Chlorine dioxide in a stable format

The importance of maintaining the cleanliness of a pharmaceutical cleanroom is well known, and the selection and implementation of a suitable cleaning regime is paramount in ensuring that the integrity of the product manufactured in such areas is not compromised.

Current regulations in the UK stipulate that any disinfectants used to control contamination in Grade A and B cleanrooms must be sterilised prior to use and also dictates that, where disinfectants are used, more than one type should be employed.

Traditionally it has been the norm to rotate different types of disinfectants in a pharmaceutical cleanroom, in an attempt to try and avoid any build up of microbial resistance to any one chemical substance or bactericide. However, more recently the industry standard has moved towards using a disinfectant and a sporicide, following a set routine of rotation between the two.

The use of the sporicide is required as the routine disinfectants often have very limited sporicidal action and may not be effective against some spore forming bacteria, such as Bacillus subtilis.

There are several criteria which should be taken into account when selecting a disinfection regime for use in pharmaceutical cleanrooms.

Health & safety

Safety of operatives is always an important consideration in the selection of antimicrobial products and should be at the forefront of any decision taken to use a particular product. Many disinfectants can cause harm if used incorrectly and, wherever possible, hazards should be eliminated or minimised.

Prior to selection the following points should be considered:

• Does the material pose any risk to human health, either in the neat or diluted form – damage to skin, damage to eyes, harmful by inhalation?
• If the material is to be diluted, what is the likelihood of this being done incorrectly? and what are the consequences of this, e.g. release of poisonous gas, or corrosive working solution?
• What is the microbial efficacy and required contact time?

The most relevant and commonly used EN tests for disinfectants for the pharmaceutical industry are:

• EN 1276 - A suspension test that assesses the product’s bactericidal activity.
• EN 1650 - A suspension test that assesses a product’s microbiological effectiveness against yeasts and moulds.
• EN 13704 - A suspension test to assess a product’s sporicidal activity.
• EN 13697- A surface test to assess the product’s activity against bacteria, yeast and moulds on specific surfaces. This test was designed specifically for products used on hard surfaces to give a realistic test that takes into account in use conditions.

Surface compatibility

As cleanrooms are disinfected and cleaned on a regular basis, it is likely that they will be exposed to very large volumes of cleaning solutions over their lifetime. It is, therefore, essential that any product used to clean or disinfect a cleanroom is compatible with and does not damage the surfaces to which it is applied. If the surfaces in the cleanroom become broken, pitted, or damaged as a result of the cleaning and disinfection programme being employed it will not only be very costly to repair and replace but will also compromise the integrity of the surface and make them far more difficult to disinfect leading to possible product contamination.

Taking into account the three factors above the ideal products for cleanroom disinfection would be two rotational biocides, one of which passes EN13704, and both of which have other relevant EN certification with as short a contact time as possible. They should also pose little risk to human health and should not damage the surfaces to be cleaned.

The most common disinfectant options available in the market are:

Peracetic acid and hydrogen peroxide blend: This option gives excellent antimicrobial action, including sporicidal activity; however it has potential health and safety drawbacks and gives off a very strong smelling vapour. It may also cause damage to many metal surfaces.

Amphoteric-based disinfectant: This type of disinfectant poses little hazard to both human health and the surfaces to which it is to be applied. These formulations also tend to give good general antimicrobial activity but the sporicidal nature of the formulations is very limited.

Quaternary ammonium compounds: These types of chemicals give good general antimicrobial action but have little or no sporicidal activity. They generally cause little hazard to human health and are safe to use on most surfaces.

Biguanide-based disinfectants: Biguanide-based disinfectants have good general antimicrobial properties, however sporicidal activity is very poor. They are also incompatible with many substances and can produce staining on surfaces.

Formaldehyde/glutaraldehyde-based formulations: These types of chemical give good antimicrobial activity, but can be very hazardous to human health and are being used less and less frequently.

On a review of the most commonly used disinfectants in pharmaceutical cleanrooms, it becomes apparent that the products available with sporicidal action have drawbacks, either in terms of contact time or health and safety and surface compatibility. There is, however, a new sterile option available called ClearKlens Bi-Spore which is designed specifically for pharmaceutical cleanrooms which meets all of the criteria.

It is system based on generating chlorine dioxide in solution using an activator and base, which are packaged together in single dose bottles to be diluted into water. This method reduces any risk of incorrect dilution. The working solution generated by the activator and base system also gives excellent antimicrobial – including sporicidal activity – and passes EN13704 in 5 minutes. Neither the activator, base nor working solution pose any risk to human health and the solutions are compatible with all surfaces which will be encountered in the cleanroom environment.

Chlorine dioxide has been recognised for its disinfection properties for well over 100 years and has been used since the 1950s for several applications, including the treatment of drinking water. Today, it has many uses worldwide including:

• The sanitisation of food equipment
• Controlling levels of Legionella in cooling towers
• Sterilisation of hospital equipment.

Chlorine dioxide has a broad spectrum of activity against bacteria, viruses, fungi and spores by causing lysis. Although chlorine dioxide attacks the cell walls of micro-organisms, it will not attack human cells due to their different chemical structure. Neither chlorine dioxide nor its reduced form chlorite is classed as hazardous to human health in aqueous solutions, making it a safe option to use.

Chlorine dioxide dissolved in water is completely biodegradable and can be disposed of into normal foul drains. Unlike most other chlorinated products, chlorine dioxide does not produce free chlorine and hence cannot form environmentally-harmful chlorinated compounds often associated with the use of chlorine in the presence of organic molecules.

When independently tested ClearKlens Bi-Spore passes EN13704 with a contact time of 5 minutes, meaning that the extended contact time needed to ensure sporicidal-activity is eliminated. This result, combined with the low hazard to human health and the compatibility with different surfaces encountered in cleanroom environments, makes a chlorine dioxide generating system such as ClearKlens Bispore an ideal sporicidal disinfectant for use in pharmaceutical cleanrooms.