Step By Step Selection Of Cleanroom Disinfectants

Maintaining the cleanliness of a pharmaceutical manufacturing clean room is critical if the products being manufactured are not to be compromised and batches lost.

The choice of disinfectants (alcohols, biocides and sporicides) for contamination control in these controlled areas is a crucial decision, so here is a step by step guide to assist you with making this selection.

How To Choose A Disinfectant:

The disinfectants chosen must be able to maintain the low levels of microbial contamination pre-defined for each class of cleanroom, according to EU standards.

Table 1: GMP Recommended Limits For Microbial Contamination

Contamination could consist of bacteria, fungi, viruses or bacterial spores. Many disinfectants have a broad spectrum of activity especially against bacteria. However, most are not effective against spores, which pose a particular threat of contamination and are difficult to kill. Some disinfectants that are effective against spores are so aggressive that they may also be harmful to health or equipment, so choosing the right sporicide is especially important. If the disinfectant is to be used in a Grade A zone (isolator or laminar flow cabinet) then according to GMP it should be sterile.

Step 1 - Create an environmental history

Air and surface testing of an aseptic area is required under cGMP. This information identifies the organisms in key areas such as product contact areas, transfer hatches and the outer surface of isolators.

An environmental survey provides a basic framework for selecting disinfecting agents and a starting point from which to address specific contamination issues, such as the presence of contamination specific to your cleanroom (facility isolates). Ongoing environmental monitoring then provides an early alarm if contamination levels alter and action needs to be taken.

Step 2 - Establish the requirements from a disinfectant

Armed with environmental information, the facility can determine what efficacy is needed and can decide on a suitable regime. This should ideally include a rotation of at least two disinfectants. If facility isolates include spores, then a sporicide is essential. Other points to be considered might include: Safety - many disinfectants are toxic or irritant and unpleasant for staff to use. Action time to achieve required kill rate - this can vary from minutes to hours.

• Range of formats available - for example ready-to-use, concentrates, impregnated wipes and so on, so that the most convenient and effective method of cleaning can be used.
• Guaranteed sterility - cGMP states that "disinfectants in Grade A and B cleanrooms should be sterile prior to use". For products not used in a single session, sterility needs to be maintained once the product is in use.
• Price - always a key factor, but the calculation of cost needs to include not just the price of the disinfectant, but also costs such as time preparing or applying the disinfectant, protective clothing, wastage, removal of residues, etc.

Step 3 - Select the disinfectants

Traditionally, disinfectants based on phenols and aldehydes have been used, but both these chemicals have disadvantages compared with the latest disinfectants. Phenols are toxic and are not effective against bacterial spores so an additional disinfectant would be required.

Aldehydes are extremely aggressive and are therefore effective against all micro-organisms, but are also highly toxic and require a long contact time for sporicidal activity. Some countries have banned or restricted the use of phenols and aldehydes.

Table 2: Comparison of disinfectants

There is a wide range of other options available. A recent survey showed that alcohol, usually at 70% dilution with water, is a widely used product for disinfection purposes. This is due to its efficacy against vegetative bacteria, its rapid drying time and the fact that it leaves no residues. However, it is not effective against bacterial spores so it needs to be used in rotation with an effective sporicide.

It is also not suitable for use in large areas due to the operator exposure limits and flammability risk. Klercide-CR Biocide B is an alcohol-free blend of a quaternary ammonium compound and stabilised chlorine dioxide. It is non-toxic and non-corrosive, with low odour and a contact time of just five minutes. Its efficacy against spores is suitable for almost all environments, so it presents an ideal solution in many applications.

Step 4 - Testing

The manufacturer of the disinfectant should provide full independent test and validation data against the standard test methods. Initially, check the manufacturer's supporting data for your selected agents, including sporicidal activity, as this will identify any additional testing that is required.

Step 5 - Application

Surfaces must be free of dust and physical soiling prior to disinfection, so that the disinfectant will come into contact with any micro-organisms that are present. A sterile neutral detergent is the ideal product for this task.

Due to the effect of biofilms, surface wiping is recommended to assist in the removal of micro-organisms.

A wide range of formats is available for the application of a disinfectant, including:

• Concentrates for use with a mop and bucket system on large areas
• Impregnated mop wipes as an environmentally friendly alternative to the mop and bucket system
• Ready-to-use sprays
• Impregnated pouch wipes for critical areas.

Preventing Spore Contamination From Disinfectants:

In most cases, ready-to-use disinfectants are delivered by either trigger sprays or aerosols. Trigger spray systems offer significant advantages over aerosols. However, there is a problem with some trigger sprays, as contaminated air can be drawn back into the bottle, compromising the sterility of the liquid. Validation work in a licensed pharmacy unit identified that a trigger spray alcohol had become contaminated with fungal spores only 8 hours after opening.

The SteriShield Delivery System resolves this problem, providing a system with the benefits of a trigger spray whilst guaranteeing the integrity of the contents. The design operates as a closed system, preventing air being drawn back into the bottle. All points of entry into the bag, including the dip-tube, are completely sealed, thereby creating the closed system. This system has been independently validated under rigorous conditions to maintain in-use sterility for 6 months.

The patented SteriShield Delivery System is incorporated into all Shield Medicare sterile trigger sprays – both 1 litre and 5 litre – guaranteeing the sterility of our disinfectants during use and eliminating the risk of contamination from the disinfectant.