Disinfectant Validation

The purpose is to assure that the recommended disinfectant has the acceptable relative standard of the antimicrobial activity using the membrane filtration technique and surface testing technique. 

It is the responsibility of all analysts (microbiologists) to follow the procedure. The quality control (QC) manager is responsible for SOP compliance. 

The membrane filtration technique is used once, prior to the introduction of a new disinfectant within the production department. The surface testing technique is used prior to any changes in the recommended procedure for evaluating its effectiveness on surfaces to be treated and demonstrating activity against contamination for various contact times. 

Sterile distilled water Sterile screw-cap test tubes Sterile buffer (dilution blanks) 

Poured, sterile soybean casein digest agar (SCDA) petri plates Poured, sterile potato dextrose agar (PDA) 

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All disinfection and sterilization processes for equipment should be validated, for preference using a microbiological challenge with an organism of appropriate resistance to the disinfectant, sterilant or sterilizing conditions. Once the required log reduction of the challenge organism has been achieved, physical and/or chemical parameters can be set which form the critical control points for the process. 

Stainless steel disks are contaminated with a bacterial test suspension and dried. The disinfectant is applied on the dried film on the disk and kept at a specified temperature for a defined time. The disk is than transferred to a previously validated neutralization medium to stop the action of the disinfectant. The cfii of surviving bacteria recovered from the surface is determined quantitatively. 

In conclusion, the authors of the cited studies all agree that further research into environmental risk assessment of hospital effluents, incorporating different types of substances used in care and diagnostic activities, as well as cleaning operations (pharmaceuticals, detergents, disinfectants, heavy metals, macropollutants), is vital. Moreover, further studies need to be focussed on evaluating the risk posed by pollutant mixtures, and work is needed to validate the predictive models proposed thus far [19, 49], to evaluate chronic toxicity due to PhCs and then-mixtures and to provide experimental data pertaining to specific case studies. 

Materials used must cleaned and disinfected with the usual cleaning and disinfecting agents. Friction in the transport system must not cause particles. Electric motors without ventilators must be used and the sensors installed must be resistant to the cleaning and disinfecting agents. In general, every process must be reproducible, documented and validated. 

Because GFPuv exhibits stability to extreme conditions such as exposure to heat and chemical denaturants (disinfectants) in a wide pH range, its expression by prokaryotes, followed by extraction and purification, should be studied for its potential utility as a marker in validation procedures. In addition, the protein extracted from E. coli and further purified by hydrophobic interaction chromatography (HIC) resins should be analyzed qualitatively (2) by sodium dodecylsulfate polyacrylamide gel (SDS-PAGE) to define the best purification method. SDS-PAGE with Coomassie or silver staining provides a sensitive method to determine the most appropriate HIC support for the purification of GFPuv. 

Validation of disinfectants should be concentrated on two aspects of their potential to create problems in aseptic manufacture. First, they may themselves be sources of microbiological contamination second, they may not be effective against microbial contaminants. 

Production areas should be designed to permit disinfection between campaigns, using validated methods. 

Equipment used for purification, separation or concentration should be sterilized or disinfected at least between use for different products. The effect of the sterilization methods on the effectiveness and validity of the equipment should be studied in order to determine the life span of the equipment. 

Equipment glassware, the external surfaces of product containers and other such materials must be disinfected before transfer from a contained area using a validated method (see 47 above). Batch documentation can be a particular problem. Only the absolute minimum required to allow operations to GMP standards should enter and leave the area If obviously contaminated, such as by spills or aerosols, or if the organism involved is an exotic, the paperwork must be adequately disinfected through an equipment pass, or the information transferred out by such means as photocopy or fax. 

Careful consideration should be given to the validation of methods for sterilization, disinfection, virus removal and inactivation. 

Disinfection and/or wastes and effluents disposal may be particularly important in the case of manufacture of immunologcial products. Careful consideration should therefore be given to procedures and equipment aiming at avoiding environmental contamination as well as to their validation or qualification. 

For Aseptic Processing where disinfection is employed to further reduce the surface contamination level, the choice of disinfectants and the way that they are used should be described in a procedure, in addition, detergents, disinfectants and antiseptics should be supplied sterile, or be sterile-filtered or otherwise sterilised at the use-dilution, or be sterilised as a concentrate and diluted only with sterile water. Diluted disinfectants or antiseptics should not be stored. Containers should not be topped up. Disinfectants/detergents used should be validated and approved. When disinfectants are used, more than one type should be employed. Monitoring should be undertaken regularly to detect the development of resistant stains. Disinfectants and detergents used in Class 1 and 2 areas should be sterilised prior to use. 

Fogging should not be used as air contaminants are readily dissipated by natural or mechanical ventilation. Fumigation with humidified formaldehyde vapour may be employed to reduce microbiological contamination in places inaccessible to surface disinfection, however if fogging or fumigation is used, the process should be validated. 

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