Antisepsis, Disinfection, and Sterilization. Gerald E. McDonnell
directed flow)
Antimicrobial activity is also greater as the concentration of biocide is increased but also varies depending on the biocide and its application. A notable example is alcohols, where less bacteriocidal activity is observed at concentrations greater than 90% alcohol in water, and the optimal range is actually within 60 to 80%; efficacy is dramatically less at lower concentrations. Further, despite the alcohol concentration, little to no efficacy has been reported against bacterial spores. The optimization of a biocide concentration is an important consideration in various disinfection and sterilization processes. Higher biocide concentrations can lead to unwanted effects, including material incompatibility and safety risks, in particular with gas-based applications. In the case of liquid applications, as discussed in section 1.4.6, the efficacy of a biocide can be dramatically enhanced or reduced by various formulation effects that should also be appreciated. These effects include pH (for biocide efficacy and stability), the quality of water, and the presence of excipients, like surfactants.
The control of relative humidity is an important consideration for many gas-based chemical biocidal processes, including the use of ethylene oxide and formaldehyde. Other effects include the state of the biocide (in liquid or gaseous form) and its delivery (to ensure that all site are contacted). Many physical and chemical sterilization processes are conducted under vacuum (e.g., ethylene oxide and plasma-hydrogen peroxide vapor), in vacuum or pressure cycles (e.g., steam), or under specific directed-flow conditions (with liquids and gases) to optimize the penetration of the biocide to all contact sites within a given load.
1.4.8 The Importance of Cleaning
Cleaning is the removal of contamination from an item to the extent necessary for its further processing and its intended subsequent use. In many applications, it is important to ensure the removal of residues following the use of a reusable surface, for example, to prevent cross-contamination between pharmaceutical manufacturing batches, to reduce the level of bioburden on the surface, and particularly, to ensure that a subsequent biocidal process can be effective. Various surfaces require routine cleaning, including manufacturing vessels, equipment, or areas; food-handling surfaces; and reusable medical, veterinary, and dental devices. The presence of various organic (including lipids, proteins, and carbohydrates) and/or inorganic (including various heavy metals like calcium and iron) soils on these surfaces can often dramatically interfere with the activity of a biocide.
Cleaning is generally achieved by a combination of physical and chemical processes. Physical effects include simple immersion, manual cleaning (brushing and wiping), and automated cleaning. Automated cleaning includes the use of washers (or washer-disinfectors [Fig, 1.27]) and clean-in-place systems. Clean-in-place systems are integral to manufacturing equipment (such as reaction vessels), which can be automatically cleaned without disassembly. Automated washing machines allow the placement of items into the washing chamber for exposure to a cleaning process. They can be used for washing only or as washer-disinfectors, which are used to clean and disinfect (using heat and/or chemicals) devices and other articles. They can consist of single- or multiple-chamber washers and provide physical cleaning by agitation, directed flow, spraying, and ultrasonics (where the items are immersed and exposed to sound waves that aid in the physical removal of soil).
FIGURE 1.27 Examples of single (left)- and multiple (right)-chamber washer and washerdisinfector machines. Washer-disinfectors can come in a variety of shapes and sizes, depending on their required uses.
Chemical cleaning is achieved using various types of cleaning chemistries (Fig. 1.28). Similar to formulation of biocides (see section 1.4.6), cleaning formulations can contain a variety of components that aid in the chemical removal of soils from a surface (Table 1.28). Cleaning chemistries can be classified into various types, including enzymatics and nonenzymatics. Enzymatic formulations contain active enzymes that degrade various organic-soil components over time, including lipases (lipids and oils), proteases (proteins), and amylases (starch and other carbohydrates). Nonenzymatic formulations can be further subclassified into neutral, acidic, and alkaline cleaning formulations. Acid cleaners are particularly used for the removal of scale and mineral deposits, while alkaline cleaners are particularly effective at removing and degrading protein-based soils. Neutral cleaners, depending on their formulations, usually have the widest compatibility with various types of surfaces. In some applications, simpler cleaning chemistries are employed, including alcohol wipes and high-quality water (such as water for injection [see section 5.2]).
FIGURE 1.28 Various types of cleaning chemical formulations.
The choice of physical and chemical cleaning processes depends on the types and levels of soils that are present on a surface. The overall efficacy and efficiency of these processes can be optimized for a given application by consideration of the cleaning contact time, chemical concentration, temperature, and efficiencies of physical effects.
1.4.9 Water Quality
Water is an important component of many antiseptic, disinfectant, and sterilization applications. Typical uses of water include:
Biocidal-product formulation (as a solvent)
Biocidal-product dilution on use (e.g., antiseptics and disinfectants)
Cleaning alone or in combination with cleaning formulations prior to disinfection or sterilization
Pharmaceutical-product preparation (e.g., dilution for injection)
Rinsing to remove residuals following cleaning or disinfection
As a disinfectant (moist heat) or sterilization agent (steam)
Humidification as part of sterilization processes (e.g., with ethylene oxide or formaldehyde)
Steam sterilization
TABLE 1.28 Various components of cleaning formulations
| Ingredient | Purpose |
| Solvent, including water | A solvent is a substance (usually liquid) that is capable of dissolving other substances, water being the most common. Solvents are also used for solubilization of various soil components. |
| Emulsifiers, surfactants | Emulsifiers are ingredients (including surfactants) that allow the formation of stable mixtures (emulsions) of water- and oil-soluble ingredients. Surfactants (“surface-acting agents”) can be used as emulsifiers, but also to reduce surface tension, improve the wettability of a surface, disperse contaminants, and inhibit foam formation. |
| Chelating agents or sequestrants |