this project. The results of this exercise were used to set the parameters that defined a project designed to bring an "ideal" sporicide to market. These parameters were identified as:

• Measurable performance - CEN 216 via EN 13704 (minimum)
• Intrinsic sterility - Regulatory Guidelines
• Reliability - Validation by design; Reproducibility; Repeatability ; Task/Shift Validity
• Compatibility – Corrosivity; Safe handling & deployment
• Convenience – Shelf life in-stock; Immediacy; No skilled preparations for use
• Economy – Zero capital cost/services cost; Effective unit cost; Task optimised pack size; Minimal wastage

Possible chemistries

Sporicidal agents effectively belong mechanistically to one of three groups of materials. Some debate persists surrounding certain other proposed chemistries but a simplistic grouping remains convenient and essentially sound:

Aldehydes – Typified by formalin and glutaraldehyde, these are effective sporicides but lengthy contact times are often required, and degenerative aging of solutions can be problematic. They are highly reactive and solvent compounds that normally require activation by the addition of trigger compounds such as methanol. Aldehydes present very real hazards to occupational health via dermal and respiratory routes.

Peroxy compounds – This group includes gaseous and solvated preparations of ozone, hydrogen peroxide, various inorganic peroxy salts and peroxyacids. All are highly reactive oxidising agents, intrinsically unstable and corrosive in degree. Many are generated at point of use by chemical or electrochemical devices. Stability and the reliability of stored solutions is suspect, requiring periodic revalidation at point of use.

Peroxyacetic acid is the most widely used member of this group but is highly ionised in solution, corrosive and proves difficult to moderate. Peroxyacetic acid can be unpleasant to work with in all but its most attenuated states. This limitation is exacerbated by spray application techniques.

Oxy-halide radicals – Chlorine, chlorite, chlorate, hypochlorite, chlorine dioxide, chlorous acid, hypochlorous acid. Much is made of the disinfectant properties of inorganic chlorine compounds and dozens of proprietary products and systems claim a long list of useful outcomes. A detailed study of the various reagents, their equilibria and kinetics lead to a somewhat surprising conclusion:

The active sporicide in every case is most likely to be hypochlorous acid (HOCl). This is precisely the active species identified at the heart of the leucocytes' role as biological assassin in human body fluids – a naturally-selected and unrivalled Clean-In-Place (CIP) system.

Hypochlorous acid is represented as

HOCl ? H+. OCl-,

and is a reaction product, in some part, of each and every one of the various solvation, hydrolysis, redox and condensation reactions claimed in the multiplicity of oxy-chloride sporicidal systems promoted commercially. Analogous processes involving the less familiar halogens bromine and iodine are also feasible.

Researchers have sought to moderate hypochlorite salts by the controlled adjustment of pH, to maximise their sterilant potency. Such practices need critical control and constant validation – rendering them largely unworkable at a practical level. Crucial issues of health and safety are involved in such schemes.

The Agma team has studied and developed the intriguing proposal that a nearly ideal sporicide might result from the optimisation of one or more of these systems in such a way that hypochlorous acid dominates that system while also minimising the usually undesirable and hazardous characteristics of sporicides, such as corrosivity.

It was further postulated that, by careful selection of reagents and appropriate mechanical devices it might be possible to generate such solutions reproducibly, at will, from sterile-irradiated, inert precursors in a low-cost disposable device. Emphasis was therefore placed on freedom from hazardous pre-mixings, optimising effective concentration and speed of action with minimal contact time.

HOCl (undissociated) compares very favourably with both Na+:OCl- and with "activated" glutaraldehyde.

Practical design

The resultant practical sporicidal disinfectant, now marketed as Zyceine utilises the best of the chemistries defined by these studies to generate, at point of use, an optimised fluid in which the principal active species is hypochlorous acid. Both the precursor reagents and the activator are intrinsically stable under substantial (ray flux and are mechanically separated until a simple manipulation brings them together immediately prior to deployment. The precise formulation and mechanics of this new spray design are protected by UK Patent Application No. GB 0713291.3

Corrosivity

A major area of concern that has inhibited the more widespread adoption of sporicides in everyday hygiene practice is the corrosive nature of traditional sporicides. Hence, it was important to study what effects were seen on a variety of familiar construction materials and finishes when they were exposed to active sterile Zyceine solutions. Comparisons were then made with sodium hypochlorite solution at pH 11.5 and with free acetic acid solutions. This study comprised continuous immersion tests, "sandwich" tests and long term, intermittent, sprayed exposure.

The outcome of these tests to date has shown that the corrosivity of Zyceine is substantially lower than that of either alkaline hypochlorite or of free acid systems.

Structural aluminium alloys, stainless steel (316), powder-epoxy coatings and optical ploycarbonate are all unaffected by Zyceine during intermittent exposure and in short/medium term (7 days) immersion testing. The vulnerability of common "mild steel" and passivated zinc/cadmium plating was highlighted in these studies, as was the advice of making detailed periodic inspection where these materials are in use – often protected by plastic or painted films.

Long-term "real time" investigations of corrosivity are continuing since "accelerated" models are inappropriate when working with such highly reactive species. Detailed results and subsequent conclusions will be published upon completion of these studies.