Uses and Limitations of Disinfectants in Secondary Pharmaceutical Facilities

With such a wide range of available disinfectant agents it is not surprising that they have different effectiveness and are used in different locations depending on their properties. Several factors can affect the effectiveness of the agent, including

a) Dilution

specific concentrations are usually needed. Higher concentrations are NOT always more effective. The suppliers recommendations should be followed unless otherwise justified. The suppliers data on effectiveness will relate only to recommended dilutions.

b) Level of contamination both microbially and in terms of organic material and dirt

c) pH and different types of disinfectant have different optimum pH ranges

d) Temperature ñ generally higher temperatures increase efficacy (though some agents are not suitable for use at elevated temperatures e.g. hypochlorite)

e) Hardness of water/metals ñ a number of disinfectants are reduced in efficacy by the presence of metal ions or hard water

f) Formulation ñ alcohol bases may be very effective for many (though not all) disinfectants. Solubilizing agents, chelating agents and buffers may all increase the efficacy. There are a number of factors affecting the selection of the disinfectant, as indicated, but it has been found that the different categories can be given a typical range of uses. Residual effects of disinfectants after cleaning, in preventing growth can be beneficial.

a) Alcohols. Used in hand disinfectants and for product contact parts, often as a spray. The use on machine parts may be for drying (removal of traces of water) as well as bactericidal properties. Typical concentrations of 70% solution in water has some danger due to flammable properties requiring care near machinery/electric supply/flames. The major advantage of alcohol, as well as its very effective bactericidal properties for vegetative
cells, is that it leaves no residue and is easily removed making it ideal for product contact items. It is not sporicidal. Alcohol is may be used as a base for other disinfectants.

b) Phenolics. These agents are most commonly used for disinfection of floors and worktops. They are general pungent smelling and some (such as phenol itself) are hazardous as solids or concentrates, and can cause severe
damage to the skin, may be toxic and are not highly soluble. There are however a wide range of proprietary brands available and their use is widespread for these general disinfectant uses where no product contact is involved and where they are very effective. Other disadvantages include the decrease in efficacy in the presence of organic matter such as rubber, plastic or dirt. Dirty solutions, though still highly pungent, have been known to contain vegetative bacterial cells. The compounds are not sporicidal.

c) Sodium Hypochlorite. The hypochlorite based disinfectants are very widely used for problem areas since they are highly effective against gram negative bacterial and fungi and are reasonably active against spores. It is affected by pH, high pH reducing activity whilst low pH results in loss of available chlorine and it is typically used in solutions at pH range 7 to 9. It has a number of disadvantages which restrict uses, specifically lowered activity in presence of large amounts of organic matter, metals, plastics and light (keep in darkened bottles) and solutions should be freshly prepared. There are also some hazards in its use due to irritant effects on the skin, bleaching effects, with damage on fabrics, and staining damage to some metals. It is not recommended and must not be used as a final treatment for product contact materials due to odor and residues and it is primarily used for problem areas such as changing room/air lock floors, drains, wash bays, sinks, hatches and where its use is specifically required by microbiological monitoring results. It should not be sprayed or used in hot solutions as chlorine, which is the active agent, is readily lost. A more effective agent of the hypochlorite type is Sodium dichloro-isocyanurate (marketed as tablets for making solutions). This material is effective at lower pH than hypochlorite and is less damaging to stainless steel and is more stable. Commercial names are Klorsept and Presept (Jencons/Fison)

Biguanides. The biguanide disinfectants may be used alone or in combination with a number of other disinfectants and are marketed under a wide range of trade names. The most commonly encountered material is Chlorhexidine (usually as the gluconate) which is marketed as Hibicet (with Cetrimide). The products have a wide range of uses as general disinfectants in non product contact situations, both in aqueous solution (often hot for floors and surfaces) and in 70% alcohol for small non-product contact areas on equipment, and hand washing, often as a spray. They are active against bacteria and fungi, particularly gram negative bacteria. They are not sporicidal and proprietary brands often have dyes which may stain surfaces. The detergent properties of the biguanides make them useful in general
cleaning of large areas.

e) Quaternary Ammonium Compounds. Commonly known as QUATS, this is a wide group of compounds having detergent, solubilising and surfaceactive properties as well as disinfectant properties making them particularly useful in Non-Sterile facilities areas. The uses and activity are similar to the biguanides, with which they are often combined, having a somewhat narrower range of effectiveness particularly on gram negative organisms. The relatively low toxicity makes them useful for skin disinfection (e.g. Cetrimide in Hibicet) as well as for floors, surfaces and worktops.

f) Amphoteric agents. They have a broad spectrum of activity against Gram positive and Gram negative Bacteria. They also exhibit anti microbial properties against Yeasts and some Molds. The amphoterics should ideally be used at ambient temperatures. Some agents may form a precipitate at higher temperatures. They can be used for disinfection of floors, walls, work surfaces and equipment. They are available from various suppliers eg. TEGO2000 and TEGO 2001 (TH.Goldschmidt Ltd). The TEGO 2001 brand has improved activity and stability over a wider
temperature range.

g) Aldehydes. The aldehydes have a wide range of activity against fungi and vegetative bacteria and are reasonably effective against spores. The two aldehydes most commonly encountered are Glutaraldehyde and formaldehyde. The later material is considered hazardous, being extremely irritant to the respiratory system and potentially toxic, and the Group recommendation is for its use to be very restricted or eliminated on safety grounds (ref ITS Circular No 131, 1994, see Appendix). Glutaraldehyde has been more acceptable and is more regularly used in a 2% aqueous
solution, whilst it is also a constituent of Tegodor (Diversey Lever) a commercially available agent also containing Formaldehyde and Benzalkonium Chloride. The use of Glutaraldehyde and Tegodor is usually for problem situations such as changing room floors. The material is affected by the number of spores (level of contamination), pH (usually
7.5-8.5 for optimum use) and exposure time which may be as long as 60 mins. The disadvantages are the pungent odour and respiratory irritancy and increasing restrictions on its use by some countries (e.g. USA) on
safety grounds. Another trade name for Glutaraldehyde is Cidex.

h) Hydrogen Peroxide. Hydrogen peroxide is gaining popularity as a disinfectant (or sterilizing agent) in closed situations, such as isolators. It is generated as a vapour (vapour phase is the active agent) although at present these generators are expensive and complex to operate and control. There is also some debate amongst the suppliers of generators on the optimum conditions, particularly humidity and temperature, and mode of action. There is no doubt from the validation of these closed systems that VHP is an effective agent for vegetative bacteria, fungi and spores. It appears maximum efficacy is achieved in closed systems at or close to the condensed point.

The disadvantage of the material is its toxicity in the vapour phase, whilst the advantage is the breakdown of the material to water and oxygen leaving no harmful residues or toxic discharge of vapour. A recent advance in the use of Vapour Phase Hydroxen Peroxide (VHP) has been in room decontamination. This is offered by one supplier and can
be via a mobile distributor which can be located in the room and connected to a generator. For new facilities such a system can be designed into the HVAC although the generator may still be mobile and used for other appliances. Initial work shows such a system to be effective and much quicker and more effective than a formaldehyde gassing.

i) Others: Peracetic acid is used in closed systems as a sterilant and is also available in combination with hydrogen peroxide as a surface disinfectant, where it has sporicidal activity (Spor-Klenz). Although it is considered aggressive and will damage surfaces, there is renewed interest in its use in combined products where safety and toxicity aspects are improved. Peracetic Acid/Hydrogen Peroxide mixes are sometimes used in specific product contact material disinfection (e.g. plastic films and bottles for liquid products) usually in a washing process which is followed by a
thorough rinse to remove traces of the material.