Microbiological contamination determination

NOTE Compare this with similar problems in CW systems—those of easily and accurately (and at low-cost) determining levels of microbiological contamination. In most CW systems, apart from a general maintenance quality indicator, the levels of bulk water planktonic organisms tend to have little relevance to sessile organism-biofilm reactions occurring at the metal-water interface. 

Waterside problems that lead to decreases in efficiency and material deterioration can be caused by a variety of mechanisms, such as electrochemical corrosion and deposition of foulants. These problems can be exacerbated by low flow, poor operational practice, process contamination, or specific stresses. It is also important to try to determine cause and effect relationships in order to provide a logical and practical water treatment solution. Such a solution will usually involve some form of cleaning, plus a combined engineering and chemical action plan. Inspection may be made easier by the use of a Boroscope or similar optical/video recording device. The color, texture, and quantity of all deposits should be noted, measurements of pits taken, and microbiological contaminants analyzed. It may be useful to conduct biocide efficiency tests on bacterial slimes. The period when a heat exchanger is open for inspection may be an opportune time for the permanent installation of ports for corrosion-monitoring probes. 

The determination of thermal resistances is technically complex and requires special equipment (BIER Vessels). Since it is unlikely that Bacillus spp. can be excluded from any survey of microbiological contamination, it is reasonable to assume that spores with Di2i-values on the order of 0.3 min will be isolated. Using this figure, SALs of 10 can be calculated at 121°C for 2.4min for bioburdens of 10, and at 121 °C for 1.8 min for bioburdens of one micro-organism per item. 

In general, the cause of any deterioration in process or environmental control can be traced to one of three principle systems a) personnel controls b) process controls or c) facility (engineering) controls. Increases in detected airborne microbiologic contamination levels may result from any of several conditions, and a simple set of logical challenges can be applied to the data to determine the most likely cause. 

Any treatment, such as fumigation, used to reduce fungal or microbiological contamination or other infestation, together with methods of determining the extent of such contamination and potential residues, should be documented. Instructions on the conduct of such procedures should be available and should include details of the process, tests and allowable limits for residues together with specifications for apparatus used. 

Cleanrooms and related areas should be monitored at planned intervals for microbiological contamination using one or more of air sampling, settle plates and surface sampling techniques and the results obtained used to determine action levels. 

The shelf life of reconstituted parenterals prepared in the hospital pharmacy is to be determined by the responsible pharmacist (see Sect. 22.6). When Ucensed injection fluids are reconstituted and prepared for individual patients the shelf life is determined by evaluation of the physico-chemical stability and risk of microbiological contamination. Shelf life depends from a microbiological viewpoint on the risks associated with aseptic preparation and the results of validation studies performed under the pharmacy s specified aseptic preparation cmiditions (see Sect. 31.3.6). 

As to the shelf life from a microbiological viewpoint reference is made to chapter Aseptic handling (Sect. 31.3.6). A system is given for determination of microbiological shelf life in relation to the risk of microbiological contamination at aseptic handling. 

Thus a great deal of pharmacy preparations will have a shelf life after opening that is shorter than in the intact package, for two main reasons. A relatively large part of pharmacy preparations are vulnerable to microbiological contamination, and caution in determining the shelf life is the consequence of the often limited amount of research on this subject. 

Because products that require sterilisation are often aqueous solutions, the initial microbiological contamination can easily be determined in the quality control laboratory by the membrane filtration method (see Sect. 19.6.3). 

A recently published book provides an excellent survey of issues that relate to contamination with endotoxins (present in both viable and nonviable bacteria), their released cell wall constituents, and also viable bacteria in the pharmaceutical industry [1]. It is important to know both the content of the work environment (e.g., indoor air) and the pharmaceutical products themselves. The former provides information on possible sources of microbial contamination and the latter the purity of the final commercial product (or precursors in various stages in its preparation). In some cases it is vital to know the actual bacterial species involved in contamination culture-based methods are standard microbiological techniques which were the focus of Jimenez [1] and thus will not be discussed further. Any contamination (e.g., with endotoxins), regardless of the species of origin, is of utmost of importance (e.g., in determining the safety of a batch of antibiotics to be administered intravenously). This is determined optimally by non-culture-based methods. 

Watwood, M. E., White, C. S. Dahm, C. N. (1991). Methodological modifications for accurate and efficient determination of contaminant biodegradation in unsaturated calcareous soils. Applied and Environmental Microbiology, 57(3), 717-20. 

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