Preparation and Control of Disinfectants in Secondary Pharmaceutical Facilities

The importance of control of disinfectants approval of incoming materials and preparation of solutions to be
controlled. The effectiveness of the various disinfectants can be significantly decreased if their preparation as solutions and subsequent control is not properly performed. The issues which should be considered are:

a) Correct dilution of the disinfectant
b) Use of adequately controlled diluents
c) Sufficient pre cleaning of the area to be disinfected
d) Use of the appropriate disinfectant for the purpose
e) Control of the diluted disinfectant with batch numbering and expiry dates
f) Rotation of disinfectants
g) Microbiological environmental evaluation and validation
h) Prepared to SOPs using a batch sheet or document to record details such as batch numbers, dilutions, quantities and expiry dates.

The points which should be considered for each of these issues are:

a) Dilution. The correct dilution of the disinfectant should be made up either in accordance with the manufacturers instructions for proprietary materials, or to guidance given in internal company or external references to ensure optimum activity for the purpose. The use of concentrations above the recommendations does not ensure better efficiency and may be less effective.

b) Diluents. The most widely used solvent is obviously water. The quality of water used to prepare disinfectant solution is important for a variety of reasons. The water must be of a low microbiological content (e.g. <50 cfu/ml) since the disinfectants used are not always effective against a full range of bacteria and many are not sporicidal. Contaminated disinfectant solutions have been a source of problems in the past, being an efficient way of spreading contamination rather than controlling microbiological contamination. If microbiological levels are a problem, the solutions may be membrane filtered (typically 0.2µ) immediately after manufacture to remove the contamination. This should be seen as a temporary measure until water quality is improved, except where the disinfectant is key, in a sterile manufacturing facility or in a microbiology laboratory, where filtration is always required. Potable water (provided it is of good microbiological quality) is frequently used to make up disinfectant solutions but in areas of
hard water, high organic content or high metal content, it may be necessary to use softened, treated water since metal ions and organic content will affect the efficacy of disinfectants.

The other commonly used diluents are alcohols, most commonly ethanol or IMS but also Isopropyl alcohol. The advantage of these alcoholic solutions is the bactericidal effect of the alcohol (at 70% to 80% aqueous solution).
However the hazards of alcohols at this concentration (flammability) make the disinfectant solutions use limited to very specific situations, where only relatively small quantities are needed. Typically these alcoholic solutions
are used in hand washes, for sanitization of equipment and in pass through hatches. Precautions must be taken when preparing and using alcoholic solutions. When preparing disinfectant solutions suitable safety equipment (e.g.
goggles, gloves etc) should be worn, appropriate to the hazards from the concentrate. It is usual practice to add the disinfectant concentrate to the water.

c) Control of Disinfectant Solutions. After preparation, solutions of disinfectants must be controlled. This requires labelling with batch numbering and expiry dates. The expiry date should be established by validation experience. A programme to establish the bioburden at or close to expiry of diluted disinfectant solutions should be in place. This is not needed at a high frequency but should be sufficient to support the routine life of the solution. The disinfectant concentrate should also be identified by manufacturers lot number or a locally applied batch number and an
expiry date applied. There should be an awareness of the possibility of microbiological contamination in disinfectants. Where disinfectants are used for prolonged periods there should be periodic microbiological assessment of the solution. Undiluted disinfectants should be tested on receipt and at 6 month intervals.